Phosphoric acid

Phosphoric acid, also known as orthophosphoric acid or phosphoric(V) acid, is a mineral acid with the chemical formula H3PO4. Alternatively, orthophosphoric acid molecules can combine with themselves to form a variety of compounds referred to as phosphoric acids in a more general way. For a discussion of these, see Phosphoric acids and Phosphates. Appears to exist only as a food additive and produced synthetically. --Wikipedia.

Sodium pyrophosphate decahydrate biochemica


Amikacin

Amikacin is a semi-synthetic aminoglycoside antibiotic derived from kanamycin A. Similar to other aminoglycosides, amikacin disrupts bacterial protein synthesis by binding to the 30S ribosome of susceptible organisms. Binding interferes with mRNA binding and tRNA acceptor sites leading to the production of non-functional or toxic peptides. Other mechanisms not fully understood may confer the bactericidal effects of amikacin. Amikacin is also nephrotoxic and ototoxic.


Amiloride

A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)


Amiodarone

Amiodarone is only found in individuals that have used or taken this drug. It is an antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [PubChem]The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.


selenocystathionine

Selenocystathionine is formed from Selenohomocysteine by the enzyme cystathionine beta-synthase (EC 4.2.1.22), as a by-product of cystathionine synthesis. Selenocystathionine is consumed in the diet, and is one of the main compounds present in plants that tend to hyperaccumulate selenium and use it as an elemental plant defense mechanism. (PMID: 10026151, 6456763, 16920881).


Amlodipine

Amlodipine is a long-acting calcium channel blocker used as an anti-hypertensive and in the treatment of angina. As other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing peripheral resistance and hence improving blood pressure; in angina it improves blood flow to the myocardium. It was developed under the direction of Dr. Simon Campbell; A long acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension; in angina it improves blood flow to the myocardium. Amlodipine (as besylate, mesylate or maleate) is a long-acting calcium channel blocker used as an anti hypertensive and in the treatment of angina. Amlodipine is marketed as Norvasc in North America and as Istin in the United Kingdom as well as under various other names. As other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing peripheral resistance and hence improving blood pressure; Amlodipine (as besylate, mesylate or maleate) is a long-acting calcium channel blocker used as an anti-hypertensive and in the treatment of angina. Amlodipine is marketed as Norvasc in North America and as Istin in the United Kingdom as well as under various other names. As other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing peripheral resistance and hence improving blood pressure; in angina it improves blood flow to the myocardium. It was developed under the direction of Dr. Simon Campbell.


Angiotensin II

Angiotensin II is a hormone that may act on the central nervous system to regulate renal sympathetic nerve activity, renal function, and, therefore, blood pressure. Angiotensin II is produced locally within the kidney and mediates tissue injury through a series of nonhemodynamic effects. angiotensin II is not only involved in the regulation of blood pressure, water and sodium homeostasis, and control of other neurohumoral systems, but also leads to excessive production of reactive oxygen species and to hypertrophy, proliferation, migration, and apoptosis of vascular cells. Angiotensin II is one of the main factors involved in hypertension-induced tissue damage. This peptide regulates the inflammatory process. Angiotensin II activates circulating cells, and participates in their adhesion to the activated endothelium and subsequent transmigration through the synthesis of adhesion molecules, chemokines and cytokines. Among the intracellular signals involved in angiotensin II-induced inflammation, the production of reactive oxygen species and the activation of nuclear factor-kappaB are the best known. Classical, well-defined actions of Angiotensin II in the brain include the regulation of hormone formation and release, the control of the central and peripheral sympathoadrenal systems, and the regulation of water and sodium intake. As a consequence of changes in the hormone, sympathetic and electrolyte systems, feedback mechanisms in turn modulate the activity of the brain Angiotensin II systems. There are two Angiotensin II systems in the brain. The discovery of brain Angiotensin II receptors located in neurons inside the blood brain barrier confirmed the existence of an endogenous brain Angiotensin II system, responding to Angiotensin II generated in and/or transported into the brain. In addition, Angiotensin II receptors in circumventricular organs and in cerebrovascular endothelial cells respond to circulating Angiotensin II of peripheral origin. Thus, the brain responds to both circulating and tissue Angiotensin II, and the two systems are integrated. (PMID: 17147923, 16672146, 16601568, 16481883, 16075377).


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.


vitamin B6

The 4-methanol form of vitamin B6 which is converted to pyridoxal phosphate which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990). Pyridoxine is one of the compounds that can be called vitamin B6. Pyridoxine assists in the balancing of sodium and potassium as well as promoting red blood cell production. It is linked to cancer immunity and helps fight the formation of homocysteine. It has been suggested that Pyridoxine might help children with learning difficulties, and may also prevent dandruff, eczema, and psoriasis. In addition, pyridoxine can help balance hormonal changes in women and aid in immune system. Lack of pyridoxine may cause anemia, nerve damage, seizures, skin problems, and sores in the mouth. -- Wikipedia Deficiency, though rare because of widespread distribution in foods, leads to the development of peripheral neuritis in adults and affects the central nervous system in children (DOSE - 3rd edition).


Zinc

Zinc is an essential element, necessary for sustaining all life. It is a trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen cell types in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system, and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature and shows that just micromolar amounts of the free ion kill some organisms.


Vinblastine

Vinblastine is only found in individuals that have used or taken this drug. It is an antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.


3alpha,7alpha,12alpha-Trihydroxy-5beta-24-oxocholestanoyl-CoA is an intermediate in bile acid synthesis. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


4-Imidazolone-5-propanoate is a metabolite of histidine metabolism. It is produced from urocanic acid by the enzyme urocanate hydratase [EC:4.2.1.49]. 4-Imidazolone-5-propionic acid can spontaneously decay to 4-oxoglutaramate or formylisoglutamine. It is also converted to N-forminimo-L-glutamate by the enzyme imidazolonepropionase [EC:3.5.2.7].


1-pyrroline-3-hydroxy-5-carboxylic acid

Pyrroline hydroxycarboxylic acid is a metabolite identified in the urine of patients with type II hyperprolinemia. (OMIM 239510). The urinary excretion of Pyrroline hydroxycarboxylic acid increased in hyperprolinemic patients but not in healthy controls during oral loading of hydroxyproline and hydroxyproline-ornithine. (PMID: 533224). Hyperprolinemia type II (HP II) is a rare inherited metabolic disease due to the deficiency of pyroline-5-carboxylate dehydrogenase. It is generally believed to be a benign condition although some patients have neurological problems such as refractory convulsions. (PMID: 15214748). The oxidation of pyrroline-carboxylate generates glutamate and pyrroline-hydroxycarboxylate, a reaction catalyzed by hydroxyproline oxidase (PMID: 500817).


3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoA is an intermediate involved in bile acid synthesis, specifically in the synthesis of chenodeoxyglycocholate. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


Imidazole-4-acetaldehyde is a naturally occurring aldehyde metabolite of histamine formed by the action of histaminase (E.C. 1.4.3.6), and can be synthesized by oxidation of histidine. Aldehyde dehydrogenase (EC 1.2.1.3) is the only enzyme in the human liver capable of catalyzing dehydrogenation of aldehydes arising via monoamine, diamine, and plasma amine oxidases. NAD-linked dehydrogenation of short chain aliphatic aldehydes has been found in virtually every organ of the mammalian body. Imidazole-4-acetaldehyde is a good substrate for all aldehyde dehydrogenase isozymes. Experimentally, the prebiotic formation of histidine has been accomplished by the reaction of erythrose with formamidine followed by a Strecker synthesis. Imidazole-4-acetaldehyde could have been converted to histidine on the primitive earth by a Strecker synthesis, and several prebiotic reactions could convert imidazole-4-glycol and imidazole-4-ethanol to imidazole-4-acetaldehyde. (PMID: 2071588, 2957640, 11536478).


(S)-3-Hydroxyhexadecanoyl-CoA is a beta-oxidation intermediate derivative of palmitoyl-CoA and the substrate of the enzyme peroxisomal acyl-CoA thioesterase 2 (PTE-2, EC 3.1.2.2), which is localized in the peroxisome. The peroxisomal beta-oxidation system contains two sets of enzymes, one of which is involved in the oxidation of branched chain fatty acids and intermediates in the hepatic bile acid biosynthetic pathway and consists of one or two branched-chain acyl-CoA oxidase(s), a D-specific bifunctional protein and the sterol carrier-like protein x (SCPx). Peroxisomes are cellular organelles present in all eukaryotic cells. They play an indispensable role in the metabolism of a variety of lipids including very long-chain fatty acids, dicarboxylic fatty acids, bile acids, prostaglandins, leukotrienes, thromboxanes, pristanic acid, and xenobiotic fatty acids. (S)-3-Hydroxyhexadecanoyl-CoA may accumulate intracellularly in certain long-chain fatty acid/j-oxidation deficiencies. Succinate-driven synthesis of ATP from ADP and phosphate is progressively inhibited by increasing concentrations of (S)-3-Hydroxyhexadecanoyl-CoA. (PMID: 11673457, 8739955, 7662716).

