2,5-Diaminopyrimidine nucleoside triphosphate belongs to the class of organic compounds known as pentose phosphates. These are carbohydrate derivatives containing a pentose substituted by one or more phosphate groups. 2,5-Diaminopyrimidine nucleoside triphosphate is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). 2,5-Diaminopyrimidine nucleoside triphosphate exists in all living organisms, ranging from bacteria to humans. In humans, 2,5-diaminopyrimidine nucleoside triphosphate is involved in pterine biosynthesis pathway. 2,5-Diaminopyrimidine nucleoside triphosphate is also involved in several metabolic disorders, some of which include hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (PTPS), hyperphenylalaninemia due to DHPR-deficiency, sepiapterin reductase deficiency, and hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency. 2,5-Diaminopyrimidine nucleoside triphosphate is involved in folate biosynthesis. 2,5-Diaminopyrimidine nucleoside triphosphate is created from 2,5-Diaminopyrimidine nucleoside triphosphate by GTP cyclohydrolase I [EC:3.5.4.16].


Latrepirdine

Latrepirdine, also known as dimebone or preparation 84, belongs to the class of organic compounds known as n-alkylindoles. N-alkylindoles are compounds containing an indole moiety that carries an alkyl chain at the 1-position. Latrepirdine is considered to be a practically insoluble (in water) and relatively neutral molecule. In humans, latrepirdine is involved in the latrepirdine H1-antihistamine action pathway. Latrepirdine is a tricyclic H1-antihistamine.


Sufentanil

Sufentanil is only found in individuals that have used or taken this drug. It is an opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. [PubChem]Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Sufentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids open calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.


Sulindac

Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA's except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.


Suprofen

Suprofen is only found in individuals that have used or taken this drug. It is an ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. [PubChem]Suprofen binds to the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. The overall result is a reduction in pain and inflammation in the eyes and the prevention of pupil constriction during surgery. Normally trauma to the anterior segment of the eye (especially the iris) increases endogenous prostaglandin synthesis which leads to constriction of the iris sphincter.


taurodeoxycholic acid

Taurodeoxycholic acid is a bile salt formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. 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).

Taurodeoxycholic acid sodium salt hydrate


Telmisartan

Telmisartan is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as telmisartan bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.


Temocaprilat

Temocaprilat, also known as RS 5139, belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond. Temocaprilat is considered to be a practically insoluble (in water) and relatively neutral molecule. In humans, temocaprilat is involved in the temocapril metabolism pathway and the temocapril action pathway.


Argatroban

Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.


Chlorcyclizine

Chlorcyclizine, also known as di-paralene or histachlorazine, belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. Chlorcyclizine is considered to be a practically insoluble (in water) and relatively neutral molecule. In humans, chlorcyclizine is involved in the chlorcyclizine H1-antihistamine action pathway. Chlorcyclizine is a first-generation piperazine H1-antihistamine.


Levocetirizine

Levocetirizine, also known as xazal or xusal, belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. Levocetirizine is considered to be a practically insoluble (in water) and relatively neutral molecule. In humans, levocetirizine is involved in the levocetirizine H1-antihistamine action pathway. Levocetirizine is a second-generation piperazine H1-antihistamine. It has also been labeled as a third-generation antihistamine because it is developed from a second-generation antihistamine (cetirizine).


Pimethixene

Pimethixene, also known as calmixene or BP 400, belongs to the class of organic compounds known as thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom. Pimethixene is considered to be a practically insoluble (in water) and relatively neutral molecule. In humans, pimethixene is involved in the pimethixene H1-antihistamine action pathway. Pimethixene is a thioxanthene H1-antihistamine.


Tetrahydrocorticosterone

Tetrahydrocorticosterone is one of the major urinary metabolites from corticosterone. Premenopausal patients with early breast cancer excrete subnormal amounts of tetrahydrocorticosterone as compared with the normal subjects of corresponding ages. (PMID 1133844).


thiamine(1+) triphosphate

Thiamine triphosphate is the triphosphate ester of thiamine. Thiamine triphosphate (ThTP) was previously considered to be a specific neuroactive form of thiamine. However, it was recently shown that ThTP exists in bacteria, fungi, plants and animals suggesting a much more general cellular role. In particular, it seems to play a role in response to amino acid starvation. In mammals, ThTP is hydrolyzed by a specific thiamine triphosphatase. In Leigh's disease, this compound is present in decreased amounts in the brain due to a metabolic block in its formation.

