8,9-Epoxyeicosatrienoic acid is an epoxyeicosatrienoic acid eicosanoid, a metabolite of arachidonic acid. The P450 epoxyeicosatrienoic acids (EETs) are endogenous lipid mediators produced by P450 epoxygenases and metabolized through multiple pathways including soluble epoxide hydrolase (sEH). The cytochrome P-450 (P450) monooxygenase pathway includes enzymes of the CYP1A, CYP2B, CYP2C, CYP2E, and CYP2J subfamilies that catalyze the formation of four regioisomeric products, 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid. EETs are produced in brain and perform important biological functions, including protection from ischemic injury. Both light flashes and direct glial stimulation produce vasodilatation mediated by EETs. EETs may be involved in the development of hypertension and endothelial dysfunction in DOCA-salt rats, but not in excessive collagen deposition or electrophysiological abnormalities. EETs have vasodilator and natriuretic effect. Blockade of EET formation is associated with salt-sensitive hypertension. Four regioisomeric cis-EET are primary products of arachidonic acid metabolism by cytochrome P450 epoxygenases. Upon hydration by soluble epoxide hydrolase (sEH), EET are metabolized to dihydroxyeicosatrienoic acids (DHET). These hydration products are more stable and less biologically active than EETs. (PMID: 17494091, 17468203, 17434916, 17406062, 17361113, 15581597).


8,9-DiHETrE is a Cytochrome P450 (P450) eicosanoid. Eicosanoids generated from arachidonic acid (AA) metabolism by cytochrome P450 (P450) enzymes are important autocrine and paracrine factors that have diverse biological functions. P450 eicosanoids are involved in the regulation of vascular tone, renal tubular transport, cardiac contractility, cellular proliferation, and inflammation. P450converts AA to 8,9- dihydroxyeicosatrienoic acid. This enzymatic pathway was first described in liver; however, it is now clear that AA can be metabolized by P450 in many tissues including the pituitary gland, eye, kidney, adrenal gland, and blood vessels. (PMID: 17431031, 11700990).


5,6-Epoxy-8,11,14-eicosatrienoic acid is an Epoxyeicosatrienoic acid (EET), a metabolite of arachidonic acid. The epoxyeicosatrienoic acids (EETs) are endogenous lipid mediators produced by P450 epoxygenases and metabolized through multiple pathways including soluble epoxide hydrolase (sEH). The cytochrome P-450 (P450) monooxygenase pathway includes enzymes of the CYP1A, CYP2B, CYP2C, CYP2E, and CYP2J subfamilies that catalyze the formation of four regioisomeric products, 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid. EETs are produced in brain and perform important biological functions, including protection from ischemic injury. Both light flashes and direct glial stimulation produce vasodilatation mediated by EETs. EETs may be involved in the development of hypertension and endothelial dysfunction in DOCA-salt rats, but not in excessive collagen deposition or electrophysiological abnormalities. EETs have vasodilator and natriuretic effect. Blockade of EET formation is associated with salt-sensitive hypertension. (PMID: 17494091, 17468203, 17434916, 17406062, 17361113).


5,6-DHET is an epoxide intermediate in the oxygenation of arachidonic acid by hepatic monooxygenases pathway. 5,6-DHET is the hydrolysis metabolite of cis-5(6)Epoxy-cis-8,11,14-eicosatrienoic acid by epoxide hydrolases. Many drugs, chemicals, and endogenous compounds are oxygenated in mammalian tissues and in some instances reactive and potentially toxic or carcinogenic epoxides are formed. Naturally occurring olefins may also be oxygenated by mammalian enzymes. The most well known are lipoxygenases and microsomal cytochrome P-450-linked monooxygenases. The epoxides may be chemically labile or may be enzymatically hydrolyzed. When arene or olefinic epoxides are formed by microsomal P-450-linked monooxygenases, they are often rapidly converted to less reactive trans-diols through the action of microsomal epoxide hydrolases. (PMID: 6801052, 6548162).


8S-HPETE is metabolized from arachidonic acid by the enzyme 8S-lipoxygenase (8-LOX in mouse, ALOX15 and ALOX15B in human). 8S-HPETE will be readily reduced under physiological circumstances to 8S-hydroxyeicosatetraenoic acid (8S-HETE), a natural agonist of peroxisome proliferator-activated receptor alpha (PPAR alpha). (PMID: 16112079).


19(S)-HETE, also known as 19-hete, belongs to the class of organic compounds known as hydroxyeicosatetraenoic acids. These are eicosanoic acids with an attached hydroxyl group and four CC double bonds. Thus, 19(S)-hete is considered to be an eicosanoid lipid molecule. 19(S)-HETE is considered to be a practically insoluble (in water) and relatively neutral molecule. 19(S)-HETE has been primarily detected in urine. Within the cell, 19(S)-hete is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, 19(S)-hete is involved in the tenoxicam action pathway, the trisalicylate-choline action pathway, the ketoprofen action pathway, and the ketorolac action pathway. 19(S)-HETE is also involved in a couple of metabolic disorders, which include the tiaprofenic Acid action pathway and leukotriene C4 synthesis deficiency. 19(S)-HETE is an intermediate in Arachidonic acid metabolism. 19(S)-HETE is converted from Arachidonic acid via the enzyme CYP2U and Unspecific. Monooxygenase. (EC:1.14.14.1).


12(R)-HPETE is a hydroperoxyeicosatetraenoic acid eicosanoid derived from arachidonic acid. The epidermal lipoxygenases 12R-LOX and eLOX3 act in sequence to convert arachidonic acid via 12(R)-HPETE to 12(R)-HETE and the corresponding epoxyalcohol, 8(R)-hydroxy-11(R),12(R)-epoxyeicosatrienoic acid. The epidermal lipoxygenases 12R-LOX and eLOX3 are the gene products of ALOX12B and ALOXE3. Mutations in ALOXE3 or ALOX12B have been found in families with autosomal-recessive congenital ichthyosis (ARCI). ARCI is a clinically and genetically heterogeneous group of severe hereditary keratinization disorders characterized by intense scaling of the whole integument, and differences in color and shape, often associated with erythema. Mutations in ALOXE3 and ALOX12B on chromosome 17p13, which code for two different epidermal lipoxygenases, were found in patients with ichthyosiform erythroderma. Genetic studies indicated that 12R-lipoxygenase (12R-LOX) or epidermal lipoxygenase-3 (eLOX3) was mutated in six families affected by non-bullous congenital ichthyosiform erythroderma (NCIE), one of the main clinical forms of ichthyosis. (PMID: 16116617, 15629692).


8(S)-HETE is a naturally occurring hydroxyeicosatetraenoic acid eicosanoid. 8(S)-HETE is a strong activator of peroxisome proliferator-activated receptors (PPARs) alpha and a weak activator of PPAR gamma. PPARs are nuclear hormone receptors that regulate gene transcription in response to peroxisome proliferators and fatty acids. PPARs also play an important role in the regulation of adipocyte differentiation. It is unclear however what naturally occurring compounds activate each of the PPAR subtypes. Additionally, 8(S)-HETE is able to induce differentiation of preadipocytes. (PMID: 7592593, 9113987).


8-isoprostane concentrations are elevated in asthma and increase with the clinical severity and during acute asthma episodes. Isoprostane is formed in the airways of asthmatic patients from peroxidation of poly-unsaturated fatty acids in cell membranes, the effect of reactive oxygen species resulting of the NADPH oxidase of eosinophils, neutrophils and alveolar macrophages, which produces superoxide anion which undergoes dismutation to H2O2. (PMID 16354413). 8-isoprostane is also elevated in Bronchopulmonary dysplasia, which remains an important cause of morbidity and mortality in extremely premature newborn infants receiving intensive care and is the most common contributing factor to severe respiratory morbidity and mortality in early childhood. (PMID 14980283). 8-Isoprostaglandin F(2a) is a marker of oxidative stress in the aqueous humour of patients with exfoliation syndrome (XFS) (PubMed ID 12598453).


20-Hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid. Cytochrome P450 enzymes of the 4A and 4F families catalyze the omega-hydroxylation of arachidonic acid and produce 20-HETE. 20-HETE is a potent constrictor of renal, cerebral, and mesenteric arteries. The vasoconstrictor response to 20-HETE is associated with activation of protein kinase, Rho kinase, and the mitogen-activated protein (MAP) kinase pathway C. 20-HETE also increases intracellular Ca2+ by causing the depolarization of vascular smooth muscle membrane secondary to blocking the large-conductance Ca2+-activated K+-channels and by a direct effect on L-type Ca channels. Elevations in the production of 20-HETE mediate the myogenic response of skeletal, renal, and cerebral arteries to elevations in transmural pressure. There is an important interaction between nitric oxide (NO) and the formation of 20-HETE production. NO inhibits the formation of 20-HETE formation in renal and cerebral arteries. A fall in levels of 20-HETE contributes to the cyclic GMP-independent dilator effect of NO to activate the large-conductance Ca2+-activated K+-channels and to dilate the cerebral arteries (PMID: 16258232).


12-HPETE is one of the six monohydroperoxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid (Leukotrienes). Reduction of the hydroperoxide yields the more stable hydroxyl fatty acid (+/-)12-HETE. A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.


12R-Hete, also known as 12-R-hete, belongs to the class of organic compounds known as hydroxyeicosatetraenoic acids. These are eicosanoic acids with an attached hydroxyl group and four CC double bonds. Thus, 12R-hete is considered to be an eicosanoid lipid molecule. 12R-Hete is considered to be a practically insoluble (in water) and relatively neutral molecule.


12-keto-eicosatetraenoic acid is a biologically active eicosanoid in the nervous system of Aplysia.It is a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine.[PMID:2774398].


12S-Hete belongs to the class of organic compounds known as hydroxyeicosatetraenoic acids. These are eicosanoic acids with an attached hydroxyl group and four CC double bonds. Thus, 12S-hete is considered to be an eicosanoid lipid molecule. 12S-Hete is considered to be a practically insoluble (in water) and relatively neutral molecule.