(s)-3-hydroxyhexadecanoyl-coenzyme a
(s)-3-hydroxypalmitoyl-coenzyme a
Dl-3-hydroxyhexadecanoyl-s-coenzyme a
Dl-3-hydroxyhexadecanoyl-scoa
Dl-3-hydroxyhexadecanoyl-scoenzyme a
S-(3-hydroxyhexadecanoate
S-(3-hydroxyhexadecanoate)coenzyme a
S-(3-hydroxyhexadecanoic acid
S-dl-3-hydroxyhexadecanoate
S-dl-3-hydroxyhexadecanoic acid
B-hydroxypalmitoyl-coa
B-hydroxypalmitoyl-coenzyme a
Beta-hydroxypalmitoyl-coa
Beta-hydroxypalmitoyl-coenzyme a


3 alpha,7 alpha,24-Trihydroxy-5beta-cholestanoyl-CoA is found in the primary bile acid biosynthesis pathway. 3 alpha,7 alpha,24-Trihydroxy-5beta-cholestanoyl-CoA is created from 3 alpha,7 alpha-Dihydroxy-5beta-cholest-24-enoyl-CoA through the action of HSD17B4 (EC4.2.1.107). 3 alpha,7 alpha,24-Trihydroxy-5beta-cholestanoyl-CoA is then converted to 3 alpha,7 alpha-Dihydroxy-5beta-24-oxocholestanoyl-CoA by HSD17B4 (EC1.1.1.35).


DIHYDROXYINDOLE

5,6-Dihydroxyindole, also known as DHI or dopamine lutine, belongs to the class of organic compounds known as hydroxyindoles. These are organic compounds containing an indole moiety that carries a hydroxyl group. 5,6-Dihydroxyindole is slightly soluble (in water) and a very weakly acidic compound (based on its pKa). In humans, 5,6-dihydroxyindole is involved in the tyrosine metabolism pathway and the disulfiram action pathway. 5,6-Dihydroxyindole is also involved in several metabolic disorders, some of which include tyrosinemia, transient, OF the newborn pathway, monoamine oxidase-a deficiency (mao-a), the tyrosinemia type I pathway, and the alkaptonuria pathway. 5,6-Dihydroxyindole is a substrate for Tyrosinase.

Aminochrome
Dhi
Dopaminochrome
Dopamine lutine


Indole-5,6-quinone, also known as IQ, belongs to the class of organic compounds known as indoles and derivatives. These are organic compounds containing an indole, which is a bicyclic ring system made up of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole-5,6-quinone is soluble (in water) and a strong basic compound (based on its pKa). In humans, indole-5,6-quinone is involved in the tyrosine metabolism pathway and the disulfiram action pathway. Indole-5,6-quinone is also involved in several metabolic disorders, some of which include the alkaptonuria pathway, the hawkinsinuria pathway, dopamine beta-hydroxylase deficiency, and monoamine oxidase-a deficiency (mao-a). Indole-5,6-quinone is involved in the tyrosine metabolism pathway. More specifically, indole-5,6-quinone is an intermediate in the production of melanin. Indole-5,6-quinone is produced from 5,6-dihydroxyindole by tyrosinase [EC:1.14.18.1].

1h-indole-5,6-dione
Indole-5,6 quinone
Iq
Indolequinone


NUDIFLORAMIDE

N-methyl-2-pyridone-5-carboxamide (2PY) is one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation. Increased serum 2PY concentrations are observed in chronic renal failure (CRF) patients, which along with the deterioration of kidney function and its toxic properties (significant inhibition of PARP-1), suggests that 2PY is an uremic toxin. (PMID 12694300).


3alpha,7alpha-Dihydroxy-5beta-cholestan-26-al is an intermediate involved in bile acid biosynthesis, specifically in the synthesis of chenodeoxyglycocholate and lithocholate. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


linolenic acid

Alpha-linolenic acid (ALA) is a polyunsaturated fatty acid (PUFA). It is a member of the group of essential fatty acids called omega-3 fatty acids. Alpha-linolenic acid, in particular, is not synthesized by mammals and therefore is an essential dietary requirement for all mammals. Certain nuts (English walnuts) and vegetable oils (canola, soybean, flaxseed/linseed, olive) are particularly rich in alpha-linolenic acid (ALA). Omega-3 fatty acids get their name based on the location of one of their first double bond. In all omega-3 fatty acids, the first double bond is located between the third and fourth carbon atom counting from the methyl end of the fatty acid (n-3). Although humans and other mammals can synthesize saturated and some monounsaturated fatty acids from carbon groups in carbohydrates and proteins, they lack the enzymes necessary to insert a cis double bond at the n-6 or the n-3 position of a fatty acid. Omega-3 fatty acids like a-linolenic acid are important structural components of cell membranes. When incorporated into phospholipids, they affect cell membrane properties such as fluidity, flexibility, permeability and the activity of membrane bound enzymes. Omega-3 fatty acids can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation. Alpha linolenic acid and other omega 3 fatty acids may regulate gene expression by interacting with specific transcription factors, including peroxisome proliferator activated receptors (PPARs) and liver X receptors (LXRs).


N-acetylneuraminic acid 9-phosphate

N-Acetylneuraminate 9-phosphate is an intermediate in Aminosugars metabolism. N-Acetylneuraminate 9-phosphate is the 4th to last step in the synthesis of colominate and is converted from N-Acetyl-D-mannosamine-6-phosphate via the enzyme N-Acylneuraminate-9-phosphate synthase (EC 2.5.1.57). It is then converted to N-Acetylneuraminate via the enzyme N-acylneuraminate-9-phosphatase(EC 3.1.3.29).


3a,7a,12a,24-Tetrahydroxy-5b-cholestanoyl-CoA is an intermediate in bile acid synthesis. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


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].


(S)-3-Hydroxytetradecanoyl-CoA is an intermediate in Fatty acid elongation in mitochondria. (S)-3-Hydroxytetradecanoyl-CoA is the 7th to last step in the synthesis of Hexadecanoic acid and is converted from 3-Oxotetradecanoyl-CoA via the enzyme long-chain 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.211). It is then converted to trans-Tetradec-2-enoyl-CoA via the enzyme enoyl-CoA hydratase (EC 4.2.1.17).


Dihydrothymine

Dihydrothymine is an intermediate breakdown product of thymine. Dihydropyrimidine dehydrogenase catalyzes the reduction of thymine into 5,6-dihydrothymine then dihydropyrimidinase hydrolyzes 5,6-dihydrothymine into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine to beta-alanine. When present at abnormally high levels, dihydrothymine can be toxic, although the mechanism of toxicity is not clear. In particular, patients with dihydropyrimidinase deficiency exhibit highly increased concentrations of 5,6-dihydrouracil and 5,6-dihydrothymine, and moderately increased concentrations of uracil and thymine can be detected in urine. Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. The most common neurological abnormalities that occur are intellectual disability, seizures, weak muscle tone (hypotonia), abnormally small head size (microcephaly), and autistic behaviours that affect communication and social interaction. Gastrointestinal problems that occur in dihydropyrimidinase deficiency include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting.