Thtp
Thiamin triphosphate
Thiamine triphosphate
Thiamin triphosphoric acid


Tioguanine

Thioguanine is only found in individuals that have used or taken this drug. It is an antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem]Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides.


Ticlopidine

Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [PubChem]


Tirofiban

Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide reversible antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation.


Tocainide

Tocainide is only found in individuals that have used or taken this drug. It is an antiarrhythmic agent which exerts a potential- and frequency-dependent block of sodium channels. [PubChem]Tocainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. Tocainide binds preferentially to the inactive state of the sodium channels.The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.


Torasemide

Torasemide (rINN) or torsemide (USAN) is a pyridine-sulfonylurea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex. [Wikipedia]


Valsartan

Valsartan is an angiotensin-receptor blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Valsartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Valsartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.


Venlafaxine

Venlafaxine (brand name: Effexor or Efexor) is an effective antidepressant for many persons; Venlafaxine is a bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It works by blocking the transporter reuptake proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitter in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline) Additionally, in high doses it weakly inhibits the reuptake of dopamine; A comparison of adverse event rates in a fixed dose study comparing venlafaxine 75, 225, and 375 mg/day with placebo revealed a dose dependency for some of the more common adverse events associated with venlafaxine use. The rule for including events was to enumerate those that occurred at an incidence of 5% or more for at least one of the venlafaxine groups and for which the incidence was at least twice the placebo incidence for at least one venlafaxine group. Tests for potential dose relationships for these events (Cochran-Armitage Test, with a criterion of exact 2-sided p-value <= 0.05) suggested a dose-dependency for several adverse events in this list, including chills, hypertension, anorexia, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.[Wyeth Monograph]; Venlafaxine is an effective anti-depressant for many persons; however, it seems to be especially effective for those with treatment resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. Patients suffering with severe long-term depression typically respond better to venlafaxine than other drugs. However, venlafaxine has been reported to be more difficult to discontinue than other antidepressants. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. However, this should not be considered a definitive finding, since responses to psychiatric medications can vary significantly from individual to individual; however, it seems to be especially effective for those with treatment-resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. Patients suffering with severe long term depression typically respond better to venlafaxine than other drugs. However, venlafaxine has been reported to be more difficult to discontinue than other antidepressants. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. However, this should not be considered a definitive finding, since responses to psychiatric medications can vary significantly from individual to individual; Venlafaxine hydrochloride is a prescription antidepressant that belongs to the class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRI). A Black Box Warning has been issued with Venlafaxine and with other SSRI and SNRI anti-depressants advising of risk of suicide. There is an additional risk if a physician misinterprets patient expression of adverse effects such as panic or akithesia. Careful assessment of patient history and comorbid risk factors such as drug abuse are essential in evaluating the safety of Venlafaxine for individual patients. Another risk is Serotonin syndrome. This is a serious effect that can be caused by interactions with other drugs and is potentially fatal. This risk necessitates clear information to patients and proper medical history. Venlafaxine is used primarily for the treatment of depression, generalized anxiety disorder, obsessive compulsive disorder, social anxiety disorder, and panic disorder in adults. It is also used for other general depressive disorders. Although it is not approved for use in children or adolescents, there is a considerable information by Wyeth on cautions if presecribed to this age group. Venlafaxine hydrochloride is a prescription antidepressant first introduced by Wyeth in 1993. It belongs to class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRI). As of August 2006, generic venlafaxine is available in the United States.