LysoPC(14:0/0:0) is a lysophospholipid (LyP). It is a monoglycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. Lysophosphatidylcholines can have different combinations of fatty acids of varying lengths and saturation attached at the C-1 (sn-1) position. Fatty acids containing 16, 18 and 20 carbons are the most common. LysoPC(14:0/0:0), in particular, consists of one chain of myristic acid at the C-1 position. The myristic acid moiety is derived from nutmeg and butter. Lysophosphatidylcholine is found in small amounts in most tissues. It is formed by hydrolysis of phosphatidylcholine by the enzyme phospholipase A2, as part of the de-acylation/re-acylation cycle that controls its overall molecular species composition. It can also be formed inadvertently during extraction of lipids from tissues if the phospholipase is activated by careless handling. In blood plasma significant amounts of lysophosphatidylcholine are formed by a specific enzyme system, lecithin:cholesterol acyltransferase (LCAT), which is secreted from the liver. The enzyme catalyzes the transfer of the fatty acids of position sn-2 of phosphatidylcholine to the free cholesterol in plasma, with formation of cholesterol esters and lysophosphatidylcholine. Lysophospholipids have a role in lipid signaling by acting on lysophospholipid receptors (LPL-R). LPL-R's are members of the G protein-coupled receptor family of integral membrane proteins.


2,3-dinor-8-epi-prostaglandin F1alpha

5-[(1S,2R)-3,5-Dihydroxy-2-[(1E)-3-hydroxyoct-1-en-1-yl]cyclopentyl]pentanoic acid belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid. 5-[(1S,2R)-3,5-Dihydroxy-2-[(1E)-3-hydroxyoct-1-en-1-yl]cyclopentyl]pentanoic acid is considered to be a practically insoluble (in water) and relatively neutral molecule.


Estradiol

Estradiol is the most potent form of mammalian estrogenic steroids. Estradiol is produced in the ovaries. The ovary requires both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to produce sex steroids. LH stimulates the cells surrounding the follicle to produce progesterone and androgens. The androgens diffuse across the basement membrane to the granulosa cell layer, where, under the action of FSH, they are aromatized to estrogens, mainly estradiol. The ovary shows cyclical activity, unlike the testis that is maintained in a more or less constant state of activity. Hormone secretions vary according to the phase of the menstrual cycle. In the developing follicle LH receptors (LH-R) are only located on the thecal cells and FSH receptors (FSHR) on the granulosa cells. The dominant pre-ovulatory follicle develops LH-Rs on the granulosa cells prior to the LH surge. Thecal cells of the preovulatory follicle also develop the capacity to synthesize estradiol and this persists when the thecal cells become incorporated into the corpus luteum. After ovulation, the empty follicle is remodelled and plays an important role in the second half or luteal phase of the menstrual cycle. This phase is dominated by progesterone and, to a lesser extent, estradiol secretion by the corpus luteum. estradiol is also synthesized locally from cholesterol through testosterone in the hippocampus and acts rapidly to modulate neuronal synaptic plasticity. Localization of estrogen receptor alpha (ERalpha) in spines in addition to nuclei of principal neurons implies that synaptic ERalpha is responsible for rapid modulation of synaptic plasticity by endogenous estradiol. estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and hepatic stellate cells activation by inhibiting a generation of reactive oxygen species in primary cultures. This suggests that the greater progression of hepatic fibrosis and hepatocellular carcinoma in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. estradiol has been reported to induce the production of interferon (INF)-gamma in lymphocytes, and augments an antigen-specific primary antibody response in human peripheral blood mononuclear cells. IFN-gamma is a potent cytokine with immunomodulatory and antiproliferative properties. Therefore, female subjects, particularly before menopause, may produce antibodies against hepatitis B virus e antigen and hepatitis B virus surface antigen at a higher frequency than males with chronic hepatitis B virus infection. The estradiol-Dihydrotestosterone model of prostate cancer (PC) proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol. (PMID: 17708600, 17678531, 17644764).


Testosterone

19-Oxotestosterone is catalyzed by Aromatase (EC 1.14.14.1),also called estrogen synthetase (a cytochrome P450 enzyme which catalyzes the formation of aromatic C18 estrogens from C19 androgens; it is symbolized CYP19) into oestrogens via sequential oxidations at the 19-methyl group. Biosynthesis of estrogens from C19 steroids is catalyzed by aromatase and its tissue-specific expression is determined at least in part by alternative use of tissue-specific promoters, which give rise to transcripts with unique 5-prime noncoding termini.(OMIM 107910).


19-Hydroxyandrost-4-ene-3,17-dione, also known as 19-haed, belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans. Thus, 19-hydroxyandrost-4-ene-3,17-dione is considered to be a steroid lipid molecule. 19-Hydroxyandrost-4-ene-3,17-dione is considered to be a practically insoluble (in water) and relatively neutral molecule. 19-Hydroxyandrost-4-ene-3,17-dione has been found in human testicle, placenta and hepatic tissues, and has also been detected in multiple biofluids, such as blood and urine. Within the cell, 19-hydroxyandrost-4-ene-3,17-dione is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, 19-hydroxyandrost-4-ene-3,17-dione is involved in the androgen and estrogen metabolism pathway and the androstenedione metabolism pathway. 19-Hydroxyandrost-4-ene-3,17-dione is also involved in a couple of metabolic disorders, which include aromatase deficiency and 17-Beta hydroxysteroid dehydrogenase III deficiency. Outside of the human body, 19-hydroxyandrost-4-ene-3,17-dione can be found in a number of food items such as caraway, mentha (mint), jicama, and hard wheat. This makes 19-hydroxyandrost-4-ene-3,17-dione a potential biomarker for the consumption of these food products. 19-Hydroxyandrost-4-ene-3,17-dione is a substrate for Corticotropin-lipotropin and Cytochrome P450 19A1.


19-Hydroxytestosterone is an intermediate in Androgen and estrogen metabolism. 19-Hydroxytestosterone is the 4th to last step in the synthesis of 16-Glucuronide-estriol. It is generated from Testosterone via the enzyme cytochrome P450 (EC 1.14.14.1) and then converted to 19-Oxotestosterone.


17beta-estradiol 3-glucosiduronic acid

Estradiol gulcuronide is believed to play important roles in the mechanism of 17beta-estradiol(E2)-mediated tumor formation. Conjugation with glucuronic acid lowers tissue levels by facilitating excretion.The heterotropic activation by daidzein appears to be specific for the glucuronidation of E2 because daidzein did not affect the glucuronidation of the 2- and 4-hydroxy metabolites of E2. (PMID: 16598814).


Androstenedione

Androstenedione is a delta-4 19-carbon steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol. It is the common precursor of male and female sex hormones. Some androstenedione is also secreted into the plasma, and may be converted in peripheral tissues to testosterone and estrogens. Androstenedione originates either from the conversion of dehydroepiandrosterone or from 17-hydroxyprogesterone. It is further converted to either testosterone or estrone. The production of adrenal androstenedione is governed by ACTH, while production of gonadal androstenedione is under control by gonadotropins.


Hydroxyprogesterone

It serves as an intermediate in the biosynthesis of hydrocortisone and gonadal steroid hormones. It is derived from progesterone via 17-hydroxylase, a P450c17 enzyme, or from 17-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase. 17-Hydroxyprogesterone is a natural progestin and in pregnancy increases in the third trimester primarily due to fetal adrenal production. This hormone is primarily produced in the adrenal glands and to some degree in the gonads, specifically the corpus luteum of the ovary. Normal levels are 3-90 ng/dl in children, and in women, 15-70 ng/dl prior to ovulation, and 35-290 ng/dl during the luteal phase. Measurements of levels of 17-hydroxyprogesterone are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17OHP. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17OHP. 17OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but not 17OHP is also contributed by the placenta.


17a-Hydroxypregnenolone is a 21-carbon steroid that is converted from pregnenolone by cytochrome P450 17alpha hydroxylase/C17,20 lyase (CYP17, EC 1.14.99.9). 17a-Hydroxypregnenolone is an intermediate in the delta-5 pathway of biosynthesis of gonadal steroid hormones and the adrenal corticosteroids. The first, rate-limiting and hormonally regulated step in the biosynthesis of all steroid hormones is the conversion of cholesterol to pregnenolone. The conversion of cholesterol to pregnenolone is accomplished by the cleavage of the cholesterol side chain, catalyzed by a mitochondrial cytochrome P450 enzyme termed P450scc where scc designates Side Chain Cleavage. All steroid hormones are made from the pregnenolone produced by P450scc; thus, the presence or absence of each of the activities of CYP17 directs this pregnenolone towards its final metabolic pathway. While all cytochrome P450 enzymes can catalyze multiple reactions on a single active site, CYP17 is the only one described to date in which these multiple activities are differentially regulated by a physiologic process. 17a-Hydroxypregnenolone is converted to dehydroepiandrosterone by the 17,20 lyase activity of CYP17. The ratio of the 17,20 lyase to 17 alpha-hydroxylase activity of CYP17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated post-translationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase, the presence of cytochrome b5, and the serine phosphorylation of CYP17. (PMID: 12573809).


Prasterone

Dehydroepiandrosterone (DHEA) is a natural steroid hormone produced from cholesterol by the adrenal glands. DHEA is also produced in the gonads, adipose tissue, and the brain. DHEA is structurally similar to and is a precursor of, androstenedione, testosterone, estradiol, estrone, and estrogen. It is the most abundant hormone in the human body. Most of DHEA is sulfated (dehydroepiandrosterone sulfate or DHEA-S) before secretion. DHEA-S is the sulfated version of DHEA; this conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestines. In blood, most DHEA is found as DHEA-S with levels that are about 300 times higher than free DHEA. Blood measurements of DHEA-S/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have normal or mildly elevated levels of DHEA-S.


Prasterone sulfate

Dehydroepiandrosterone sulfate or DHEA-S is the sulfated form of dehydroepiandrosterone (DHEA). This sulfation is reversibly catalyzed by sulfotransferase 2A1 (SULT2A1) primarily in the adrenals, the liver, and small intestine. In the blood, most DHEA is found as DHEA-S with levels that are about 300 times higher than those of free DHEA. Orally-ingested DHEA is converted into its sulfate when passing through the intestines and liver. Whereas DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation. From a practical point of view, measurement of DHEA-S is preferable to DHEA since levels are more stable. DHEA (from which DHEA-S comes from) is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain, and in the skin (by an autocrine mechanism). DHEA is the precursor of androstenedione, which can undergo further conversion to produce the androgen testosterone and the estrogens estrone and estradiol. DHEA is also a potent sigma-1 agonist. Serum dehydroepiandrosterone sulfate is a classic marker for adrenarche, and subsequently for the individual hormonal milieu (PMID: 10599744). Dehydroepiandrosterone sulfate is an endogenously produced sex steroid that has been hypothesized to have anti-aging effects (PMID: 16960027). It also has been inversely associated with the development of atherosclerosis (PMID: 8956025).