Folic acid

Folic acid is a member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (poaceae). Folic acid, being biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylated tRNA, and generate and use formate. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.


glycodeoxycholic acid

Deoxycholic acid glycine conjugate, or Deoxygcholylglycine, is an acyl glycine and a bile acid-glycine conjugate. It is a secondary bile acid produced by the action of enzymes existing in the microbial flora of the colonic environment. In hepatocytes, both primary and secondary bile acids undergo amino acid conjugation at the C-24 carboxylic acid on the side chain, and almost all bile acids in the bile duct therefore exist in a glycine conjugated form (PMID:16949895). As a bile salt it acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic.


uroporphyrin I

Uroporphyrin is the porphyrin produced by oxidation of the methylene bridges in uroporphyrinogen. Uroporphyrins have four acetic acid and four propionic acid side chains attached to their pyrrole rings. The enzyme uroporphyrinogen I synthase catalyzes the formation of hydroxymethylbilane from four molecules of porphobilinogen. Uroporphyrinogen III cosynthase then catalyzes the conversion of hydroxymethylbilane into uroporphyrinogen III. Otherwise, hydroxymethylbilane cyclizes nonenzymatically to form uroporphyrinogen I. Uroporphyrinogen I and III yield their respective uroporphyrins via autooxidation or their respective coproporphyrinogens via decarboxylation. Excessive amounts of uroporphyrin I are excreted in congenital erythropoietic porphyria, and both uroporphyrin I and uroporphyrin III are excreted in porphyria cutanea tarda. Uroporphyrin I and III are the most common isomers. Under certain conditions, uroporphyrin I can act as a phototoxin, a neurotoxin, and a metabotoxin. A phototoxin leads to cell damage upon exposure to light. 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 porphyrins are associated with porphyrias such as porphyria variegate, acute intermittent porphyria, porphyria cutanea tarda, and hereditary coproporphyria (HCP). There are several types of porphyrias (most are inherited). Hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems (usually a light-sensitive blistering rash and increased hair growth). The neurotoxicity of porphyrins may be due to their selective interactions with tubulin, which disrupt microtubule formation and cause neural malformations (PMID: 3441503).


Prostaglandin J2 (PGJ2) is an endogenous product of inflammation in humans. It induces neuronal death and the accumulation of ubiquitinated proteins into distinct aggregates. It may play a role in neurodegenerative disorders inducing a chain of events that culminates in neuronal cell death. An altered expression of enzymes in PGJ2 synthesis may represent a novel pathogenic mechanism in human obesity. The peroxisome proliferator-activated receptor gamma (PPARγ) has a fundamental role in glucose homeostasis and adipocyte differentiation. Besides linoleate, linolenate and arachidonate, the most notable PPAR ligand is 15-deoxy-delta12-14-prostaglandin J2, a natural derivative of prostaglandin D2 and PGJ2. It is therefore plausible that the production of 15d-PGJ2 within adipose tissue may act as an endogenous mediator of adipocyte differentiation. PGJ2 disrupts the cytoskeleton in neuronal cells. This cyclopentenone prostaglandin triggered endoplasmic reticulum (ER) collapse and the redistribution of ER proteins, such as calnexin and catechol-O-methyltransferase, into a large centrosomal aggregate containing ubiquitinated proteins and alpha-synuclein. The PGJ2-dependent cytoskeletal rearrangement paralleled the development of the large centrosomal aggregate. Supporting a mechanism by which, upon PGJ2 treatment, cytoskeleton/ER collapse coincides with the relocation of ER proteins, other potentially neighboring proteins, and ubiquitinated proteins into centrosomal aggregates. Development of these large perinuclear aggregates is associated with disruption of the microtubule/ER network. This aberrant protein deposition, triggered by a product of inflammation, may be common to other compounds that disrupt microtubules and induce protein aggregation, such as MPP+ and rotenone, found to be associated with neurodegeneration. Many neurodegenerative disorders, such as Parkinson disease, exhibit inclusion bodies containing ubiquitinated proteins. Concentrations of PGJ2 in biofluids have not been established, since this prostaglandin is further metabolized into delta12-PGJ2, and 15-deoxy-delta12,14-PGJ2. (PMID: 16737963, 16842938, 16774923)Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoA is an intermediate in bile acid synthesis. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


melibiitol

Melibiitol belongs to the class of organic compounds known as fatty acyl glycosides of mono- and disaccharides. Fatty acyl glycosides of mono- and disaccharides are compounds composed of a mono- or disaccharide moiety linked to one hydroxyl group of a fatty alcohol or of a phosphorylated alcohol (phosphoprenols), a hydroxy fatty acid or to one carboxyl group of a fatty acid (ester linkage) or to an amino alcohol. Melibiitol is soluble (in water) and a very weakly acidic compound (based on its pKa). Melibiitol has been primarily detected in urine. Within the cell, melibiitol is primarily located in the cytoplasm. In humans, melibiitol is involved in the galactose metabolism pathway. Melibiitol is also involved in the metabolic disorder called the galactosemia pathway. Melibitol is involved in galactose metabolism. D-galactose and D-sorbitol are combined to form melibitol through the action of alpha-galactosidase [EC:3.2.1.22]. It is a reversible reaction.


(2E)-Octenoyl-CoA is the main metabolite produced in medium-chain acyl-CoA dehydrogenase (EC 1.3.99.3, MCAD) deficiency; however the product of the enzymatic reaction is not directly detected in several methods for screening of inborn errors of fatty acid oxidation. In order to aid the timely follow-up of screening results that suggest abnormalities in MCAD, rapid and simple confirmatory tests for the enzyme activity and/or gene mutation analysis should be available. Medium-chain fatty acyl-CoA dehydrogenase (MCAD) catalyzes the conversion of different chain length fatty acyl- CoAs into their corresponding trans-enoyl-CoA moieties via two consecutive sequences of steps. The first step involves the concerted abstraction of a proton and a hydride ion from the a- and 8-carbon chains of the fatty acyl-CoA substrates, concomitant with the reduction of the enzyme (E)-bound FAD to FADH2. The reoxidation of EFADH2, to propagate further rounds of catalysis, is accomplished via transfer of electrons to a variety of organic electron acceptors; the natural electron acceptor for this process, under physiological conditions, is the electron-transferring flavoprotein. Of the different chain length fatty acyl-CoA substrates, octanoyl-CoA/octenoyl-CoA have been known as the most efficient (and physiological) substrates for the medium-chain fatty acyl-CoA dehydrogenase (MCAD)-catalyzed reaction. (PMID: 16046200, 1390638, 8038175).

(e)-s-2-octenoate
(e)-s-2-octenoate coa
(e)-s-2-octenoate coenzyme a
(e)-s-2-octenoic acid
2,3-trans-octenoyl coenzyme a
Oct-2-trans-enoyl-coa
Oct-2-trans-enoyl-coenzyme a
Oct-trans-2-enoyl coenzyme a
S-(2e)-2-octenoate
S-(2e)-2-octenoate coa
S-(2e)-2-octenoate coenzyme a
S-(2e)-2-octenoic acid
Trans-d2,3-octenoyl-coa
Trans-d2,3-octenoyl-coenzyme a
Trans-oct-2-enoyl-coa
Trans-oct-2-enoyl-coenzyme a


Hexanoyl-CoA

Hexanoyl-CoA, also known as hexanoyl-coenzyme A or caproyl-CoA, is a medium-chain fatty acyl-CoA having hexanoyl as the acyl group. Hexanoyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). Within the cell, hexanoyl-CoA is primarily located in the membrane (predicted from logP). It can also be found in the extracellular space. Hexanoyl-CoA exists in all living organisms, ranging from bacteria to humans. In humans, hexanoyl-CoA is involved in the biosynthesis and oxidation of fatty acids as well as in ceramide formation. Hexanoyl-CoA is also involved in few metabolic disorders, such as fatty acid elongation in mitochondria, mitochondrial beta-oxidation of medium chain saturated fatty acids, and mitochondrial beta-oxidation of short chain saturated fatty acids.

Caproyl-CoA
Caproyl coenzyme A
Caproyl-coenzyme A
Hexanoyl coenzyme A
Hexanoyl-coenzyme A
CoA(6:0)


prostaglandin C2

Prostaglandin-C2, also known as PGC2, 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. Thus, prostaglandin-C2 is considered to be an eicosanoid lipid molecule. Prostaglandin-C2 is considered to be a practically insoluble (in water) and relatively neutral molecule. Prostaglandin-C2 has been primarily detected in urine. Within the cell, prostaglandin-C2 is primarily located in the membrane (predicted from logP) and cytoplasm. In humans, prostaglandin-C2 is involved in the nabumetone action pathway, the antrafenine action pathway, the phenylbutazone action pathway, and the trisalicylate-choline action pathway. Prostaglandin-C2 is also involved in a couple of metabolic disorders, which include leukotriene C4 synthesis deficiency and the tiaprofenic Acid action pathway. This compound belongs to the family of Prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.


20-hydroxy-20-oxoleukotriene B4

20-Carboxyleukotriene B4 is an omega-oxidized metabolite of leukotriene B4 (LTB4). Neutrophil microsomes are known to oxidize 20-hydroxy-LTB4 (20-OH-LTB4) to its 20-oxo and 20-carboxy derivatives in the presence of NADPH. This activity has been ascribed to LTB4 omega-hydroxylase (cytochrome P-450LTB omega). Leukotriene B4 release from polymorphonuclear granulocytes of severely burned patients was reduced as compared to healthy donor cells. This decrease is due to an enhanced conversion of LTB4 into the 20-hydroxy- and 20-carboxy-metabolites and further to a decreased LTB4-synthesis. LTB4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/ 15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. (PMID 17623009, 7633595, 2155225, 3039534)Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


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.