Efectin Efexor Effexor Trevilor Venlafaxin Venlafexine Elafax Venlafaxina Venlafaxinum


2-amino-3-carboxymuconic acid semialdehyde is an intermediate metabolite of the tryptophan-niacin catabolic pathway. Current interest in the degradation of tryptophan is mostly due to the role of quinolinate and other metabolites in several neuropathological conditions. Quinolinate is a neurotoxin formed nonenzymatically from 2-amino-3-carboxymuconic semialdehyde in mammalian tissues. 2-Amino-3-carboxymuconic semialdehyde is enzymatically converted to 2-aminomuconate via 2-aminomuconic semialdehyde. (PMID: 10510494, 16267312, 14275129).


Golgi membrane

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


biolink:BiologicalProcess biolink:Occurrent biolink:OntologyClass biolink:BiologicalProcessOrActivity biolink:BiologicalEntity biolink:ThingWithTaxon biolink:NamedThing biolink:PhysicalEssenceOrOccurrent

Gram-negative-bacterium-type cell outer membrane assembly


Phosphatidylcholine

PC(18:3(9Z,12Z,15Z)/18:2(9Z,12Z)) is a phosphatidylcholine (PC or GPCho). It is a glycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. As is the case with diacylglycerols, glycerophosphocholines can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 16, 18 and 20 carbons are the most common. PC(18:3(9Z,12Z,15Z)/18:2(9Z,12Z)), in particular, consists of one chain of a-linolenic acid at the C-1 position and one chain of linoleic acid at the C-2 position. The a-linolenic acid moiety is derived from seed oils, especially canola and soybean oil, while the linoleic acid moiety is derived from seed oils. Phospholipids, are ubiquitous in nature and are key components of the lipid bilayer of cells, as well as being involved in metabolism and signaling.While most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone, the fatty acid distribution at the C-1 and C-2 positions of glycerol within phospholipids is continually in flux, owing to phospholipid degradation and the continuous phospholipid remodeling that occurs while these molecules are in membranes. PCs can be synthesized via three different routes. In one route, choline is activated first by phosphorylation and then by coupling to CDP prior to attachment to phosphatidic acid. PCs can also synthesized by the addition of choline to CDP-activated 1,2-diacylglycerol. A third route to PC synthesis involves the conversion of either PS or PE to PC.


Galactosylceramide

Galactosylceramides (GalCer) are non-acidic monoglycosphingolipids, i.e. a sphingolipid with one carbohydrate moiety attached to a ceramide unit. They are an intermediate in sphingolipid metabolism and is the second to last step in the synthesis of digalactosylceramidesulfate. GalCer is generated from ceramide via the enzyme UDP-galactose ceramide galactosyltransferase [EC:2.4.1.47]. It can be converted to digalactosylceramide via the enzyme glycosyltransferases [EC 2.4.1.-]. Galactosylceramide is the principal glycosphingolipid in brain tissue, hence the trivial name "cerebroside", which was first conferred on it in 1874. Galactosylceramides are found in all nervous tissues, but they can amount to 2% of the dry weight of grey matter and 12% of white matter. They are major constituents of oligodendrocytes. Synthesis of galactosylceramide takes place on the lumenal surface of the endoplasmic reticulum, although it has free access to the cytosolic surface by an energy-independent flip-flop process. GalCer sits in the extracellular leaflet of cell membranes in nanometer sized domains or rafts. The local clustering of GalCer within rafts is thought to facilitate the initial adhesion of certain viruses, including HIV-1 and bacteria to cells through multivalent interactions between receptor proteins and GalCer. A defect in the degradation of cerbrosides leads to a disorder called Krabbe disease. Krabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare, often fatal degenerative disorder that affects the myelin sheath of the nervous system. Krabbe disease is caused by mutations in the GALC gene, which causes a deficiency of galactosylceramidase. Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression. In infants, the disease is generally fatal before age 2. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.Cerebrosides are glycosphingolipids. There are four types of glycosphingolipids, the cerebrosides, sulfatides, globosides and gangliosides. Cerebrosides have a single sugar group linked to ceramide. The most common are galactocerebrosides (containing galactose), the least common are glucocerebrosides (containing glucose). Galactocerebrosides are found predominantly in neuronal cell membranes. In contrast glucocerebrosides are not normally found in membranes. Instead, they are typically intermediates in the synthesis or degradation of more complex glycosphingolipids. Galactocerebrosides are synthesized from ceramide and UDP-galactose. Excess lysosomal accumulation of glucocerebrosides is found in Gaucher disease.