Stanolone

Dihydrotestosterone is a potent androgenic metabolite of testosterone. Dihydrotestosterone (DHT) is generated by a 5-alpha reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol therefore DHT is considered a pure androgenic steroid. -- Pubchem; Dihydrotestosterone (DHT) (INN: androstanolone) is a biologically active metabolite of the hormone testosterone, formed primarily in the prostate gland, testes, hair follicles, and adrenal glands by the enzyme 5-alpha-reductase by means of reducing the alpha 4,5 double-bond. Dihydrotestosterone belongs to the class of compounds called androgens, also commonly called androgenic hormones or testoids. DHT is thought to be approximately 30 times more potent than testosterone because of increased affinity to the androgen receptor. -- Wikipedia.


testosterone 17-glucosiduronic acid

Testosterone glucuronide is a natural human metabolite of testosterone. Testosterone is a steroid hormone from the androgen group. Testosterone is primarily secreted in the testes of males and the ovaries of females although small amounts are secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid. In both males and females, it plays key roles in health and well-being. There is a sex difference in the median values of testosterone glucuronide in the amniotic fluid specimens 15-19 wk gestation between female (median 160 pM, range 64-465 pM) and male (median 817 pM, range 68-3707 pM). This difference, when used in conjunction with amniotic fluid unconjugated testosterone values, increase the predictive accuracy of fetal sexing from 95.4 to 98.9%. In human newborns and young infants, urinary testosterone sulfate is higher than glucuronide. The high sulfokinase activity in fetal and neonatal testes is more likely responsible for this phenomenon than an impaired glucuronizing capacity of the liver. Urinary excretion of testosterone glucuronide increases significantly during puberty. The level of testosterone glucuronide exceeds the level of unconjugated testosterone in human seminal plasma. Urinary testosterone glucuronide excretion is increased in women with virilizing adrenocortical tumors. Concentration of testosterone glucuronide in urine from women with breast tumor in urine samples is not different from patients with benign or malignant breast disease, either before or after the menopause. (PMID: 8327267, 3560942, 6246233, 871373, 133773, 947290).


smooth endoplasmic reticulum lumen

biolink:CellularComponent biolink:AnatomicalEntity biolink:PhysicalEssence biolink:OrganismalEntity biolink:SubjectOfInvestigation biolink:BiologicalEntity biolink:ThingWithTaxon biolink:NamedThing biolink:PhysicalEssenceOrOccurrent


D-glucose

Glucose is a monosaccharide containing six carbon atoms and an aldehyde group and is therefore referred to as an aldohexose. The glucose molecule can exist in an open-chain (acyclic) and ring (cyclic) form, the latter being the result of an intramolecular reaction between the aldehyde C atom and the C-5 hydroxyl group to form an intramolecular hemiacetal. In water solution both forms are in equilibrium and at pH 7 the cyclic one is the predominant. Glucose is a primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. In animals glucose arises from the breakdown of glycogen in a process known as glycogenolysis. Glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate and glycerol, by a process known as gluconeogenesis.

Roferose st
(+)-glucose
Anhydrous dextrose
Cpc hydrate
Cerelose
Cerelose 2001
Clearsweet 95
Clintose l
Corn sugar
D(+)-glucose
Dextropur
Dextrose
Dextrosol
Glucodin
Glucolin
Glucose
Goldsugar
Grape sugar
Meritose
Staleydex 111
Staleydex 95m
Tabfine 097(hs)
Vadex
D-glc
D-glcp
D-glucose


vitamin K epoxide

Vitamin K1 2,3-epoxide is a vitamin K derivative. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation. Within the cell, vitamin K undergoes electron reduction to a reduced form of vitamin K (called vitamin K hydroquinone) by the enzyme vitamin K epoxide reductase (or VKOR). Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of glutamate into gamma-carboxyglutamate (Gla). This enzyme is called the gamma-glutamyl carboxylase or the vitamin K-dependent carboxylase. The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone into vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions. Vitamin K epoxide is then re-converted into vitamin K by the vitamin K epoxide reductase. These two enzymes comprise the so-called vitamin K cycle. One of the reasons why vitamin K is rarely deficient in a human diet is because vitamin K is continually recycled in our cells. Vitamin K 2,3-epoxide is the substrate for vitamin K 2,3-epoxide reductase (VKOR) complex. Significantly increased level of serum vitamin K epoxide has been found in patients with familial multiple coagulation factor deficiency (PMID: 12384421). Accumulation of vitamin K1-2,3-epoxide in plasma is also a sensitive marker of coumarin-like activity of drugs (PMID: 2401753).


Phylloquinol

Phylloquinol, also known as phytonadiol or dihydrovitamin K1, belongs to the class of organic compounds known as diterpenoids. These are terpene compounds formed by four isoprene units. Thus, phylloquinol is considered to be a quinone lipid molecule. Phylloquinol is considered to be a practically insoluble (in water) and relatively neutral molecule. Within the cell, phylloquinol is primarily located in the membrane (predicted from logP) and cytoplasm. Outside of the human body, phylloquinol can be found in a number of food items such as amaranth, strawberry, summer grape, and prunus (cherry, plum). This makes phylloquinol a potential biomarker for the consumption of these food products. Phylloquinol is the final product of phylloquinol biosynthesis.


DITHIOTHREITOL

Dithiothreitol (DTT) is the common name for a small-molecule redox reagent known as Cleland's reagent. DTT's formula is C4H10O2S2 and the molecular structure of its reduced form is shown at the right; its oxidized form is a disulfide-bonded 6-membered ring (shown below). Its name derives from the four-carbon sugar, threose. DTT has an epimeric ('sister') compound, dithioerythritol. A common use of DTT is as a reducing or "deprotecting" agent for thiolated DNA. The terminal sulfur atoms of thiolated DNA have a tendency to form dimers in solution, especially in the presence of oxygen. Dimerization greatly lowers the efficiency of subsequent coupling reactions such as DNA immobilization on gold in biosensors. Typically DTT is mixed with a DNA solution and allowed to react, and then is removed by filtration (for the solid catalyst) or by chromatography (for the liquid form). The DTT removal procedure is often called "desalting.". DTT is frequently used to reduce the disulfide bonds of proteins and, more generally, to prevent intramolecular and intermolecular disulfide bonds from forming between cysteine residues of proteins. However, even DTT cannot reduce buried (solvent-inaccessible) disulfide bonds, so reduction of disulfide bonds is sometimes carried out under denaturing conditions (e.g., at high temperatures, or in the presence of a strong denaturant such as 6 M guanidinium hydrochloride, 8 M urea, or 1% sodium dodecylsulfate). Conversely, the solvent exposure of different disulfide bonds can be assayed by their rate of reduction in the presence of DTT. DTT can also be used as an oxidizing agent. Its principal advantage is that effectively no mixed-disulfide species are populated, in contrast to other agents such as glutathione. In very rare cases, a DTT adduct may be formed, i.e., the two sulfur atoms of DTT may form disulfide bonds to different sulfur atoms; in such cases, DTT cannot cyclize since it has no remaining free thiols. Due to air oxidation, DTT is a relatively unstable compound whose useful life can be extended by refrigeration and handling in an inert atmosphere. Since protonated sulfurs have lowered nucleophilicities, DTT becomes less potent as the pH lowers. Tris(2-carboxyethyl)phosphine HCl (TCEP hydrochloride) is an alternative which is more stable and works even at low pH.


Oxidized dithiothreitol, also known as dithiane diol, belongs to the class of organic compounds known as dithianes. Dithianes are compounds containing a dithiane moiety, which is composed of a cyclohexane core structure wherein two methylene units are replaced by sulfur centres. Oxidized dithiothreitol is soluble (in water) and a very weakly acidic compound (based on its pKa). In humans, oxidized dithiothreitol is involved in the vitamin K metabolism pathway. Oxidized dithiothreitol is part of the Ubiquinone and other terpenoid-quinone biosynthesis pathway. It is a substrate for: Vitamin K epoxide reductase complex subunit 1.


1-palmitoyl-sn-glycerol 3-phosphate

LPA(16:0/0:0) is a lysophosphatidic acid. It is a glycerophospholipid in which a phosphate moiety occupies a glycerol substitution site. Lysophosphatidic acids can have different combinations of fatty acids of varying lengths and saturation attached at the C-1 (sn-1) or C-2 (sn-2) position. Fatty acids containing 16 and 18 carbons are the most common.LPA(16:0/0:0), in particular, consists of one hexadecanoyl chain.  Lysophosphatidic acid is the simplest possible glycerophospholipid. It is the biosynthetic precursor of phosphatidic acid. Although it is present at very low levels only in animal tissues, it is extremely important biologically, influencing many biochemical processes.

2-hydroxy-3-(phosphonooxy)propyl ester hexadecanoic acid


PA(16:0/16:0)is a phosphatidic acid. It is a glycerophospholipid in which a phosphate moiety occupies a glycerol substitution site. As is the case with diacylglycerols, phosphatidic acids can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 16, 18 and 20 carbons are the most common. PA(16:0/16:0), in particular, consists of two hexadecanoyl chain at positions C-1 and C2. The oleic acid moiety is derived from vegetable oils, especially olive and canola oil, while the oleic acid moiety is derived from vegetable oils, especially olive and canola oil. Phosphatidic acids are quite rare but are extremely important as intermediates in the biosynthesis of triacylglycerols and phospholipids.


CDP-diacylglycerol

CDP-DG(16:0/16:0) belongs to the family of CDP-diacylglycerols. It is a glycerophospholipid containing a diacylglycerol, with a cytidine diphosphate attached to the oxygen O1 or O2 of the glycerol part. As is the case with diacylglycerols, phosphatidylserines can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. CDP-DG(16:0/16:0), in particular, consists of two hexadecanoyl chain at positions C-1 and C2. In E. coli glycerophospholipid metabolism, The biosynthesis of CDP-diacylglycerol (CDP-DG) involves condensation of phosphatidic acid (PA) and cytidine triphosphate, with elimination of pyrophosphate, catalysed by the enzyme CDP-diacylglycerol synthase. The resulting CDP-diacylglycerol can be utilized immediately for the synthesis of phosphatidylglycerol (PG), and thence cardiolipin (CL), and of phosphatidylinositol (PI). CDP-DG(16:0/16:0)  is also a substrate of CDP-diacylglycerol pyrophosphatase. It is involved in CDP-diacylglycerol degradation pathway.