7-Hydroxy-6-methyl-8-ribityl lumazine, also known as masuda's compound V or RL-6-me-7-OH, belongs to the class of organic compounds known as pteridines and derivatives. These are polycyclic aromatic compounds containing a pteridine moiety, which consists of a pyrimidine fused to a pyrazine ring to form pyrimido(4,5-b)pyrazine. 7-Hydroxy-6-methyl-8-ribityl lumazine is slightly soluble (in water) and a very weakly acidic compound (based on its pKa). In humans, 7-hydroxy-6-methyl-8-ribityl lumazine is involved in the riboflavin metabolism pathway. 7-Hydroxy-6-methyl-8-ribityl lumazine is an intermediate in Riboflavin metabolism. it is converted from 6,7-Dimethyl-8-(1-D-ribityl)lumazine.


Aldosterone

Aldosterone is a steroid hormone produced by the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood. Specifically it regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. It is synthesized from cholesterol by aldosterone synthase, which is absent in other sections of the adrenal gland. It is the sole endogenous member of the class of mineralocorticoids. Aldosterone increases the permeability of the apical (luminal) membrane of the kidney's collecting ducts to potassium and sodium and activates their basolateral Na+/K+ pumps, stimulating ATP hydrolysis, reabsorbing sodium (Na+) ions and water into the blood, and excreting potassium (K+) ions into the urine.


selenomethionine

Selenomethionine is an amino acid containing selenium that cannot be synthesized by higher animals, but can be obtained from plant material. Selenomethionine is the major seleno-compound in cereal grains (wheat grain, maize and rice), soybeans and enriched yeast. Seleno-compounds present in plants may have a profound effect upon the health of animals and human subjects. It is now known that the total Se content cannot be used as an indication of its efficacy, but knowledge of individual selenocompounds is necessary to fully assess the significance. Thus, speciation of the seleno-compounds has moved to the forefront. Since animals and man are dependent upon plants for their nutritional requirements, this makes the types of seleno-compounds in plants even more critical. Se enters the food chain through incorporation into plant proteins, mostly as selenocysteine and selenomethionine at normal Se levels. There are two possible pathways for the catabolism of selenomethionine. One is the transsulfuration pathway via selenocystathionine to produce selenocysteine, which in turn is degraded to H2Se by the enzyme b-lyase. The other pathway is the transamination-decarboxylation pathway. It was estimated that 90% of methionine is metabolized through this pathway and thus could be also the major route for selenomethionine catabolism. (PMID: 14748935, Br J Nutr. 2004 Jan;91(1):11-28.).


4-(2 Amino-3-hydroxyphenyl)-2,4-dioxobutanoate is found in the tryptophan metabolic pathway and is an intermediate in tryptophan degradation [Kegg: C05645]. More specifically it is an intermediate in the conversion of 3-hydroxy-L-kynurenine to xanthurenate. The conversion is catalyzed by kynurenine aminotransferase (EC 2.6.1.7).


11-epi-PGF2alpha is an intermediate in Arachidonic acid metabolism. 11-epi-PGF2alpha is converted from (5Z,13E)-(15S)-9alpha,15-Dihydroxy-11-oxoprosta-5,13-dienoate via the enzyme prostaglandin-F synthase (EC 1.1.1.188).Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


coproporphyrin III

Coproporphyrin III is a porphyrin metabolite arising from heme synthesis. Porphyrins are pigments found in both animal and plant life. Coproporphyrin III is a tetrapyrrole dead-end product from the spontaneous oxidation of the methylene bridges of coproporphynogen, arising from heme synthesis and secreted in feces and urine. Increased levels of coproporphyrins can indicate congenital erythropoietic porphyria or sideroblastic anaemia. Porphyria is a pathological state characterised by abnormalities of porphyrin metabolism and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. A large number of factors are capable of increasing porphyrin excretion, owing to different and multiple causes and etiologies: 1) the main site of the chronic hepatic porphyria disease process concentrates on the liver, 2) a functional and morphologic liver injury is almost regularly associated with this chronic porphyria, 3) the toxic form due to occupational and environmental exposure takes mainly a subclinical course. Hepatic factors includes disturbance in coproporphyrinogen metabolism, which results from inhibition of coproporphyrinogen oxidase as well as from the rapid loss from, and diminished utilization of coproporphyrinogen in the hepatocytes, which may also explain why coproporphyrin, its autoxidation product, predominates physiologically in the urine; decreased biliary excretion of coproporphyrin leading to a compensatory urinary excretion, so that the coproporphyrin ring isomer ratio (1:III) becomes a sensitive index for impaired liver function and intrahepatic cholestasis; and disturbed activity of hepatic uroporphyrinogen decarboxylase. In itself, secondary coproporphyrinuria is not associated with porphyria symptoms of a hepatologic-gastroenterologic, neurologic, or dermatologic order, even though coproporphyrinuria can occur with such symptoms. (PMID: 3327428).


3,4-dihydroxymandelic acid

3,4-Dihydroxymandelic acid is is a minor metabolite of norepinephrine in humans (PMID 12649306). Patients with neuroblastoma experience elevated levels of 3,4-Dihydroxymandelic acid and other Catecholamines metabolites, and their presence in urine is a good indicator for diagnosis and follow-up (PMID 8193481).


Prostaglandin G2 (PGG2) is synthesized from arachidonic acid on a cyclooxygenase (COX) metabolic pathway as a primary step; the COX biosynthesis of prostaglandin (PG) begins with the highly specific oxygenation of arachidonic acid in the 11R configuration and ends with a 15S oxygenation to form PGG2. The COX site activity that catalyzes the conversion of arachidonic acid to PGG2 is the target for nonsteroidal antiinflammatory drugs (NSAIDs). The peroxidase site activity catalyzes the two-electron reduction of the hydroperoxide bond of PGG2 to yield the corresponding alcohol prostaglandin H2 (PGH2). The formation of a phenoxyl radical on Tyr385 couples the activities of the two sites. The Tyr385 radical is produced via oxidation by compound I, an oxoferryl porphyrin -cation radical, which is generated by reaction of the hemin resting state with PGG2 or other hydroperoxides. The tyrosyl radical homolytically abstracts the 13proS hydrogen atom of arachidonic acid which initiates a radical cascade that ends with the stereoselective formation of PGG2. PGG2 then migrates from the cyclooxygenase (COX) site to the peroxidase (POX) site where it reacts with the hemin group to generate PGH2 and compound I. The heterolytic oxygen-oxygen bond cleavage is assisted by the conserved distal residues His207 and Gln203, mutation of which has been shown to severely impair enzyme activity. Compound I, upon reaction with Tyr385, gives compound II, which in turn is reduced to the hemin resting state by one-electron oxidation of reducing cosubstrates or undergoes reactions that result in enzyme self-inactivation. Prostaglandin endoperoxide H synthase (PGHS) 1 is a bifunctional membrane enzyme of the endoplasmic reticulum that converts arachidonic acid into prostaglandin H2 (PGH2), the precursor of all prostaglandins, thromboxanes, and prostacyclins. These lipid mediators are intricately involved in normal physiology, namely, in mitogenesis, fever generation, pain response, lymphocyte chemotaxis, fertility, and contradictory stimuli such as vasoconstriction and vasodilatation, as well as platelet aggregation and quiescence. PGHS is implicated in numerous pathologies, including inflammation, cancers of the colon, lung, and breast, Alzheimer's disease, Parkinson's disease, and numerous cardiovascular diseases including atherosclerosis, thrombosis, myocardial infarction, and stroke. (PMID: 14594816, 16552393, 16411757). Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


3-Oxohexanoyl-CoA is an intermediate in Fatty acid elongation in mitochondria. 3-Oxohexanoyl-CoA is the 3rd to last step in the synthesis of Hexanoyl-CoA and is converted from Butanoyl-CoA via the enzyme acetyl-CoA acyltransferase 2 (EC 2.3.1.16). It is then converted to (S)-Hydroxyhexanoyl-CoA via the 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35).

3-ketohexanoyl coa.
3-ketohexanoyl coenzyme a.
3-oxohexanoyl-coa
3-oxohexanoyl-coenzyme a
Ketohexanoyl-coa
Ketohexanoyl-coenzyme a


5,6,7,8-tetrahydrofolyl-L-glutamic acid

Tetrahydrofolyl-[Glu](n) is involved in the folate biosynthesis pathway. Tetrahydrofolyl-[Glu](n) can be reversibly converted into Tetrahydrofolyl-[Glu](2) by folylpolyglutamate synthase [EC:6.3.2.17]. Tetrahydrofolyl-[Glu](n) can be irreversibly converted into tetrahydrofolate by gamma-glutamyl hydrolase [EC:3.4.19.9]. Sample structure image shows the case when n=3.