beta-D-Glucuronoside

Ibuprofen glucuronide is a metabolite of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used for relief of symptoms of arthritis, fever, as an analgesic (pain reliever), especially where there is an inflammatory component, and dysmenorrhea. Ibuprofen is known to have an antiplatelet effect, though it is relatively mild and somewhat short-lived when compared with aspirin or other better-known antiplatelet drugs. (Wikipedia)


5'-Phosphoribosyl-N-formylglycineamide (also known as FGAR or N-Formyl-GAR) is a substrate for Phosphoribosylformylglycinamidine synthase. It is involved in aminoimidazole ribonucleotide biosynthesis and plays a vital role in purine metabolism as well as the conversion of glutamine to glutamate. 5'-Phosphoribosyl-N-formylglycineamide is described as a glycinamide ribonucleotide having a phosphate group at the 5-position and a formyl group on the glycine nitrogen.


2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine is involved in folate biosynthesis. 2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine is created from 2,5-Diaminopyrimidine nucleoside triphosphate by GTP cyclohydrolase I [EC:3.5.4.16]. 2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine can be converted into 2-Amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine. triphosphate by GTP cyclohydrolase I [EC:3.5.4.16]. GTP cyclohydrolase I [EC:3.5.4.16] can also be converted to 6-(3'-Triphosphoryl-1'-methylglyceryl)-7-methyl-7,8-dihydrobiopterin.


Bepotastine

Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion&reg. It is currently undergoing trials in the U.S.


Phytate Sodium

Myo-Inositol hexakisphosphate is an intermediate in inositol phosphate metabolism. It can be generated from D-myo-Inositol 1,3,4,5,6-pentakisphosphate via the enzyme inositol-pentakisphosphate 2-kinase (EC:2.7.1.158). Myo-Inositol hexakisphosphate is also known as phytic acid. It can be used clinically as a complexing agent for removal of traces of heavy metal ions. It acts also as a hypocalcemic agent. Phytic acid is a strong chelator of important minerals such as calcium, magnesium, iron and zinc and can therefore contribute to mineral deficiencies in developing countries. For people with a particularly low intake of essential minerals, especially young children and those in developing countries, this effect can be undesirable. However, dietary mineral chelators help prevent over-mineralization of joints, blood vessels, and other parts of the body, which is most common in older persons. The Journal of Environmental Nutrition (April 2004 volume 27 issue 4) has also stated phytic acid may be considered a phytonutrient, providing an antioxidant effect.


gentamicin

A complex of three different closely related aminoglycoside sulfates, Gentamicins C1, C2, and C1(subA), obtained from Micromonospora purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit protein synthesis (genetic translation). [PubChem]


S-Methylmalonyl-CoA belongs to the class of organic compounds known as acyl coas. These are organic compounds containing a coenzyme A substructure linked to an acyl chain. S-Methylmalonyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). S-Methylmalonyl-CoA has been primarily detected in urine. Within the cell, S-methylmalonyl-CoA is primarily located in the cytoplasm, mitochondria and peroxisome. In humans, S-methylmalonyl-CoA is involved in the threonine and 2-oxobutanoate degradation pathway, the propanoate metabolism pathway, and the valine, leucine and isoleucine degradation pathway. S-Methylmalonyl-CoA is also involved in several metabolic disorders, some of which include the isovaleric aciduria pathway, the maple syrup urine disease pathway, isobutyryl-CoA dehydrogenase deficiency, and the 3-methylglutaconic aciduria type III pathway. Methylmalonyl-CoA is an intermediate in the metabolism of Propanoate. It is a substrate for Malonyl-CoA decarboxylase (mitochondrial), Methylmalonyl-CoA mutase (mitochondrial) and Methylmalonyl-CoA epimerase (mitochondrial).