Acetylcholine

Acetylcholine (ACh) is a neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Its physiological and pharmacological effects, metabolism, release, and receptors have been well documented in several species. ACh has been considered an important excitatory neurotransmitter in the carotid body (CB). Various nicotinic and muscarinic ACh receptors are present in both afferent nerve endings and glomus cells. Therefore, ACh can depolarize or hyperpolarize the cell membrane depending on the available receptor type in the vicinity. Binding of ACh to its receptor can create a wide variety of cellular responses including opening cation channels (nicotinic ACh receptor activation), releasing Ca2+ from intracellular storage sites (via muscarinic ACh receptors), and modulating activities of K+ and Ca2+ channels. Interactions between ACh and other neurotransmitters (dopamine, adenosine, nitric oxide) have been known, and they may induce complicated responses. Cholinergic biology in the CB differs among species and even within the same species due to different genetic composition. Development and environment influence cholinergic biology. Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors have a role in the encoding of new memories. Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine has been shown to increase the strength of afferent input relative to feedback, to contribute to theta rhythm oscillations, activate intrinsic mechanisms for persistent spiking, and increase the modification of synapses. These effects might enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories. The role of ACh in attention has been repeatedly demonstrated in several tasks. Acetylcholine is linked to response accuracy in voluntary and reflexive attention and also to response speed in reflexive attention. It is well known that those with Attention-deficit/hyperactivity disorders tend to be inaccurate and slow to respond. (PMID: 17284361, 17011181, 15556286).

Ach
Acetyl choline ion
Acetylcholine cation
Acetylcholinium: acetyl-choline
Choline acetate
Choline acetate (ester)
O-acetylcholine


Citicoline

Citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product (PMID: 17171187).

Cytidine 5'-(cholinyl pyrophosphoric acid)


LysoPC(16:0) is a lysophospholipid (LyP). It is a monoglycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. Lysophosphatidylcholines can have different combinations of fatty acids of varying lengths and saturation attached at the C-1 (sn-1) position. Fatty acids containing 16, 18 and 20 carbons are the most common. LysoPC(16:0), in particular, consists of one chain of palmitic acid at the C-1 position. The palmitic acid moiety is derived from fish oils, milk fats, vegetable oils and animal fats. Lysophosphatidylcholine is found in small amounts in most tissues. It is formed by hydrolysis of phosphatidylcholine by the enzyme phospholipase A2, as part of the de-acylation/re-acylation cycle that controls its overall molecular species composition. It can also be formed inadvertently during extraction of lipids from tissues if the phospholipase is activated by careless handling. In blood plasma significant amounts of lysophosphatidylcholine are formed by a specific enzyme system, lecithin:cholesterol acyltransferase (LCAT), which is secreted from the liver. The enzyme catalyzes the transfer of the fatty acids of position sn-2 of phosphatidylcholine to the free cholesterol in plasma, with formation of cholesterol esters and lysophosphatidylcholine. Lysophospholipids have a role in lipid signaling by acting on lysophospholipid receptors (LPL-R). LPL-R's are members of the G protein-coupled receptor family of integral membrane proteins.

(2r)-2-hydroxy-3-(hexadecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphoric acid


PC(16:0/16:0) is a phosphatidylchloline (PC). It is a glycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. As is the case with diacylglycerols, phosphatidylcholines can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. PC(16:0/16:0), in particular, consists of two hexadecanoyl chains at positions C-1 and C-2. In E. coli, PCs can be found in the integral component of the cell outer membrane. They are hydrolyzed by Phospholipases to a 2-acylglycerophosphocholine and a carboxylate.

(r)-4-hydroxy-n,n,n-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-3,5,9-trioxa-4-phosphapentacosan-1-aminium 4-oxide hydroxide inner salt


phosphocholine

Phosphorylcholine is a small haptenic molecule, is found in a wide variety of organisms. Human hepatic tumors undergo an elevation in the concentration of phosphorylcholine as the principal metabolic change is observed (PMID: 11076016). Phosphorylcholine is the precursor metabolite of choline in the glycine, serine and threonine metabolism pathways (KEGG, map00260) and in intermediate between choline and cytidine-diphosphate choline in the glycerophospholipid metabolism pathway (KEGG, map00564).


PE(16:0/16:0) is a phosphatidylethanolamine. It is a glycerophospholipid in which a phosphorylethanolamine moiety occupies a glycerol substitution site. As is the case with diacylglycerols, glycerophosphoethanolamines can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. PE(16:0/16:0), in particular, consists of two hexadecanoyl chains at positions C-1 and C-2. While most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone, the fatty acid distribution at the C-1 and C-2 positions of glycerol within phospholipids is continually in flux, owing to phospholipid degradation and the continuous phospholipid remodeling that occurs while these molecules are in membranes. PEs are neutral zwitterions at physiological pH. They mostly have palmitic or stearic acid on carbon 1 and a long chain unsaturated fatty acid (e.g. 18:2, 20:4 and 22:6) on carbon 2. PE synthesis can occur via two pathways. The first requires that ethanolamine be activated by phosphorylation and then coupled to CDP. The ethanolamine is then transferred from CDP-ethanolamine to phosphatidic acid to yield PE. The second involves the decarboxylation of PS.


LysoPE(16:0/0:0) is a lysophosphatidylethanolamine or a lysophospholipid. The term 'lysophospholipid' (LPL) refers to any phospholipid that is missing one of its two O-acyl chains. Thus, LPLs have a free alcohol in either the sn-1 or sn-2 position. The prefix 'lyso-' comes from the fact that lysophospholipids were originally found to be hemolytic however it is now used to refer generally to phospholipids missing an acyl chain. LPLs are usually the result of phospholipase A-type enzymatic activity on regular phospholipids such as phosphatidylcholine or phosphatidic acid, although they can also be generated by the acylation of glycerophospholipids or the phosphorylation of monoacylglycerols. Some LPLs serve important signaling functions such as lysophosphatidic acid. Lysophosphatidylethanolamines (LPEs) can function as plant growth regulators with several diverse uses. (LPEs) are approved for outdoor agricultural use to accelerate ripening and improve the quality of fresh produce. They are also approved for indoor use to preserve stored crops and commercial cut flowers. As a breakdown product of phosphatidylethanolamine (PE), LPE is present in cells of all organisms.

2-ammonioethyl (2r)-2-hydroxy-3-(palmitoyloxy)propyl phosphoric acid


L-alpha-Glycerophosphorylethanolamine

Glycerylphosphorylethanolamine, also known as gpea, belongs to the class of organic compounds known as organic phosphoramides. These are organic compounds containing the phosphoric acid amide functional group. Glycerylphosphorylethanolamine is soluble (in water) and a moderately acidic compound (based on its pKa). Glycerylphosphorylethanolamine has been found in human brain, prostate and liver tissues. Within the cell, glycerylphosphorylethanolamine is primarily located in the cytoplasm. Glycerylphosphorylethanolamine exists in all living organisms, ranging from bacteria to humans. In humans, glycerylphosphorylethanolamine is involved in phospholipid biosynthesis pathway. Glycerylphosphorylethanolamine is a membrane breakdown product resulting from the cleavage of the lipid group from glycerophosphoethanlomine fatty acids (i.e. phosphatidylethanolamine). It acts as a growth stimulant for hepatocytes.

2-aminoethyl ester 1-glycerophosphoric acid


Ethanolamine

Ethanolamine is a viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorometric reagent, and to remove CO2 and H2S from natural gas and other gases.

1-amino-2-hydroxyethane
2-amino-1-ethanol
2-aminoethanol
2-aminoethyl alcohol
2-ethanolamine
2-hydroxyethanamine
2-hydroxyethylamine
Aethanolamin
Aminoethanol
Colamine
Envision conditioner pdd 9020
Ethanolamine
Ethylolamine
Glycinol
H-glycinol
Mea
Monoaethanolamin
Monoethanolamine
Olamine
B-aminoethanol
B-aminoethyl alcohol
B-ethanolamine
B-hydroxyethylamine
Beta-aminoethanol
Beta-aminoethyl alcohol
Beta-ethanolamine
Beta-hydroxyethylamine
Eta
2-amino-ethanol
2-aminoethan-1-ol
Hea
β-aminoethanol
β-aminoethyl alcohol
β-ethanolamine
β-hydroxyethylamine


PS(16:0/16:0) is a phosphatidylserine. It is a glycerophospholipid in which a phosphorylserine moiety occupies a glycerol substitution site. As is the case with diacylglycerols, phosphatidylserines can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. PS(16:0/16:0), in particular, consists of two hexadecanoyl chains at positions C-1 and C-2. Phosphatidylserine or 1,2-diacyl-sn-glycero-3-phospho-L-serine is distributed widely among animals, plants and microorganisms. Phosphatidylserine is an acidic (anionic) phospholipid with three ionizable groups, i.e. the phosphate moiety, the amino group and the carboxyl function. As with other acidic lipids, it exists in nature in salt form, but it has a high propensity to chelate to calcium via the charged oxygen atoms of both the carboxyl and phosphate moieties, modifying the conformation of the polar head group. This interaction may be of considerable relevance to the biological function of phosphatidylserine. While most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone, the fatty acid distribution at the C-1 and C-2 positions of glycerol within phospholipids is continually in flux, owing to phospholipid degradation and the continuous phospholipid remodeling that occurs while these molecules are in membranes. Phosphatidylserines typically carry a net charge of -1 at physiological pH. They mostly have palmitic or stearic acid on carbon 1 and a long chain unsaturated fatty acid (e.g. 18:2, 20:4 and 22:6) on carbon 2. PS biosynthesis involves an exchange reaction of serine for ethanolamine in PE.


PGP(16:0/16:0) belongs to the class of glycerophosphoglycerophosphates, also called phosphatidylglycerophosphates (PGPs). These lipids contain a common glycerophosphate skeleton linked to at least one fatty acyl chain and a glycero-3-phosphate moiety. As is the case with diacylglycerols, phosphatidylglycerophosphates can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. PGP(16:0/16:0), in particular, consists of two hexadecanoyl chains at positions C-1 and C-2. In E. coli, PGPs can be found in the cytoplasmic membrane. The are synthesized by the addition of glycerol 3-phosphate to a CDP-diacylglycerol. In turn, PGPs are dephosphorylated to Phosphatidylglycerols (PGs) by the enzyme Phosphatidylglycerophosphatase.