(S)-3-Hydroxydodecanoyl-CoA, also known as (S)-3-hydroxylauroyl-coa, belongs to the class of organic compounds known as (s)-3-hydroxyacyl coas. These are organic compounds containing a (S)-3-hydroxyl acylated coenzyme A derivative (S)-3-Hydroxydodecanoyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa) (S)-3-Hydroxydodecanoyl-CoA has been primarily detected in urine. Within the cell, (S)-3-hydroxydodecanoyl-CoA is primarily located in the cytoplasm (S)-3-Hydroxydodecanoyl-CoA exists in all living organisms, ranging from bacteria to humans. In humans, (S)-3-hydroxydodecanoyl-CoA is involved in the fatty acid metabolism pathway (S)-3-Hydroxydodecanoyl-CoA is also involved in several metabolic disorders, some of which include the fatty acid elongation in mitochondria pathway, long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency (lchad), short chain acyl CoA dehydrogenase deficiency (scad deficiency), and the mitochondrial Beta-oxidation OF medium chain saturated fatty acids pathway. (S)-3-Hydroxydodecanoyl-CoA is a human metabolite involved in the fatty acid elongation in mitochondria pathway. The enzyme long-chain-3-hydroxyacyl-CoA dehydrogenase catalyzes the conversion of 3-Oxododecanoyl-CoA to (S)-3-Hydroxydodecanoyl-CoA.

(s)-3-hydroxydodecanoyl-coenzyme a
(s)-3-hydroxylauroyl-coa
(s)-3-hydroxylauroyl-coenzyme a


2-Hydroxy-3-(4-hydroxyphenyl)propenoic acid is an intermediate in tyrosine metabolism. It is reversibly converted from 4-hydroxyphenylpyruvate via phenylpyruvate tautomerase. 2-Hydroxy-3-(4-hydroxyphenyl)propenoic acid is typically a terminal product of tyrosine metabolism.


(2E)-Tetradecenoyl-CoA is an intermediate in fatty acid metabolism, the substrate of the enzymes acyl-CoA oxidase and Oxidoreductases [EC 1.3.3.6-1.3.99.-] and enzymes acyl-CoA dehydrogenase, long-chain-acyl-CoA dehydrogenase [EC 1.3.99.3-1.3.99.13]; (2E)-Tetradecenoyl-CoA is an intermediate in fatty acid elongation in mitochondria, being the substrate of the enzyme trans-2-enoyl-CoA reductase (NADPH) [EC 1.3.1.38]. (KEGG).


Caffeine

Caffeine is the most widely consumed psychostimulant drug in the world and is mostly consumed in the form of coffee. Whether caffeine and/or coffee consumption contributes to the development of cardiovascular disease (CVD), the single leading cause of death in the US, is unclear. The literature indicates a strong relationship between boiled, unfiltered coffee consumption and elevated cholesterol levels; however, there is a critical gap in the literature regarding the effects of coffee or caffeine consumption on fibrinogen or CRP, which is an independent predictor of CVD risk. Available studies are limited by small samples sizes, the inclusion of only men (or few women), and unrepresented age or ethnic groups. There is a critical need for controlled laboratory and epidemiological studies that include fibrinogen and CRP markers of CVD risk before conclusions can be drawn regarding the health effects of caffeine and/or coffee in a normal, healthy population of men and women (PMID: 16856769 ). The relationship between caffeine consumption and various illnesses such as cardiovascular disease and cancer remains equivocal. Prudence might dictate that pregnant women and chronically ill individuals exercise restraint in their use of caffeine, although research suggests relatively low or nonexistent levels of risk associated with moderate caffeine consumption (PMID: 7844249). There is extensive evidence that caffeine at dietary doses increases blood pressure (BP). However, concern that the drug may contribute to cardiovascular disease appears to have been dampened by (1) the belief that habitual use leads to the development of tolerance, and (2) confusion regarding relevant epidemiologic findings. When considered comprehensively, findings from experimental and epidemiologic studies converge to show that BP remains reactive to the pressor effects of caffeine in the diet. Overall, the impact of dietary caffeine on population BP levels is likely to be modest, probably in the region of 4/2 mm Hg. At these levels, however, population studies of BP indicate that caffeine use could account for premature deaths in the region of 14% for coronary heart disease and 20% for stroke (PMID: 14747639). Caffeine is a purine alkaloid that occurs naturally in coffee beans. At intake levels associated with coffee consumption, caffeine appears to exert most of its biological effects through the antagonism of the A1 and A2A subtypes of the adenosine receptor. Adenosine is an endogenous neuromodulator with mostly inhibitory effects, and adenosine antagonism by caffeine results in effects that are generally stimulatory. Some physiological effects associated with caffeine administration include central nervous system stimulation, acute elevation of blood pressure, increased metabolic rate, and diuresis. Caffeine is rapidly and almost completely absorbed in the stomach and small intestine and distributed to all tissues, including the brain. Caffeine metabolism occurs primarily in the liver, where the activity of the cytochrome P450 isoform CYP1A2 accounts for almost 95% of the primary metabolism of caffeine. CYP1A2-catalyzed 3-demethylation of caffeine results in the formation of 1,7-dimethylxanthine (paraxanthine). Paraxanthine may be demethylated by CYP1A2 to form 1-methylxanthine, which may be oxidized to 1-methyluric acid by xanthine oxidase. Paraxanthine may also be hydroxylated by CYP2A6 to form 1,7-dimethyluric acid, or acetylated by N-acetyltransferase 2 (NAT2) to form 5-acetylamino-6-formylamino-3-methyluracil, an unstable compound that may be deformylated nonenzymatically to form 5-acetylamino-6-amino-3-methyluracil. Caffeine concentrations in coffee beverages can be quite variable. A standard cup of coffee is often assumed to provide 100 mg of caffeine, but a recent analysis of 14 different specialty coffees purchased at coffee shops in the US found that the amount of caffeine in 8 oz (=240 ml) of brewed coffee ranged from 72 to 130 mg. Caffeine in espresso coffees ranged from 58 to 76 mg in a single shot (PMID: 16507475). Caffeine is a member of the methylxanthine family of drugs, and is the most widely consumed behaviourally active substance in the western world. A number of in vitro and in vivo studies have demonstrated that caffeine modulates both innate and adaptive immune responses. For instance, studies indicate that caffeine and its major metabolite paraxanthine suppress neutrophil and monocyte chemotaxis, and also suppress production of the pro-inflammatory cytokine tumour necrosis factor (TNF) alpha from human blood. Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th1 (interleukin [IL]-2 and interferon [IFN]-gamma), Th2 (IL-4, IL-5), and Th3 (IL-10) cytokines. Studies also indicate that caffeine suppresses antibody production. The evidence suggests that at least some of the immunomodulatory actions of caffeine are mediated via inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and consequential increase in intracellular cAMP concentrations. Overall, these studies indicate that caffeine, like other members of the methylxanthine family, is largely anti-inflammatory in nature, and based on the pharmacokinetics of caffeine, many of its immunomodulatory effects occur at concentrations that are relevant to normal human consumption (PMID: 16540173).


D-ribosylnicotinic acid

Nicotinate D-ribonucleoside is involved in the nicotinate and nicotinamide metabolism pathways. Nicotinate D-ribonucleoside can be reversibly converted to nicotinate and nicotinate D-ribonucleoside by purine-nucleoside phosphorylase [EC:2.4.2.1] and 5'-nucleotidase [EC:3.1.3.5], respectively.

D-ribosylnicotinate
Nicotinate riboside
Nicotinic acid ribose
Nicotinic acid riboside
Ribosylnicotinate
Nicotinate d-ribonucleoside
Nicotinic acid d-ribonucleoside


2-Hexaprenyl-6-methoxy-1,4-benzoquinone is involved in the ubiquinone biosynthesis pathway. 2-Hexaprenyl-6-methoxy-1,4-benzoquinone is created from 2-Hexaprenyl-6-methoxyphenol by ubiquinone biosynthesis monooxygenase Coq6 [EC:1.14.13.-]. 2-Hexaprenyl-6-methoxy-1,4-benzoquinone is then converted into 2-Hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinone by ubiquinone biosynthesis methyltransferase [EC:2.1.1.-].


methacrylyl-CoA

Methacrylyl-CoA is a metabolite in the valine, leucine and isoleucine degradation pathway and highly reacts with free thiol compounds (PMID 14684172; KEGG). Cirrhosis results in a significant decrease in 3--hydroxyisobutyryl-CoA hydrolase activity, a key enzyme in the valine catabolic pathway that plays an important role in the catabolism of a potentially toxic compound, methacrylyl-CoA, formed as an intermediate in the catabolism of valine and isobutyrate. (PMID: 8938168).