R-Methylmalonyl-CoA belongs to the class of organic compounds known as acyl coas. These are organic compounds containing a coenzyme A substructure linked to an acyl chain. R-Methylmalonyl-CoA is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). R-Methylmalonyl-CoA has been primarily detected in urine. Within the cell, R-methylmalonyl-CoA is primarily located in the cytoplasm. In humans, R-methylmalonyl-CoA is involved in the threonine and 2-oxobutanoate degradation pathway, the valine, leucine and isoleucine degradation pathway, and the propanoate metabolism pathway. R-Methylmalonyl-CoA is also involved in several metabolic disorders, some of which include the maple syrup urine disease pathway, the 3-methylglutaconic aciduria type IV pathway, 3-methylcrotonyl CoA carboxylase deficiency type I, and 3-hydroxyisobutyric acid dehydrogenase deficiency. Methylmalonyl-CoA is an intermediate in the metabolism of Propanoate. It is a substrate for Malonyl-CoA decarboxylase (mitochondrial), Methylmalonyl-CoA mutase (mitochondrial) and Methylmalonyl-CoA epimerase (mitochondrial).


11beta,21-Dihydroxy-3,20-oxo-5beta-pregnan-18-al is an intermediate in C21-Steroid hormone metabolism. 11beta,21-Dihydroxy-3,20-oxo-5beta-pregnan-18-al is converted from Aldosterone via the enzyme 3-oxo-5beta-steroid 4-dehydrogenase (EC:1.3.99.6). It is then converted to 3alpha,11beta,21-Trihydroxy-20-oxo-5beta-pregnan-18-al via the enzyme 3-alpha-hydroxysteroid dehydrogenase (EC:1.1.1.50).


dihydrocorticosterone

11beta,21-Dihydroxy-5beta-pregnane-3,20-dione is an intermediate in C21-Steroid hormone metabolism. 11beta,21-Dihydroxy-5beta-pregnane-3,20-dione is the 3rd to last step in the synthesis of 3alpha,20alpha,21-Trihydroxy-5beta-pregnane-11-one and is converted from Corticosterone via the enzyme 3-oxo-5beta-steroid 4-dehydrogenase (EC 1.3.99.6). It is then converted to Tetrahydrocorticosterone via the enzyme 3-alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50).


3alpha-Hydroxy-5beta-pregnane-20-one is an intermediate in C21-Steroid hormone metabolism. 3alpha-Hydroxy-5beta-pregnane-20-one is converted from 5beta-Pregnane-3,20-dione via the enzyme 3-alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50). It is then converted to Pregnanediol via the enzyme 3alpha(or 20beta)-hydroxysteroid dehydrogenase (EC 1.1.1.53).


5'-biotinyl-AMP (B-AMP) is the active form of biotin in mammals. In human cells, biotin is essential to maintain metabolic homeostasis and as regulator of gene expression. The vitamin biotin plays an essential role in gluconeogenesis, fatty acid synthesis, and carbohydrate metabolism because of its role as cofactor of five carboxylases; pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), methylcrotonyl-CoA carboxylase, and two forms of acetyl-CoA carboxylase (ACC-1 and ACC-2). Carboxylase biotinylation is catalyzed by the enzyme holocarboxylase synthetase (HCS) through a reaction that involves the transformation of biotin into B-AMP and its subsequent attachment to a specific lysine residue in the carboxylases. B-AMP is also required to activate a signal transduction cascade that includes a soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG). The regulatory role of biotin in the biotin cycle seems to be limited to the expression of proteins involved in the transport and utilization of exogenous vitamin while having no effect on biotinidase mRNA levels, enzyme responsible for biotin recycling during carboxylase turnover. Multiple carboxylase deficiency (MCD) is a life-threatening disease characterized by the lack of carboxylase activities because of deficiency of HCS activity. (PMID: 15905112, 11959985).

5'-adenylic acid monoanhydride with biotin

[3as-(3aa,4b,6aa)]-5'-adenylic acid monoanhydride with hexahydro-2-oxo-1h-thieno[3,4-d]imidazole-4-pentanoate

[3as-(3aa,4b,6aa)]-5'-adenylic acid monoanhydride with hexahydro-2-oxo-1h-thieno[3,4-d]imidazole-4-pentanoic acid


Se-Adenosylselenohomocysteine is an intermediate in Selenoamino acid metabolism. Se-Adenosylselenohomocysteine is the second to last step in the synthesis of Selenohomocystine and is converted from Se-Adenosylselenomethionine via the enzyme Transferases (EC 2.1.1.-). It is then. converted to Selenohomocysteine via the enzyme adenosylhomocysteinase (EC 3.3.1.1).