PG(16:0/16:0) is a phosphatidylglycerol. Phosphatidylglycerols consist of a glycerol 3-phosphate backbone esterified to either saturated or unsaturated fatty acids on carbons 1 and 2. As is the case with diacylglycerols, phosphatidylglycerols can have many different combinations of fatty acids of varying lengths and saturation attached to the C-1 and C-2 positions. PG(16:0/16:0), in particular, consists of two hexadecanoyl chains at positions C-1 and C-2. In E. coli glycerophospholipid metabolism, phosphatidylglycerol is formed from phosphatidic acid (1,2-diacyl-sn-glycerol 3-phosphate) by a sequence of enzymatic reactions that proceeds via two intermediates, cytidine diphosphate diacylglycerol (CDP-diacylglycerol) and phosphatidylglycerophosphate (PGP, a phosphorylated phosphatidylglycerol). Phosphatidylglycerols, along with CDP-diacylglycerol, also serve as precursor molecules for the synthesis of cardiolipin, a phospholipid found in membranes.


cardiolipin

CL(16:0/16:0/16:0/16:0) is a cardiolipin (CL). Cardiolipins are sometimes called a 'double' phospholipid because they have four fatty acid tails, instead of the usual two. CL(16:0/16:0/16:0/16:0) contains four chains of hexadecanoic acid at the C1, C2, C3 and C4 positions. While the theoretical charge of cardiolipins is -2, under normal physiological conditions (pH near 7), the molecule may carry only one negative charge. In prokaryotes such as E. coli, the enzyme known as diphosphatidylglycerol synthase catalyses the transfer of the phosphatidyl moiety of one phosphatidylglycerol to the free 3'-hydroxyl group of another, with the elimination of one molecule of glycerol. In E. coli, which acylates its glycerophospholipids with acyl chains ranging in length from 12 to 18 carbons and possibly containing an unsaturation, or a cyclopropane group more than 100 possible CL molecular species are theoretically possible, 53 of these species having been characterized. E. coli membranes consist of ~5% cardiolipin (CL), 20-25% phosphatidylglycerol (PG), and 70-80% phosphatidylethanolamine (PE) as well as smaller amounts of phosphatidylserine (PS). CL is distributed between the two leaflets of the bilayers and is located preferentially at the poles and septa in E. coli and other rod-shaped bacteria. It is known that the polar positioning of the proline transporter ProP and the mechanosensitive ion channel MscS in E. coli is dependent on CL. It is believed that cell shape may influence the localization of CL and the localization of certain membrane proteins.


5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position. Uridine 5'-monophosphate is a nucleotide that is found in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase uracil. (Wikipedia).

5'-ump
Ump
Uridine 5'-monophosphate
Uridine 5'-phosphate
Uridine 5'-phosphorate
Uridine 5'-phosphoric acid
Uridine mono(dihydrogen phosphate)
Uridine monophosphate
Uridine phosphate
Uridine-5'-monophosphate
Uridylic acid
5'uridylic acid
Pu
Uridine 5'-(dihydrogen phosphate)
Uridylate


lactose

alpha-Lactose is the major sugar present in milk and the main source of energy supplied to the newborn mammalian in its mother's milk. Lactose is also an important osmotic regulator of lactation. It is digested by the intestinal lactase (EC 3.2.1.108), an enzyme expressed in newborns. Its activity declines following weaning. As a result, adult mammals are normally lactose-intolerant and more than 75% of the human adult population suffers from lactase deficiency. Lactase deficiency is present in up to 80 percent of blacks and Latinos, and up to 100 percent of American Indians and Asians. Persons with lactose intolerance are unable to digest significant amounts of lactose. Common symptoms include abdominal pain and bloating, excessive flatus, and watery stool following the ingestion of foods containing lactose. A sizable number of adults believe they are lactose intolerant but do not actually have impaired lactose digestion, and some persons with lactase deficiency can tolerate moderate amounts of ingested lactose. A diagnosis of lactose intolerance can usually be made with a careful history supported by dietary manipulation. If necessary, diagnosis can be confirmed by using a breath hydrogen or lactose tolerance test. These mostly uncomfortable symptoms of lactose maldigestion are blamed for a variably dairy consumption. There is, however, emerging evidence that certain lactic acid-producing bacteria, which selectively consume prebiotics, may be beneficial against some lower intestinal diseases. Lactose maldigestion and lactose should perhaps be re-evaluated as a potential provider of such a prebiotic. Treatment consists primarily of avoiding lactose-containing foods. Lactase enzyme supplements may be helpful. The degree of lactose malabsorption varies greatly among patients with lactose intolerance, but most of them can ingest up to 350 mL of milk daily without symptoms. Lactose-intolerant patients must ensure adequate calcium intake. (PMID: 13130292, 12216958, 12197838, 12018807).


mevalonic acid

Mevalonic acid is a key organic compound in biochemistry. It is a precursor in the biosynthetic pathway, known as the HMG-CoA reductase pathway, that produces terpenes and steroids. Mevalonate is produced by NADPH from 3-hydroxy-3-methylglutaryl CoA via reduction. This reaction occurs in the cytosol. It is the committed step in cholesterol synthesis, -- Wikipedia The production of mevalonic acid (MVA) by the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, is the rate-limiting step in the biosynthesis of cholesterol. (Jemal et. al, Rapid Communications in Mass Spectrometry, 2003, 17:1715) Plasma concentrations and urinary excretion of MVA are decreased by HMG-CoA reductase inhibitor drugs such as pravastatin, simvastatin and atorvastatin. Naoumova RP, Marais AD, Mountney J, Firth JC, Rendell NB, Taylor GW, Thompson GR. Atherosclerosis 1996; 119: 203.

(3rs)-mevalonate
(3rs)-mevalonic acid
2,4-dideoxy-3-c-methylpentonate
2,4-dideoxy-3-c-methylpentonic acid
3,5-dihydroxy-3-methyl-valerate
3,5-dihydroxy-3-methyl-valeric acid
3,5-dihydroxy-3-methylpentanoate
3,5-dihydroxy-3-methylpentanoic acid
3,5-dihydroxy-3-methylvalerate
3,5-dihydroxy-3-methylvaleric acid
Dl-mevalonate
Dl-mevalonic acid
Hiochic acid
Mk 91
Mva
Mvs
Mevalonate
Mevalonic acid
Rs-mevalonate
Rs-mevalonic acid
B,d-dihydroxy-b-methylvalerate
B,d-dihydroxy-b-methylvaleric acid
B,d-dihydroxy-beta-methylvalerate
B,d-dihydroxy-beta-methylvaleric acid


(R)-5-phosphomevalonic acid

Mevalonic acid-5P, also known as mevalonate-5P or phosphomevalonate, belongs to the class of organic compounds known as monoalkyl phosphates. These are organic compounds containing a phosphate group that is linked to exactly one alkyl chain. Mevalonic acid-5P is soluble (in water) and a moderately acidic compound (based on its pKa). Mevalonic acid-5P has been found throughout most human tissues. Within the cell, mevalonic acid-5P is primarily located in the peroxisome. In humans, mevalonic acid-5P is involved in the pamidronate action pathway, the fluvastatin action pathway, the simvastatin action pathway, and steroid biosynthesis pathway. Mevalonic acid-5P is also involved in several metabolic disorders, some of which include the smith-lemli-opitz syndrome (slos) pathway, the hypercholesterolemia pathway, the wolman disease pathway, and the child syndrome pathway. Outside of the human body, mevalonic acid-5P can be found in a number of food items such as elderberry, persian lime, purple laver, and apple. This makes mevalonic acid-5P a potential biomarker for the consumption of these food products. 5-Phosphomevalonate is a metabolic intermediate in the mevalonate pathway, catalyzed by the enzyme mevalonate kinase from Mevalonate. (wikipedia).


(R)-5-diphosphomevalonic acid

(S)-5-Diphosphomevalonic acid, also known as mevalonate 5-diphosphate or (S)-mevalonic acid-5-pyrophosphate, belongs to the class of organic compounds known as organic pyrophosphates. These are organic compounds containing the pyrophosphate oxoanion, with the structure OP([O-])(=O)OP(O)([O-])=O (S)-5-Diphosphomevalonic acid is slightly soluble (in water) and a moderately acidic compound (based on its pKa). Within the cell, (S)-5-diphosphomevalonic acid is primarily located in the peroxisome. In humans, (S)-5-diphosphomevalonic acid is involved in the risedronate action pathway, the ibandronate action pathway, steroid biosynthesis pathway, and the lovastatin action pathway (S)-5-Diphosphomevalonic acid is also involved in several metabolic disorders, some of which include the mevalonic aciduria pathway, the cholesteryl ester storage disease pathway, lysosomal acid lipase deficiency (wolman disease), and the hypercholesterolemia pathway. Outside of the human body, (S)-5-diphosphomevalonic acid can be found in a number of food items such as peanut, rowanberry, buffalo currant, and garden rhubarb. This makes (S)-5-diphosphomevalonic acid a potential biomarker for the consumption of these food products. 5-pyrophosphomevalonate is a metabolic intermediate in the mevalonate pathway, catalyzed by the enzyme phosphomevalonate kinase from 5-phosphomevalonate. (wikipedia).


ISOPENTENYL PYROPHOSPHATE

Isopentenyl pyrophosphate, IPP or isopentenyl diphosphate, is an intermediate in the HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from Mevalonate-5-pyrophosphate, in a reaction catalyzed by the enzyme mevalonate-5-pyrophosphate decarboxylase. (wikipedia).

Diphosphoric acid mono(3-methyl-3-butenyl) ester

3-methylbut-3-enyl phosphono hydrogen phosphate

3-methylbut-3-en-1-yl trihydrogen diphosphoric acid

3-methylbut-3-enyl phosphono hydrogen phosphoric acid


Dimethylallyl Diphosphate

Dimethylallylpyrophosphate, also known as 2-isopentenyl diphosphate or delta-prenyl diphosphate, belongs to the class of organic compounds known as isoprenoid phosphates. These are prenol lipids containing a phosphate group linked to an isoprene (2-methylbuta-1,3-diene) unit. Dimethylallylpyrophosphate exists as a solid, slightly soluble (in water), and a moderately acidic compound (based on its pKa). Dimethylallylpyrophosphate has been found in human muscle tissue. Within the cell, dimethylallylpyrophosphate is primarily located in the peroxisome, cytoplasm and mitochondria. Dimethylallylpyrophosphate exists in all living organisms, ranging from bacteria to humans. In humans, dimethylallylpyrophosphate is involved in the lovastatin action pathway, the desmosterolosis pathway, the risedronate action pathway, and the ibandronate action pathway. Dimethylallylpyrophosphate is also involved in several metabolic disorders, some of which include the wolman disease pathway, the chondrodysplasia punctata II, X linked dominant (CDPX2) pathway, the mevalonic aciduria pathway, and the child syndrome pathway. Outside of the human body, dimethylallylpyrophosphate can be found in a number of food items such as ucuhuba, yellow wax bean, white cabbage, and european plum. This makes dimethylallylpyrophosphate a potential biomarker for the consumption of these food products. Dimethylallyl pyrophosphate (or -diphosphate) (DMAPP) is an intermediate product of both mevalonic acid (MVA) pathway and DOXP/MEP pathway. It is an isomer of isopentenyl pyrophosphate (IPP) and exists in virtually all life forms. (wikipedia).