2-methylprop-2-enoyl-coa
2-methylprop-2-enoyl-coenzyme a
Methacrylyl coa
Methacrylyl coenzyme a
Methacrylyl-coenzyme a
Methylacrylyl-coa
Methylacrylyl-coenzyme a
S-(2-methyl-2-propenoate
S-(2-methyl-2-propenoate) coa
S-(2-methyl-2-propenoate) coenzyme a
S-(2-methyl-2-propenoic acid


3-Hydroxypropionyl-CoA is an intermediate in b-Alanine (beta-alanine) metabolism. It can be produced from 3-hydroxypropanoic acid via the enzyme 3-hydroxyisobutyryl-Coenzyme A hydrolase (EC:3.1.2.4) or it can be generated from acrylyl CoA via the enzyme enoyl-CoA hydratase (EC:4.2.1.17). Acrylyl CoA is derived from propionyl CoA.

3-hydroxypropanoyl coenzymea
3-hydroxypropanoyl-coa
3-hydroxypropanoyl-coenzyme a
3-hydroxypropionyl coenzyme a


Diamorphine

Heroin, also known as diacetylmorphine or diagesil, belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic. Heroin is a drug which is used in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain. Heroin exists as a solid and is considered to be practically insoluble (in water) and relatively neutral. Heroin can be biosynthesized from morphine. Heroin is a potentially toxic compound.

(5a,6a)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester)

(5alpha,6alpha)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester)

(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetic acid (ester)


L-4-hydroxyglutamic semialdehyde

L-4-Hydroxyglutamate semialdehyde is an intermediate in Arginine and proline metabolism. L-4-Hydroxyglutamate semialdehyde is the 4th to last step in the synthesis of Glyoxylate and is converted from L-erythro-4-Hydroxyglutamate via the enzyme 1-pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12). It is then converted to L-1-Pyrroline-3-hydroxy-5-carboxylate via enzymtic reaction.


Methylselenocysteine

Se-Methylselenocysteine (SeMSC) is a naturally occurring seleno-amino acid that is synthesized by plants such as garlic, astragalus, onions and broccoli. Unlike selenomethionine, which is incorporated into proteins in place of methionine, SeMSC is not incorporated into any proteins, thereby being fully available for the synthesis of selenium-containing enzymes such as glutathione peroxidase.

3-(methylseleno)-l-alanine
Methylselenocysteine
Se-methyl-l-selenocysteine
Selenium-methylselenocystine
L-methylselenocysteine
Methyl-l-selenocysteine
Se-methyl-seleno-l-cysteine
Se-methyl-selenocysteine
Se-methylselenocysteine
Selenium methyl cysteine
Selenohomocysteine
Selenomethylselenocysteine
(2r)-2-amino-3-methylselanylpropanoate


12-dehydro-leukotriene B4

12-Keto-leukotriene B4 is formed when leukotriene B4 (LTB4) is metabolized by beta-oxidation. LTB4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. (PMID: 8632343, 9667737)Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


Produced by the seminal vesicles, prostaglandins are a group of lipid compounds that are derived enzymatically from fatty acids. Technically hormones, the prostanoid class of fatty acid derivatives is a subclass of eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signaling pathways. Prostaglandin A is a cyclopentenone and is an endogenous metabolite derived from arachidonic acid. It exhibits potent cellular anti-proliferative activity in vivo and in vitro. Excess PGA2 causes an accumulation in both S and G2/M, and a marked decrease in G1. There is also an increase in DNA content preceeding the G0/G1 peak (indicative of apoptotic body formation) mediated by changes in expression levels of Bax and Bcl-2.


(S)-methylmalonaldehydic acid

Methylmalonic semialdehyde is a metabolite in valine catabolism, inositol metabolism and propanoate metabolism. Methylmalonate-semialdehyde dehydrogenase (MMSDH) catalyses the NAD+ and coenzyme A-dependent conversion of methylmalonate semialdehyde to propionyl-CoA in the distal region of the L-valine catabolic pathway. MMSDH is located within the mitochondria; direct enzymatic assay of MMSDH is difficult since the substrate, methylmalonate semialdehyde, is both commercially unavailable and notoriously unstable as a b-keto acid. (PMID: 10947204).

(2s)-2-methyl-3-oxopropanoate
(2s)-2-methyl-3-oxopropanoic acid
(s)-methylmalonate semialdehyde
(s)-methylmalonic acid semialdehyde


(5-hydroxyindol-3-yl)acetic acid

5-hydroxyindoleacetic acid (5HIAA) is a breakdown product of serotonin that is excreted in the urine. Serotonin is a hormone found at high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors. (NCI).


17alpha,21-Dihydroxypregnenolone is an intermediate in the human fetus at midpregnancy that is converted into cortisol (PMID: 4231965). It has also been found as an intermediate in alternative pathways in human adrenal steroidogenesis that take place under in vitro conditions. In normal adrenal slices from patients with hypernephroid kidney carcinomas these pathways bypass cholesterol, pregnenolone, and progesterone, and proceed to 21-hydroxypregnenolone (PMID: 6247575). 17alpha,21-Dihydroxypregnenolone is an intermediate in C21-Steroid hormone metabolism. 17alpha,21-Dihydroxypregnenolone is the 5th to last step in the synthesis of Cortol and is converted from 17alpha-Hydroxypregnenolone via the enzyme cytochrome P450 (EC 1.14.99.10). It is then converted to 11beta,17alpha,21-Trihydroxypregnenolone via the enzyme cytochrome P450 (EC 1.14.15.4).


N1-Methyl-4-pyridone-5-carboxamide (4PY ) is a normal human metabolite (one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation). 4PY concentration in serum is elevated in non-dialyzed chronic renal failure (CRF) patients when compared with controls. (PMID 12694300).


Iodotyrosine is an iodated derivative of L-tyrosine. This is an early precursor to L-thyroxine, one of the primary thyroid hormones. In the thyroid gland, iodide is trapped, transported, and concentrated in the follicular lumen for thyroid hormone synthesis. Before trapped iodide can react with tyrosine residues, it must be oxidized by thyroid peroxidase. Iodotyrosine is made from tyrosine via thyroid peroxidase and then further iodinated by this enzyme to make the di-iodo and tri-iodo variants. Two molecules of di-iodotyrosine combine to form T4, and one molecule of mono-iodotyrosine combines with one molecule of di-iodotyrosine to form T3.


3,4-Dihydroxymandelaldehyde is the monoamine oxidase (MAO) aldehyde metabolite of both norepinephrine and epinephrine. 3,4- dihydroxymandelaldehyde generates a free radical and activates mitochondrial permeability transition, a mechanism implicated in neuron death. There is an increasing body of evidence suggesting that these compounds are neurotoxic, and it has been recently hypothesized that neurodegenerative disorders may be associated with increased levels of this biogenic aldehyde. It is possible to speculate that reduced detoxification of 3,4- dihydroxymandelaldehyde from impaired or deficient aldehyde dehydrogenase function may be a contributing factor in the suggested neurotoxicity of these compounds. Aldehyde dehydrogenases are a group of NAD(P)+ -dependent enzymes that catalyze the oxidation of aldehydes, such as those derived from catecholamines, to their corresponding carboxylic acids. To date, 19 aldehyde dehydrogenase genes have been identified in the human genome. Mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases. Several pharmaceutical agents and environmental toxins are also known to disrupt or inhibit aldehyde dehydrogenase function. (PMID: 17379813, 14697885, 11164826).


5-Methylthioribose 1-phosphate is an intermediate in methionine biosynthesis. It is converted from 5'-Deoxy-5'-methylthioadenosine by 5'-Deoxy-5'-methylthioadenosine phosphorylase. Then it is converted to methionine (PMID 2153115). In the methionine salvage pathway 5-methylthioribose 1-phosphate isomerase (M1Pi) catalyzes the conversion of 5-methylthioribose 1-phosphate (MTR-1-P) to 5-methylthioribulose 1-phosphate (MTRu-1-P).