Gamma-Glutamyl-se-methylselenocysteine, also known as gamma-glutamyl-semc or GGMSC CPD, belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond. Gamma-Glutamyl-se-methylselenocysteine is soluble (in water) and a moderately acidic compound (based on its pKa). Gamma-Glutamyl-se-methylselenocysteine exists in all living organisms, ranging from bacteria to humans. In humans, Gamma-glutamyl-se-methylselenocysteine is involved in the selenoamino acid metabolism pathway. gamma-Glutamyl-Se-methylselenocysteine is an intermediate in selenoamino acid metabolism(KEGG ID C05695). It is generated from Se-methyl-selenocysteine via the enzyme gamma-glutamyltranspeptidase [EC:2.3.2.2].


doxycycline

Doxycycline is only found in individuals that have used or taken this drug. It is a synthetic tetracycline derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria (malaria, falciparum). [PubChem]Doxycycline, like minocycline, is lipophilic and can pass through the lipid bilayer of bacteria. Doxycycline reversibly binds to the 30 S ribosomal subunits and possibly the 50S ribosomal subunit(s), blocking the binding of aminoacyl tRNA to the mRNA and inhibiting bacterial protein synthesis. Doxycycline prevents the normal function of the apicoplast of Plasmodium falciparum, a malaria causing organism.


11-Dehydrocorticosterone is a mineral corticosteroid. The conversion of inactive 11-ketoglucocorticoids such as 11-dehydrocorticosterone) into active 11b-hydroxyglucocorticoids (such as corticosterone) is catalyzed by 11beta-hydroxysteroid dehydrogenase (11b-HSD1, EC 1.1.1.146), which is expressed in many tissues and plays an important role in metabolically relevant tissues such as the liver, adipose tissue, skeletal muscles and possibly kidney. Chronically elevated local glucocorticoid action as a result of increased 11beta-HSD1 activity rather than elevated systemic glucocorticoid levels has been associated with metabolic syndrome, which is characterized by obesity, insulin resistance, type 2 diabetes and cardiovascular complications. Recent studies indicate that compounds inhibiting 11beta-HSD1 activity ameliorate the adverse effects of excessive glucocorticoid concentrations on metabolic processes, providing promising opportunities for the development of therapeutic interventions. 11-dehydrocorticosterone and corticosterone display antinatriuretic activity, although 11-dehydrocorticosterone is generally a more potent sodium retainer than corticosterone. (PMID: 17584152, Endocr Metab Immune Disord Drug Targets. 2007 Jun;7(2):125-40.).


Citrullinemia Type I,Disease

biolink:Pathway biolink:OntologyClass biolink:BiologicalProcess biolink:Occurrent biolink:BiologicalProcessOrActivity biolink:BiologicalEntity biolink:ThingWithTaxon biolink:NamedThing biolink:PhysicalEssenceOrOccurrent

Citrullinemia Type I, (Argininosuccinate Synthetase Deficiency, Citrullinuria, Citrullinemia, ASS) is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in the liver. These reactions process excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. Citrullinemia Type I is an autosomal recessive disease caused by mutation in the ASS gene which codes for argininosuccinate synthetase. A deficiency in this enzyme results in accumulation of citruilline as well as glycine and orotic acid in urine. Infants appear normal at birth, but within the first week of life symptoms such as feeding difficulties, irritability, hypotonia, seizures, and vomiting present and eventually lead to premature death.