Diphosphoric acid mono(3-methyl-2-butenyl) ester


Geranyl-PP

Geranyl diphosphate is the precursor of monoterpenes, a large family of natural occurring C10 compounds predominately found in plants and animals. Geranyl diphosphate is regarded as a key intermediate in the steroid, isoprene and terpene biosynthesis pathways and is used by organisms in the biosynthesis of farnesyl pyrophosphate, geranylgeranyl pyrophosphate, cholesterol, terpenes and terpenoids. (wikipedia). In humans, geranyl diphosphate synthase (GPPS) catalyzes the condensation of dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) to form geranyl diphosphate. Animals produce IPP through the mevalonate (MVA) pathway. Isoprenoid compounds have been implicated in several human disease states including coronary heart disease, blindness, infectious hepatitis and cancer. Geranyl pyrophosphate is an intermediate in the HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. -- Wikipedia.


Farnesyl diphosphate

Farnesyl pyrophosphate, also known as farnesyl diphosphoric acid or farnesyl-PP, belongs to the class of organic compounds known as sesquiterpenoids. These are terpenes with three consecutive isoprene units. Farnesyl pyrophosphate is considered to be a practically insoluble (in water) and relatively neutral molecule. Farnesyl pyrophosphate has been found in human testicle tissue, and has also been primarily detected in blood. Farnesyl pyrophosphate can be found anywhere throughout the human cell, such as in membrane (predicted from logP), peroxisome, mitochondria, and endoplasmic reticulum. Farnesyl pyrophosphate exists in all living organisms, ranging from bacteria to humans. Farnesyl pyrophosphate participates in a number of enzymatic reactions. In particular, Ferroheme b and farnesyl pyrophosphate can be converted into heme O; which is mediated by the enzyme heme O synthase. Furthermore, Farnesyl pyrophosphate and isopentenyl pyrophosphate can be converted into octaprenyl diphosphate through the action of the enzyme octaprenyl diphosphate synthase. Furthermore, Farnesyl pyrophosphate can be biosynthesized from geranyl-PP and isopentenyl pyrophosphate through its interaction with the enzyme geranyl diphosphate synthase / farnesyl diphosphate synthase. Finally, Farnesyl pyrophosphate and isopentenyl pyrophosphate can be converted into di-trans,octa-cis-undecaprenyl diphosphate; which is catalyzed by the enzyme undecaprenyl diphosphate synthase. In humans, farnesyl pyrophosphate is involved in the simvastatin action pathway, the risedronate action pathway, the alendronate action pathway, and the ibandronate action pathway. Farnesyl pyrophosphate is also involved in several metabolic disorders, some of which include the hyper-igd syndrome pathway, the chondrodysplasia punctata II, X linked dominant (CDPX2) pathway, the porphyria variegata (PV) pathway, and lysosomal acid lipase deficiency (wolman disease). Outside of the human body, farnesyl pyrophosphate can be found in a number of food items such as sweet basil, apple, spearmint, and nuts. This makes farnesyl pyrophosphate a potential biomarker for the consumption of these food products. Farnesyl pyrophosphate is an intermediate in the HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. -- Wikipedia.


Squalene

Squalene is a natural raw material found in human sebum (5%) and in shark-liver oil. An unsaturated aliphatic hydrocarbon (carotenoid) with six unconjugated double bonds. (Hawley's Condensed Chemical Reference) Biological Source: Found in fish liver oils, yeast lipids and many vegetable oils, e.g. palm oil, cottonseed oil, rapeseed oil. Volatile component of scent material from Saguinus oedipus (cotton-top tamarin monkey) and Saguinus fuscicollis (saddle-back tamarin monkey). Component of adult human sebum principally responsible for the fixing of fingerprints (ChemNetBase) Squalene is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though there are botanical sources as well, including rice bran, wheat germ, and olives. All higher organisms produce squalene, including humans. It is a hydrocarbon and a triterpene. -- Wikipedia; Squalene is the biochemical precursor to the whole family of steroids. Oxidation of one of the terminal double bonds of squalene yields 2,3-squalene oxide which undergoes enzyme-catalyzed cyclization to afford lanosterol, which is then elaborated into cholesterol and other steroids. -- Wikipedia; Squalene is a low density compound often stored in the bodies of cartilaginous fishes such as sharks, which lack a swim bladder and must therefore reduce their body density with fats and oils. Squalene, which is stored mainly in the shark's liver, is lighter than water with a specific gravity of 0.855. -- Wikipedia Uses: Bactericide. Intermediate in the manufacture of pharmaceuticals, rubber chemicals and coloring materials (Physical Constants of Chemical Substances).


(S)-2,3-Epoxysqualene, also known as (S)-squalene-2,3-epoxide, belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing six isoprene units (S)-2,3-Epoxysqualene is considered to be a practically insoluble (in water) and relatively neutral molecule. Within the cell, (S)-2,3-epoxysqualene is primarily located in the membrane (predicted from logP), endoplasmic reticulum and cytoplasm. In humans, (S)-2,3-epoxysqualene is involved in the desmosterolosis pathway, the alendronate action pathway, the pamidronate action pathway, and the simvastatin action pathway (S)-2,3-Epoxysqualene is also involved in several metabolic disorders, some of which include the smith-lemli-opitz syndrome (slos) pathway, the chondrodysplasia punctata II, X linked dominant (CDPX2) pathway, the child syndrome pathway, and lysosomal acid lipase deficiency (wolman disease). Outside of the human body, (S)-2,3-epoxysqualene can be found in a number of food items such as roman camomile, loquat, pistachio, and pepper (c. baccatum). This makes (S)-2,3-epoxysqualene a potential biomarker for the consumption of these food products. (S)-2,3-Epoxysqualene is an intermediate in the biosynthesis of Terpenoid. It is a substrate for Squalene monooxygenase and Lanosterol synthase.


Lanosterol

Lanosterol is a tetracyclic triterpenoid which is the compound from which all steroids are derived. Lanosterol is biochemically synthesized starting from acetyl-CoA by the HMG-CoA reductase pathway. The critical step is the enzymatic conversion of the acyclic terpene squalene to the polycylic lanosterol via 2,3-squalene oxide.(wikipedia).


lanostenol

24,25-Dihydrolanosterol, also known as lanostenol, belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing six isoprene units. Thus, 24,25-dihydrolanosterol is considered to be a sterol lipid molecule. 24,25-Dihydrolanosterol is considered to be a practically insoluble (in water) and relatively neutral molecule. Within the cell, 24,25-dihydrolanosterol is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, 24,25-dihydrolanosterol is involved in the simvastatin action pathway, the atorvastatin action pathway, the alendronate action pathway, and the ibandronate action pathway. 24,25-Dihydrolanosterol is also involved in several metabolic disorders, some of which include the chondrodysplasia punctata II, X linked dominant (CDPX2) pathway, the cholesteryl ester storage disease pathway, the mevalonic aciduria pathway, and lysosomal acid lipase deficiency (wolman disease). Outside of the human body, 24,25-dihydrolanosterol can be found in a number of food items such as yellow bell pepper, orange bell pepper, green bell pepper, and red bell pepper. This makes 24,25-dihydrolanosterol a potential biomarker for the consumption of these food products. 24,25-Dihydrolanosterol is involved in the biosynthesis of steriods. 24,25-Dihydrolanosterol is reversibly converted to lanosterol by delta24-sterol reductase [EC:1.3.1.72].


4,4-Dimethylcholesta-8,14,24-trienol is a product of the enzyme delta14-sterol reductase [EC 1.3.1.70] (KEGG). It is involved in the biosynthesis of steroids and is involved in the conversion of lanosterol to zymosterol. In particular, lanosterol 14-alpha-demethylase, catalyzes the C-14 demethylation of lanosterol to form 4,4-Dimethylcholesta-8,14,24-trienol in the ergosterol biosynthesis pathway. It is thought to be a meiosis activating sterol.

Follicular fluid meiosis activating sterol


4,4-Dimethyl-5a-cholesta-8,24-dien-3-b-ol (14-demethyllanosterol) is an intermediate in sterol biosynthesis. In particular, it is an intermediate in the conversion of lanosterol to zymosterol. 4,4-Dimethyl-5a-cholesta-8,24-dien-3-b-ol is a substrate for C-4 methyl sterol oxidase, NAD(P)-dependent steroid dehydrogenase, Cytochrome P450 51A1 and Delta(14)-sterol reductase.

4,4-dimethyl-5 alpha -cholesta-8,24-dien-3 beta -ol


4,4-Dimethyl-5a-cholesta-8-en-3b-ol belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing six isoprene units. 4,4-Dimethyl-5a-cholesta-8-en-3b-ol is considered to be a practically insoluble (in water) and relatively neutral molecule. Within the cell, 4,4-dimethyl-5a-cholesta-8-en-3b-ol is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, 4,4-dimethyl-5a-cholesta-8-en-3b-ol is involved in steroid biosynthesis pathway, the alendronate action pathway, the risedronate action pathway, and the simvastatin action pathway. 4,4-Dimethyl-5a-cholesta-8-en-3b-ol is also involved in several metabolic disorders, some of which include the hypercholesterolemia pathway, the wolman disease pathway, lysosomal acid lipase deficiency (wolman disease), and the smith-lemli-opitz syndrome (slos) pathway. 4,4-Dimethyl-5alpha-cholesta-8-en-3beta-ol is involved in the biosynthesis of steriods. 4,4-Dimethyl-5alpha-cholesta-8-en-3beta-ol is reversibly converted into 14-Demethyllanosterol by delta24-sterol reductase [EC:1.3.1.72].