3-Oxododecanoyl-CoA, also known as 3-oxolauroyl-coa, belongs to the class of organic compounds known as 3-oxo-acyl coas. These are organic compounds containing a 3-oxo acylated coenzyme A derivative. 3-Oxododecanoyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). 3-Oxododecanoyl-CoA has been primarily detected in urine. Within the cell, 3-oxododecanoyl-CoA is primarily located in the cytoplasm. 3-Oxododecanoyl-CoA exists in all living organisms, ranging from bacteria to humans. 3-Oxododecanoyl-CoA participates in a number of enzymatic reactions. In particular, 3-Oxododecanoyl-CoA can be biosynthesized from (S)-3-hydroxydodecanoyl-CoA through its interaction with the enzyme enoyl-CoA hydratase. In addition, 3-Oxododecanoyl-CoA can be converted into acetyl-CoA and tetradecanoyl-CoA; which is catalyzed by the enzyme acetyl-CoA C-acyltransferase. In humans, 3-oxododecanoyl-CoA is involved in the fatty acid metabolism pathway. 3-Oxododecanoyl-CoA is also involved in several metabolic disorders, some of which include the glutaric aciduria type I pathway, long chain acyl-CoA dehydrogenase deficiency (lcad), short chain acyl CoA dehydrogenase deficiency (scad deficiency), and carnitine palmitoyl transferase deficiency (I). 3-Oxododecanoyl-CoA is a human metabolite involved in the fatty acid elongation in mitochondria pathway. The enzyme acetyl-CoA C-acyltransferase catalyzes the formation of this metabolite from Acetyl-CoA.


chloroacetaldehyde

Being bifunctional, chloroacetaldehyde is a versatile precursor to many heterocyclic compounds. It condenses with thiourea derivatives to give aminothiazoles. This reaction was once important as a precursor to sulfathiazole, one of the first sulfa drugs. Chloroacetaldehyde is the organic compound with the formula ClCH2CHO. Like some related compounds, it is highly electrophilic reagent and a potentially dangerous alkylating agent. The compound is not normally encountered in the anhydrous form, but rather as the hydrate (acetal), ClCH2CH(OH)2. Chloroacetaldehyde is a useful intermediate in the synthesis, e.g. of 2-aminothiazole or many pharmaceutical compounds. Another use is to facilitate bark removal from tree trunks.


Tetracycline

Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.


phenylsulfate

Phenol sulphate, also known as phenylsulfate or aryl sulphate, belongs to the class of organic compounds known as phenylsulfates. Phenylsulfates are compounds containing a sulfuric acid group conjugated to a phenyl group. Phenol sulphate is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). Phenol sulphate has been detected in multiple biofluids, such as feces and urine. Within the cell, phenol sulphate is primarily located in the cytoplasm. Phenol sulphate exists in all living organisms, ranging from bacteria to humans. In humans, phenol sulphate is involved in the sulfate/sulfite metabolism pathway. Phenol sulphate is also involved in the metabolic disorder called sulfite oxidase deficiency. Phenol sulphate belongs to the family of Substituted Benzenes. These are aromatic compounds containing a benzene substituted at one or more positions.

Phenyl hydrogen sulfate
Phenylsulfate
Aryl sulfate
Sulfuric acid, monophenyl ester
Phenyl hydrogen sulphate
Phenylsulphate
Aryl sulphate
Phenol sulfate
Phenol sulfuric acid
Phenol sulphuric acid
Phenylsulfuric acid
Phenylsulphuric acid


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).


3-Methoxy-4-hydroxyphenylglycolaldehyde is the monoamine oxidase (MAO) aldehyde metabolite of metanephrine. Metanephrine is an O-methylated metabolite formed by catechol-O-methyltransferase (COMT) from epinephrine. Catecholamines play an important role in platelet activation and aggregation, epinephrine being the most potent one. Catecholamines are substantially increased during stress, exercise or smoking and could result in clinically important platelet activation if their action was not rapidly regulated. The inhibitory effects of methoxy phenolic derivatives on epinephrine-induced platelet aggregation may possibly be attributed to their free radical scavenging properties. There is substantial evidence to conclude that an internal rapid autoregulation of epinephrine-induced platelet aggregation, caused by its metabolic degradation products, takes place in vivo. (PMID: 11958479, 9706478).


Cocaine

An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [PubChem]

[1r-(exo,exo)]-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid, methyl ester

2-methyl-3b-hydroxy-1alphah,5alphah-tropane-2b-carboxylic acid benzoic acid (ester)

2-methyl-3beta-hydroxy-1alphah,5alphah-tropane-2beta-carboxylic acid benzoic acid (ester)

2-methyl-3β-hydroxy-1alphah,5alphah-tropane-2β-carboxylic acid benzoic acid (ester)


11beta-Hydroxyandrost-4-ene-3,17-dione is an intermediate in adrenosterone production. 11beta-Hydroxyandrost-4-ene-3,17-dione is produced from androst-4-ene-3,17-dione, a reaction catalyzed by the enzyme cytochrome P450 B [EC:1.14.15.4]. 11beta-Hydroxyandrost-4-ene-3,17-dione is then converted into adrenosterone by the enzyme 11beta-hydroxysteroid dehydrogenase [EC:1.1.1.146].


Estriol

Estriol is a metabolite of estrone metabolized via 16alpha-hydroxyestrone through the enzyme 16alpha-hydroxysteroid dehydrogenase (EC 1.1.1.147) or to 2- or 4-hydroxyestrone (catechol estrogens) by the action of catecho-O-methyltransferase (EC 2.1.1.6). The latter metabolites can be formed in the brain and may compete with receptors for catecholamines. Metabolites are conjugated with sulfate or glucuronide before excretion by the kidney. During pregnancy, estriol constitutes 60-70% of the total estrogens, increasing to 300-500-fold in relation to non-pregnant women. The late term human fetus produces relatively large amounts of 16 alphahydroxy DHEA, which serves the mother as a precursor of estriol. It has been shown that 90% of the precursors for the formation of estriol are of fetal origin. If abnormal maternal serum screening results, specifically low levels of unconjugated estriol in the second trimester are detected, a diagnosis of Smith-Lemli-Opitz syndrome (SLOS),or RSH is suspected. SLOS is an autosomal recessive disorder caused by mutations of the gene encoding 7-dehydrocholesterol reductase (EC 1.3.1.21, DHCR7). (PMID: 16202579, 16112271, 16097001).


3,4-Dihydroxyphenylacetaldehyde (DOPAL) is a metabolite of the monoamine oxidase-catalyzed oxidative deamination of dopamine. Aldehydes are highly reactive molecules formed during the biotransformation of numerous endogenous and exogenous compounds, including biogenic amines. DOPAL generates a free radical and activates mitochondrial permeability transition, a mechanism implicated in neuron death. There is an increasing body of evidence suggesting that these compounds are neurotoxic, and it has been recently hypothesized that neurodegenerative disorders may be associated with increased levels of this biogenic aldehyde. It is possible to speculate that reduced detoxification of 3,4- dihydroxymandelaldehyde from impaired or deficient aldehyde dehydrogenase function may be a contributing factor in the suggested neurotoxicity of these compounds. Aldehyde dehydrogenases are a group of NAD(P)+ -dependent enzymes that catalyze the oxidation of aldehydes, such as those derived from catecholamines, to their corresponding carboxylic acids. To date, 19 aldehyde dehydrogenase genes have been identified in the human genome. Mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases. Several pharmaceutical agents and environmental toxins (i.e.: 4-hydroxy-2-nonenal) are also known to disrupt or inhibit aldehyde dehydrogenase function. (PMID: 17379813, 14697885, 11164826, 16956664.


2-Methyl-3-hydroxy-5-formylpyridine-4-carboxylate is an intermediate in vitamin B6 metabolism(KEGG ID C06050). It is the 4th to last step in the synthesis of succinate semialdehyde, which is an intermediate in butanoate metabolism. 2-Methyl-3-hydroxy-5-formylpyridine-4-carboxylate is converted from 4-pyridoxate and is then converted to 3-hydroxy-2-methylpyridine-4,5-dicarboxylate.


21-hydroxypregnenolone is an essential intermediate in corticosterone synthesis. The hydrolysis of 21-hydroxypregnenolone of fetal origin by steryl-sulfatase (SOS, EC 3.1.6.2), may be important in the biosynthesis of deoxycorticosterone, which is present in the plasma of pregnant women in high concentration. 21-hydroxypregnenolone has been identified in follicular fluid from follicles of women. Pregnenolone is transformed to 21-hydroxypregnenolone by human adrenal microsomal preparations, suggesting the involvement of alternative paths via 17a,21-dihydroxypregnenolone in human. (PMID 974176, 3347051, 3495701, 7382480, 6247575).