Carbamoyl Phosphate Synthetase Deficiency,Disease

Carbamoyl phosphate synthetase (CPS) deficiency (Carbamoyl phosphate synthetase I deficiency) is a urea cycle defect that results from a deficiency in an enzyme that mediates the normal path for incorporation of ammonia. Carbamoyl phosphate is derived from catabolism of amino acids into a 1-carbon compound, in which the carbon atom is derived from bicarbonate. The process is exclusively mitochondrial and requires the expenditure of two ATP molecules. Two hepatocellular enzymes exist: CPS I and CPS II. CPS I is exclusively intramitochondrial, and its deficiency is responsible for the disease. CPS I is the most plentiful single protein in hepatic mitochondria, accounting for about 20% of the matrix protein. CPS II is exclusively cytosolic and is an important enzyme in de novo synthesis of pyrimidine nucleotides. The regulation of CPS I activity depends on the levels of N -acetylglutamate.  In patients with homozygous CPS I deficiency, the ability to fix waste nitrogen is completely absent, resulting in increasing levels of free ammonia with the attendant effects on the CNS. A recent molecular and functional examination of the mutational effects showed that, although some mutations affect both substrate affinity and efficiency of the reaction, others affect one more than the other. Some mutations are associated with enhanced RNA instability, which leads to diminished protein synthesis.  The hepatic urea cycle is the major route for waste nitrogen disposal. Waste nitrogen is chiefly generated from protein and amino acid metabolism. Low-level synthesis of certain cycle intermediates in extrahepatic tissues also makes a small contribution to waste nitrogen disposal. A portion of the cycle is mitochondrial in nature; mitochondrial dysfunction may impair urea production and may result in hyperammonemia. Overall, activity of the cycle is regulated by the rate of synthesis of N -acetylglutamate, the enzyme activator of CPS I, which initiates incorporation of ammonia into the cycle.


Argininosuccinic Aciduria,Disease

Argininosuccinic Aciduria, (Argininosuccinase Deficiency, Argininosuccinate Lyase Deficiency, ASL Deficiency) is an autosomal recessive disorder caused by a mutation in the ASL gene which codes for argininosuccinate lyase. It results in accumulation of citrulline, arginosuccinic acid, L-arginine, and L-glutamic acid in plasma as well as ammonia in blood. Infants are lethargic and unwilling to eat. They may develop seizures, coma, and failure to thrive as toxic ammonia accumulates.


Glycine and Serine Metabolism,Metabolic

This pathway describes the synthesis and breakdown of several small amino acids, including glycine, serine, and cysteine. All of these compounds share common intermediates and almost all can be biosynthesized from one another. Serine and glycine are not essential amino acids and can be synthesized from several routes. On the other hand, cysteine is a conditionally essential amino acid, meaning that it can be endogenously synthesized but insufficient quantities may be produced due to certain diseases or conditions. Serine is central to the synthesis and breakdown of the other two amino acids. Serine can be synthesized via glycerate, which can be converted into glycerate 3-phosphate (via glycerate kinase), which in turn is converted into phosphohydroxypyruvate by phosphoglycerate dehydrogenase and then phosphoserine (via phosphoserine transaminase) and finally to serine (via phosphoserine phosphatase). The serine synthesized via this route can be used to create cysteine and glycine through the homocysteine cycle. In the homocysteine cycle, cystathionine beta-synthase catalyzes the condensation of homocysteine and serine to give cystathionine. Cystathionine beta-lyase then converts this double amino acid to cysteine, ammonia, and alpha-ketoglutarate. Glycine is biosynthesized in the body from the amino acid serine. In most organisms, the enzyme serine hydroxymethyltransferase (SHMT) catalyzes this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. Glycine can be degraded via three pathways. The predominant pathway in animals involves the glycine cleavage system, also known as the glycine decarboxylase complex or GDC. This system is usually triggered in response to high concentrations of glycine. The system is sometimes referred to as glycine synthase when it runs in the reverse direction to produce glycine. The glycine cleavage system consists of four weakly interacting proteins: T, P, L and H-proteins. The glycine cleavage system leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step in this degradation pathway is the reverse of glycine biosynthesis from serine with serine hydroxymethyltransferase (SHMT). The serine generated via glycine is then converted into pyruvate by the enzyme known as serine dehydratase. In the third route to glycine degradation, glycine is converted into glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase into oxalate in an NAD+-dependent reaction.