4a-Methylzymosterol-4-carboxylic acid belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing six isoprene units. 4a-Methylzymosterol-4-carboxylic acid is considered to be a practically insoluble (in water) and relatively neutral molecule. Within the cell, 4a-methylzymosterol-4-carboxylic acid is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, 4a-methylzymosterol-4-carboxylic acid is involved in the desmosterolosis pathway, the rosuvastatin action pathway, the atorvastatin action pathway, and the alendronate action pathway. 4a-Methylzymosterol-4-carboxylic acid is also involved in several metabolic disorders, some of which include the cholesteryl ester storage disease pathway, the chondrodysplasia punctata II, X linked dominant (CDPX2) pathway, the hypercholesterolemia pathway, and the mevalonic aciduria pathway. 4alpha-Methylzymosterol-4-carboxylic acid is a steroid derivative involved in steroid biosynthesis. It is generated from 14-demethyl-lanosterol via the enzyme methylsterol monooxygenase (EC 1.14.13.72).


4a-Methylzymosterol is an intermediate in the biosynthesis of steroids (KEGG ID C05103). It is the 7th to last step in the synthesis of vitamin D2 and is converted from 3-keto-4-methtylzymosterol via the enzyme 3-keto steroid reductase [EC:1.1.1.270]. It is then converted to zymosterol. (KEGG).


zymosterol

Zymosterol is the precursor of cholesterol and is found in the plasma membrane. zymosterol circulates within the cells. The structural features of zymosterol provided optimal substrate acceptability. In human fibroblasts, zymosterol is converted to cholesterol solely in the rough ER. Little or no zymosterol or cholesterol accumulates in the rough ER in vivo. Newly synthesized zymosterol moves to the plasma membrane without a detectable lag and with a half-time of 9 min, about twice as fast as cholesterol. The pool of radiolabeled zymosterol in the plasma membrane turns over rapidly, faster than does intracellular cholesterol. Thus, plasma membrane zymosterol is not stagnant. [3H]Zymosterol pulsed into intact cells is initially found in the plasma membrane. (PMID: 1939176).


5alpha-Cholesta-7,24-dien-3beta-ol is involved in the biosynthesis of steroids. 5alpha-Cholesta-7,24-dien-3beta-ol is reversibly converted to 5alpha-Cholest-7-en-3beta-ol by delta24-sterol reductase [EC:1.3.1.72]. 5alpha-Cholesta-7,24-dien-3beta-ol is also converted to zymosterol by cholestenol delta-isomerase [EC:5.3.3.5]. 5alpha-Cholesta-7,24-dien-3beta-ol is also converted to 7-Dehydrodesmosterol. 5a-Cholesta-7,24-dien-3b-ol is a substrate for 3-beta-hydroxysteroid-delta(8),delta(7)-isomerase.


zymostenol

5a-Cholest-8-en-3b-ol is a normal human metabolite and an intermediate of cholesterol synthesis. The concentrations of zymostenol are higher, both in serum and bile of patients with cerebrotendinous xanthomatosis, compared to controls or in patients with cerebrotendinous xanthomatosis treated with chenodeoxycholic acid. Kidney transplant recipients had lower serum zymostenol when compared to controls. During consumption of plant stanol ester spread by hypercholesterolemic children, plant sterols in the plasma decrease and cholesterol precursor sterols such as zymostenol increase. (PMID: 15736111, 16709621, 16477216, 12756385).


lathosterol

Lathosterol is a a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. It is used as an indicator of whole-body cholesterol synthesis (PMID 14511438). Plasma lathosterol levels are significantly elevated in patients with bile acid malabsorption (PMID: 8777839). Lathosterol oxidase (EC 1.14.21.6) is an enzyme that catalyzes the chemical reaction 5alpha-cholest-7-en-3beta-ol + NAD(P)H + H+ + O2 cholesta-5,7-dien-3beta-ol + NAD(P)+ + 2 H2O.


7-Dehydrodesmosterol is a sterol intermediate in the biosynthesis of steroids. 7-Dehydrodesmosterol is a substrate of the enzyme 24-dehydrocholesterol reductase (EC:1.3.1.72), an important enzyme in the biosynthesis of Cholesterol. Cholesterol is synthesized from either Lathosterol, 7-Dehydrocholesterol, Desmosterol or Cholestenol by the enzyme 3beta-hydroxysterol delta7 reductase (EC 1.3.1.21, Dhcr7). The Smith-Lemli-Opitz syndrome (SLOS, OMIM 270400) is caused by a genetic defect in cholesterol biosynthesis; mutations in the enzyme 3beta-hydroxysterol delta7 reductase lead to a failure of cholesterol synthesis, with an accumulation of precursor sterols, such as 7-Dehydrodesmosterol. SLOS results in craniofacial, limb as well as major organ defects, including the brain. In individuals with this syndrome, mental retardation, as well as other CNS dysfunction, is almost 100% prevalent. (PMID: 15862627, 17197219).


7-Dehydrocholesterol is a zoosterol (a sterol produced by animals rather than plants). It is a provitamin-D. The presence of this compound in skin enables humans to manufacture vitamin D3 from ultraviolet rays via an intermediate isomer provitamin D3. It is also found in breast milk.


Cholesterol

Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues and transported in the blood plasma of all animals. The name originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol. This is because researchers first identified cholesterol in solid form in gallstones in 1784. In the body, cholesterol can exist in either the free form or as an ester with a single fatty acid (of 10-20 carbons in length) covalently attached to the hydroxyl group at position 3 of the cholesterol ring. Due to the mechanism of synthesis, plasma cholesterol esters tend to contain relatively high proportions of polyunsaturated fatty acids. Most of the cholesterol consumed as a dietary lipid exists as cholesterol esters. Cholesterol esters have a lower solubility in water than cholesterol and are more hydrophobic. They are hydrolyzed by the pancreatic enzyme cholesterol esterase to produce cholesterol and free fatty acids. Cholesterol has vital structural roles in membranes and in lipid metabolism in general. It is a biosynthetic precursor of bile acids, vitamin D, and steroid hormones (glucocorticoids, estrogens, progesterones, androgens and aldosterone). In addition, it contributes to the development and functioning of the central nervous system, and it has major functions in signal transduction and sperm development. Cholesterol is a ubiquitous component of all animal tissues where much of it is located in the membranes, although it is not evenly distributed. The highest proportion of unesterified cholesterol is in the plasma membrane (roughly 30-50% of the lipid in the membrane or 60-80% of the cholesterol in the cell), while mitochondria and the endoplasmic reticulum have very low cholesterol contents. Cholesterol is also enriched in early and recycling endosomes, but not in late endosomes. The brain contains more cholesterol than any other organ where it comprises roughly a quarter of the total free cholesterol in the human body. Of all the organic constituents of blood, only glucose is present in a higher molar concentration than cholesterol. Cholesterol esters appear to be the preferred form for transport in plasma and as a biologically inert storage (de-toxified) form. They do not contribute to membranes but are packed into intracellular lipid particles. Cholesterol molecules (i.e. cholesterol esters) are transported throughout the body via lipoprotein particles. The largest lipoproteins, which primarily transport fats from the intestinal mucosa to the liver, are called chylomicrons. They carry mostly triglyceride fats and cholesterol that are from food, especially internal cholesterol secreted by the liver into the bile. In the liver, chylomicron particles give up triglycerides and some cholesterol. They are then converted into low-density lipoprotein (LDL) particles, which carry triglycerides and cholesterol on to other body cells. In healthy individuals, the LDL particles are large and relatively few in number. In contrast, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. (Lack of information on LDL particle number and size is one of the major problems of conventional lipid tests.). In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease. There is a worldwide trend to believe that lower total cholesterol levels tend to correlate with lower atherosclerosis event rates (though some studies refute this idea). As a result, cholesterol has become a very large focus for the scientific community trying to determine the proper amount of cholesterol needed in a healthy diet. However, the primary association of atherosclerosis with cholesterol has always been specifically with cholesterol transport patterns, not total cholesterol per se. For example, total cholesterol can be low, yet made up primarily of small LDL and small HDL particles and atheroma growth rates are high. In contrast, however, if LDL particle number is low (mostly large particles) and a large percentage of the HDL particles are large (HDL is actively reverse transporting cholesterol), then atheroma growth rates are usually low, even negative, for any given total cholesterol concentration. These effects are further complicated by the relative concentration of asymmetric dimethylarginine (ADMA) in the endothelium since ADMA down-regulates production of nitric oxide, a relaxant of the endothelium. Thus, high levels of ADMA, associated with highly oxidized levels of LDL, pose a heightened risk factor for vascular disease. Chronically high levels of cholesterol are associated with at least five inborn errors of metabolism, including cerebrotendinous xanthomatosis, cholesteryl ester storage disease, congenital lipoid adrenal hyperplasia, hypercholesterolemia, and Zellweger syndrome. In chronically high levels, cholesterol can function as an atherogen (causes atherosclerosis and cardiovascular disease). Specifically, chronically high levels (from diet or from genetic predisposition or from diseases such as hyperlipidemia) of cholesterol and cholesterol esters lead to an excess of low-density lipoprotein (LDL) particles. In healthy individuals, the LDL particles are large and relatively few in number. In contrast, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease. Resistin, a protein secreted by fat tissue, has been shown to increase the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear cholesterol from the bloodstream. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease.


desmosterol

Desmosterol is an intermediate in the synthesis of cholesterol. Desmosterolosis is a rare autosomal recessive inborn errors of cholesterol synthesis that is caused by defective activity of desmosterol reductase which results in an accumulation of demosterol (DHCR24, EC 1.3.1.72), combines a severe osteosclerotic skeletal dysplasia and includes 2-3 toe syndactyly with Smith-Lemli-Opitz syndrome (SLOS; the biochemical block in SLOS results in decreased cholesterol levels and increased 7-dehydrocholesterol levels). Desmosterolosis is caused by mutation of the 24-dehydrocholesterol reductase gene (DHCR24). Many of the malformations in SLOS and desmosterolosis are consistent with impaired hedgehog function. The hedgehog proteins include Sonic hedgehog (SHH), which plays a major role in midline patterning and limb development. Desmosterolosis, caused by defective activity of desmosterol reductase, combines a severe osteosclerotic skeletal dysplasia. 7-dehydrocholesterol reductase (DHCR7, EC 1.3.1.21) reduces the C7-C8 double bond in the sterol B ring to form cholesterol or desmosterol depending upon the precursor. Desmosterol can be converted to cholesterol by DHCR24. Therefore, SLOS and Desmosterolosis patients invariably have elevated levels of cholesterol precursor's 7-dehydrocholesterol (and its spontaneous isomer 8-dehydrocholesterol) and absent desmosterol. (PMID: 14631207, 16207203).