3alpha,7alpha-Dihydroxy-5beta-cholestane is an intermediate in bile acid synthesis. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues. (PMID: 11316487, 16037564, 12576301, 11907135).


melibiose

Melibiose is disaccharide consisting of one galactose and one glucose moiety in an alpha (1-6) glycosidic linkage. This sugar is produced and metabolized only by enteric and lactic acid bacteria and other microbes. It is not an endogenous metabolite but may be obtained from the consumption of partially fermented molasses, brown sugar or honey. Antibodies to melibiose will appear in individuals affected by Chagas' disease (Trypanosoma cruzi infection). Melibiose is not metabolized by humans, but can be broken down by gut microflora, such as E. coli. In fact, E. coli is able to utilize melibiose as a sole source of carbon. Melibiose is first imported by the melibiose permease, MelB and then converted to β-D-glucose and β-D-galactose by the α-galactosidase encoded by melA. Because of its poor digestability Melibiose (along with rhamnose) can be used together for noninvasive intestinal mucosa barrier testing. This test can be used to assess malabsorption or impairment of intestinal permeability. Recent studies with dietary melibiose have shown that can strongly affected the Th cell responses to an ingested antigen. It has been suggested that melibiose could be used to enhance the induction of oral tolerance. (PMID 17986780).


galactose

D-Galactose is an aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. D-Galactose is an energy-providing nutrient and also a necessary basic substrate for the biosynthesis of many macromolecules in the body. Metabolic pathways for D-Galactose are important not only for the provision of these pathways but also for the prevention of D-Galactose and D-Galactose metabolite accumulation. The main source of D-Galactose is lactose in the milk of mammals, but it can also be found in some fruits and vegetables. Utilization of D-Galactose in all living cells is initiated by the phosphorylation of the hexose by the enzyme galactokinase (E.C. 2.7.1.6) (GALK) to form D-Galactose-1-phosphate. In the presence of D-Galactose-1-phosphate uridyltransferase (E.C. 2.7.7.12) (GALT) D-Galactose-1-phosphate is exchanged with glucose-1-phosphate in UDP-glucose to form UDP-galactose. Glucose-1-phosphate will then enter the glycolytic pathway for energy production. Deficiency of the enzyme GALT in galactosemic patients leads to the accumulation of D-Galactose-1-phosphate. Classic galactosemia-a term that denotes the presence of D-Galactose in the blood is the rare inborn error of D-Galactose metabolism, diagnosed by the deficiency of the second enzyme of the D-Galactose assimilation pathway, GALT, which, in turn, is caused by mutations at the GALT gene. (PMID: 15256214, 11020650, 10408771).

(+)-galactose
5abp
8abp
D-(+)-galactose
D-galactose
D-hexose
Gal
Gla
Glc
Galactose
Galactose (nf)
Hexose
Alpha d-galactose
Alpha-d-galactopyranose
Alpha-d-galactose
Alpha-d-gal
Gal-alpha
A d-galactose
α d-galactose
A-d-gal
α-d-gal
Gal-a
Gal-α


glycogen

Glycogen is a highly-branched polymer of about 30,000 glucose residues and has a molecular weight between 106 and 107 daltons (4.8 million approx.). Most of Glc units are linked by alpha-1,4 glycosidic bonds, approximately 1 in 12 Glc residues also makes -1,6 glycosidic bond with a second Glc which results in the creation of a branch. Glycogen only has one reducing end and a large number of non-reducing ends with a free hydroxyl group at carbon 4. The glycogen granules contain both glycogen and the enzymes of glycogen synthesis (glycogenesis) and degradation (glycogenolysis). The enzymes are nested between the outer branches of the glycogen molecules and act on the non-reducing ends. Therefore, the many non-reducing end-branches of glycogen facilitate its rapid synthesis and breakdown. In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but the high insulin level prevents the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia. Glycogen is a polysaccharide that is the principal storage form of glucose (Glc) in animal and human cells. Glycogen is found in the form of granules in the cytosol in many cell types. Hepatocytes (liver cells) have the highest concentration of it - up to 8% of the fresh weight in well fed state, or 100 to 120 g in an adult - giving liver a distinctive, 'starchy taste'. In the muscles, glycogen is found in a much lower concentration (1% of the muscle mass), but the total amount exceeds that in liver. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood cells.

Animal starch
Glycogen
Liver starch
Lyoglycogen
Phytoglycogen


Prostaglandin B2

Prostaglandin B2 (PGB2) is a prostanoid. Prostanoids is a term that collectively describes prostaglandins, prostacyclines and thromboxanes. Prostanoids are a subclass of the lipid mediator group known as eicosanoids. They derive from C-20 polyunsaturated fatty acids, mainly dihomo-gamma-linoleic (20:3n-6), arachidonic (20:4n-6), and eicosapentaenoic (20:5n-3) acids, through the action of cyclooxygenases-1 and -2 (COX-1 and COX-2). The reaction product of COX is the unstable endoperoxide prostaglandin H (PGH) that is further transformed into the individual prostanoids by a series of specific prostanoid synthases. Prostanoids are local-acting mediators formed and inactivated within the same or neighbouring cells prior to their release into circulation as inactive metabolites (15-keto- and 13,14-dihydroketo metabolites). Non-enzymatic peroxidation of arachidonic acid and other fatty acids in vivo can result in prostaglandin-like substances isomeric to the COX-derived prostaglandins that are termed isoprostanes. Prostanoids take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. Their activities are mediated through prostanoid-specific receptors and intracellular signalling pathways, whilst their biosynthesis and action are blocked by nonsteroidal antiinflammatory drugs (NSAID). Isoprostanes are considered to be reliable markers of oxidant stress status and have been linked to inflammation, ischaemia-reperfusion, diabetes, cardiovascular disease, reproductive disorders and diabetes. (PMID: 16986207). Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.


Amylose

Amylose is defined as a linear molecule of (1→4) linked alpha-D-glucopyranosyl units, but it is today well established that some molecules are slightly branched by (1→6)-alpha-linkages. The oldest criteria for linearity consisted in the susceptibility of the molecule to complete hydrolysis by beta-amylase. This enzyme splits the (1→4) bonds from the non-reducing end of a chain releasing beta-maltosyl units, but cannot cleave the (1→6) bonds. When degraded by pure beta-amylase, linear macromolecules are completely converted into maltose, whereas branched chains give also one beta-limit dextrin consisting of the remaining inner core polysaccharide structure with its outer chains recessed. Starches of different botanical origins possess different granular sizes, morphology, polymorphism and enzyme digestibility. These characteristics are related to the chemical structures of the amylopectin and amylose and how they are arranged in the starch granule. (PMID 9730163).


Methyimidazole acetaldehyde is a metabolite of histamine. The metabolites of ethanol and acetaldehyde can successfully compete with methylimidazole acetaldehyde, since the alcohol and histamine metabolic pathways in the body have two enzymes in common, aldehyde dehydrogenase and aldehyde oxidase. (PMID: 10344773).

1-methylimidazole-4-acetaldehyde
Methylimidazoleacetaldehyde
Methylimidazole acetaldehyde


Homovanillin

3 -Methoxy-4-hydroxyphenylacetaldehyde is an intermediary aldehyde of dopamine metabolism, metabolized by the class I human liver alcohol dehydrogenases (ADHs). ADH catalyzes both ethanol and acetaldehyde, and the dopamine intermediates compete for the same site of ADH, a basis for the ethanol-induced in vivo alterations of dopamine metabolism. (PMID 2432930).


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].


2-Oxoarginine is a guanidino compound metabolite of arginine catabolism. 2-Oxoarginine levels are increased in patients with argininemia (OMIM:207800). Argininemia, characterized by arginase deficiency (EC 3.5.3.1, catalyzes the last step of the urea cycle) is an autosomal recessive inborn error of metabolism caused by a defect in the final step in the urea cycle, the hydrolysis of arginine to urea and ornithine. Accumulation of arginine metabolites (such as guanidino compounds) especially 2-oxoarginine, may produce the central nervous system damage in argininemia. (PMID: 3433275, 1588833, 1690873, 819629).


Doconexent

Docosahexaenoic acid (DHA) is an omega-3 essential fatty acid. Chemically, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds with the first double bond located at the third carbon from the omega end. DHA is most often found in fish oil. It is a major fatty acid in sperm and brain phospholipids, especially in the retina. Dietary DHA can reduce the level of blood triglycerides in humans, which may reduce the risk of heart disease (Wikipedia). Docosahexaenoic acid is found to be associated with isovaleric acidemia, which is an inborn error of metabolism.