Ergocalciferol

Vitamin D3, also called cholecalciferol, is one of the forms of vitamin D. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of Vitamin A. It is structurally similar to steroids such as testosterone, cholesterol, and cortisol (although vitamin D3, itself, is a secosteroid). Vitamin D3 is a derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking the C9-C10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24. Vitamin D3 can also come from dietary sources, such as beef liver, cheese, egg yolks, and fatty fish (PubChem). The first step involved in the activation of vitamin D3 is a 25-hydroxylation catalyzed by 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyzes the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by (1) increasing GI absorption of phosphorus and calcium, (2) increasing osteoclastic resorption, and (3) increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through the formation of a calcium-binding protein.


Leucine

Branched chain amino acids (BCAA) are essential amino acids whose carbon structure is marked by a branch point. These three amino acids are critical to human life and are particularly involved in stress, energy and muscle metabolism. BCAA supplementation as therapy, both oral and intravenous, in human health and disease holds great promise. 'BCAA' denotes valine, isoleucine and leucine which are branched chain essential amino acids. Despite their structural similarities, the branched amino acids have different metabolic routes, with valine going solely to carbohydrates, leucine solely to fats and isoleucine to both. The different metabolism accounts for different requirements for these essential amino acids in humans: 12 mg/kg, 14 mg/kg and 16 mg/kg of valine, leucine and isoleucine respectively. Furthermore, these amino acids have different deficiency symptoms. Valine deficiency is marked by neurological defects in the brain, while isoleucine deficiency is marked by muscle tremors. Many types of inborn errors of BCAA metabolism exist, and are marked by various abnormalities. The most common form is the maple syrup urine disease, marked by a characteristic urinary odor. Other abnormalities are associated with a wide range of symptoms, such as mental retardation, ataxia, hypoglycemia, spinal muscle atrophy, rash, vomiting and excessive muscle movement. Most forms of BCAA metabolism errors are corrected by dietary restriction of BCAA and at least one form is correctable by supplementation with 10 mg of biotin daily. BCAA are useful because they are metabolized primarily by muscle. Stress state- e.g surgery, trauma, cirrhosis, infections, fever and starvation--require proportionately more BCAA than other amino acids and probably proportionately more leucine than either valine or isoleucine. BCAA and other amino acids are frequently fed intravenously (TPN) to malnourished surgical patients and in some cases of severe trauma. BCAA, particularly leucine, stimulate protein synthesis, increase reutilization of amino acids in many organs and reduce protein breakdown. Furthermore, leucine can be an important source of calories, and is superior as fuel to the ubiquitous intravenous glucose (dextrose). Leucine also stimulates insulin release, which in turn stimulates protein synthesis and inhibits protein breakdown. These effects are particularly useful in athletic training. BCAA should also replace the use of steroids as commonly used by weightlifters. Huntington's chorea and anorexic disorders both are characterized by low serum BCAA. These diseases, as well as forms of Parkinson's, may respond to BCAA therapy. BCAA, and particularly leucine, are among the amino acids most essential for muscle health. (http://www.dcnutrition.com).


Ketoleucine

Ketoleucine is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids. Ketoleucine is both a neurotoxin and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of ketoleucine are associated with maple syrup urine disease (MSUD). MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The symptoms of MSUD often show in infancy and lead to severe brain damage if untreated. MSUD may also present later depending on the severity of the disease. If left untreated in older individuals, during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme, or erratic behaviour and moods, hallucinations, anorexia, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma.  In maple syrup urine disease, the brain concentration of branched-chain ketoacids can increase 10- to 20-fold. This leads to a depletion of glutamate and a consequent reduction in the concentration of brain glutamine, aspartate, alanine, and other amino acids. The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis (PMID: 15930465).

2-keto-4-methylvalerate
2-keto-4-methylvaleric acid
2-ketoisocaproate
2-ketoisocaproic acid
2-oxo-4-methylpentanoate
2-oxo-4-methylpentanoic acid
2-oxo-4-methylvalerate
2-oxo-4-methylvaleric acid
2-oxoisocaproate
2-oxoisocaproic acid
2-oxoleucine
4-methyl-2-oxo-valerate
4-methyl-2-oxo-valeric acid
4-methyl-2-oxopentanoate
4-methyl-2-oxopentanoic acid
Ketoisocaproate
Ketoisocaproic acid
Methyloxovalerate
Methyloxovaleric acid
Oxoisocaproate
Oxoisocaproic acid
A-ketoisocaproate
A-ketoisocaproic acid
A-ketoisocapronate
A-ketoisocapronic acid
A-oxoisocaproate
A-oxoisocaproic acid
Alpha-keto-isocaproate
Alpha-keto-isocaproic acid
Alpha-ketoisocaproate
Alpha-ketoisocaproic acid
Alpha-ketoisocapronate
Alpha-ketoisocapronic acid
Alpha-oxoisocaproate
Alpha-oxoisocaproic acid
Keto-leucine


3-Methyl-1-hydroxybutyl-ThPP is an intermediate in valine, leucine and isoleucine degradation(KEGG ID C15974). It is the second to last step in the synthesis of 3-methylbutanoyl-CoA and is converted from 4-methyl-2-oxopentanoate via the enzyme 2-oxoisovalerate dehydrogenase [EC:1.2.4.4]. It is then converted to S-(3-methylbutanoyl)-dihydrolipoamide-E via the enzyme 2-oxoisovalerate dehydrogenase [EC:1.2.4.4].


S-(3-Methylbutanoyl)-dihydrolipoamide-E is an intermediate in valine, leucine and isoleucine degradation(KEGG ID C15975 ). It is the second to last step in the synthesis of branched chain fatty acid and is converted from 3-methyl-hydroxybutyl-ThPP via the enzyme 2-oxoisovalerate dehydrogenase [EC:1.2.4.4]. It is then converted to 3-methylbutanoyl-CoA via the enzyme dihydrolipoyllysine-residue (2-methylpropanoyl)transferase[EC:2.3.1.168].


isovaleryl-CoA

Isovaleryl-CoA is an intermediate metabolite in the catabolic pathway of leucine. The accumulation of derivatives of isovaleryl-CoA occurs in patients affected with isovaleric acidemia (IVA, OMIM 243500) an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (IVD, EC 1.3.99.10, a flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA). IVA was the first organic acidemia recognized in humans and can cause significant morbidity and mortality. Early diagnosis and treatment with a protein restricted diet and supplementation with carnitine and glycine are effective in promoting normal development in severely affected individuals. Both intra- and interfamilial variability have been recognized. Initially, two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. More recently, a third group of individuals with mild biochemical abnormalities who can be asymptomatic have been identified through newborn screening of blood spots by tandem mass spectrometry. The majority of patients with IVA today are diagnosed pre-symptomatically through newborn screening by use of MS/MS which reveals elevations of the marker metabolite C5 acylcarnitine in dried blood spots. C5 acylcarnitine represents a mixture of isomers (isovalerylcarnitine, 2-methylbutyrylcarnitine, and pivaloylcarnitine). (PMID: 16602101, Am J Med Genet C Semin Med Genet. 2006 May 15;142(2):95-103.).

3-methylbutanoyl-coa
3-methylbutanoyl-coenzyme a
3-methylbutyryl-coa
3-methylbutyryl-coenzyme a
Isovaleryl coa
Isovaleryl coenzyme a
Isovaleryl-coenzyme a
S-(3-methylbutanoate
S-(3-methylbutanoate) coenzyme a
S-(3-methylbutanoic acid
S-isovalerate coa
S-isovalerate coenzyme a


dihydrolipoamide

Dihydrolipoamide is an intermediate in glycolysis/gluconeogenesis, citrate cycle (TCA cycle), alanine, aspartate and pyruvate metabolism, and valine, leucine and isoleucine degradation (KEGG ID C00579). It is converted to lipoamide via the enzyme dihydrolipoamide dehydrogenase [EC:1.8.1.4]. Dihydrolipoamide is also a substrate of enzyme Acyltransferases [EC 2.3.1.-]. (KEGG).


3-Methylcrotonyl-CoA, also known as 3-methylbut-2-enoyl-CoA or dimethylacryloyl-CoA, belongs to the class of organic compounds known as acyl coas. These are organic compounds containing a coenzyme A substructure linked to an acyl chain. 3-Methylcrotonyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). 3-Methylcrotonyl-CoA has been primarily detected in urine. Within the cell, 3-methylcrotonyl-CoA is primarily located in the mitochondria and cytoplasm. 3-Methylcrotonyl-CoA exists in all living organisms, ranging from bacteria to humans. In humans, 3-methylcrotonyl-CoA is involved in the valine, leucine and isoleucine degradation pathway. 3-Methylcrotonyl-CoA is also involved in several metabolic disorders, some of which include Beta-ketothiolase deficiency, the propionic acidemia pathway, the 3-hydroxyisobutyric aciduria pathway, and 2-methyl-3-hydroxybutryl CoA dehydrogenase deficiency. 3-Methylcrotonyl-CoA is an essential metabolite for leucine metabolism, a substrate of 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4), a biotin-dependent mitochondrial enzyme in the catabolism of leucine. (OMIM 609010).


3-Methylglutaconyl-CoA belongs to the class of organic compounds known as acyl coas. These are organic compounds containing a coenzyme A substructure linked to an acyl chain. Thus, 3-methylglutaconyl-CoA is considered to be a fatty ester lipid molecule. 3-Methylglutaconyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). 3-Methylglutaconyl-CoA has been primarily detected in urine. Within the cell, 3-methylglutaconyl-CoA is primarily located in the mitochondria and cytoplasm. In humans, 3-methylglutaconyl-CoA is involved in the valine, leucine and isoleucine degradation pathway. 3-Methylglutaconyl-CoA is also involved in several metabolic disorders, some of which include 2-methyl-3-hydroxybutryl CoA dehydrogenase deficiency, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, the methylmalonic aciduria pathway, and the 3-methylglutaconic aciduria type III pathway. 3-Methylglutaconyl-CoA is a substrate for Methylglutaconyl-CoA hydratase (mitochondrial), Methylcrotonoyl-CoA carboxylase beta chain (mitochondrial) and Methylcrotonoyl-CoA carboxylase alpha chain (mitochondrial).