Pterine Biosynthesis,Metabolic

Folates are essential cofactors that provide one-carbon moieties in various states of reduction for biosynthetic reactions. The processes shown in this pathway include transport reactions by which folates are taken up by cells and moved intracellularly, folate conjugation with glutamate (required for folate retention within a cell), as well as the synthesis of pterines, which are used in folate synthesis. Two branches are depicted: Pterin synthesis and Folate biosynthesis. In pterin synthesis, GTP is the precursor for pterin biosynthesis. The enzyme GTP-cyclohydrolase I produces dihydroneopterin triphosphate from GTP as the first step. The product is then dephosphorylated to dihydroneopterin and yields, after removal of a C2-residue from the C3-side chain 6- hydroxymethyldihydropterin, which is the precursor for folate biosynthesis. In terms of folate biosynthesis, the basic steps are: folate → dihydrofolate → tetrahydrofolate ↔ methylene-THF → methyl-THF. More specifically, the pathway leading to the formation of tetrahydrofolate (FH4) begins when folate (F) is reduced to dihydrofolate (DHF) (FH2), which is then reduced to THF. Dihydrofolate reductase catalyses the last step. Vitamin B3 in the form of NADPH is a necessary cofactor for both steps of the synthesis. Methylene-THF (CH2FH4) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH3-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. Another form of THF, formyl-THF (or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Finally, histidine can donate a single carbon to THF to form methenyl-THF.


Tyrosine Metabolism,Metabolic

The tyrosine metabolism pathway describes the many ways in which tyrosine is catabolized or transformed to generate a wide variety of biologically important molecules. In particular, tyrosine can be metabolized to produce hormones such as thyroxine and triiodothyronine or it can be metabolized to produce neurotransmitters such as L-DOPA, dopamine, adrenaline, or noradrenaline. Tyrosine can also serve as a precursor of the pigment melanin and for the formation of Coenzyme Q10. Additionally, tyrosine can be catabolized all the way down into fumarate and acetoacetate. This particular pathway for tyrosine degradation starts with an alpha-ketoglutarate-dependent transamination reaction of tyrosine, which is mediated through the enzyme known as tyrosine transaminase. This process generates p-hydroxyphenylpyruvate. This aromatic acid is then acted upon by p-hydroxylphenylpyruvate-dioxygenase which generates the compound known as homogentisic acid or homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a unique dioxygenase enzyme known as homogentisic acid 1,2-dioxygenase is required. Through this enzyme, maleylacetoacetate is created from the homogentisic acid precursor.  The accumulation of excess homogentisic acid and its oxide (named alkapton) in the urine of afflicted individuals can lead to a condition known as alkaptonuria.  This genetic condition, also known as an inborn error of metabolism or IEM, occurs if there are mutations in the homogentisic acid 1,2-dioxygenase gene. After the breakdown of homogentisate is achieved, maleylacetoacetate is then attacked by the enzyme known as maleylacetoacetate-cis-trans-isomerase, which generates fumarylacetate. This isomerase catalyzes the rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase uses glutathione as a coenzyme or cofactor. The resulting product, fumarylacetoacetate, is then split into acetoactate and fumarate via the enzyme known as fumarylacetoacetate-hydrolase through the addition of a water molecule. Through this set of reactions fumarate and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA, which in turn can be oxidized by the citric acid cycle (also known as the TCA cycle) or used for fatty acid synthesis. Other aspects of tyrosine metabolism include the generation of catecholamines. In this process, the enzyme known as tyrosine hydroxylase (or AAAH or TYH) catalyzes the conversion of tyrosine to L-DOPA. The L-DOPA can then be converted via the enzyme DOPA decarboxylase (DDC) to dopamine. Dopamine can then be converted to 3-methoxytyramine via the action of catechol-O-methyltransferase (COMT). Dopamine can also be converted to norepinephrine (noradrenaline) through the action of the enzyme known as dopamine beta hydroxylase (DBH).  Norepinephrine can then be converted to epinephrine (adrenaline) through the action of phenyethanolamine N-methyltransferase (PNMT). Catecholamines such as L-DOPA, dopamine and methoxytyramine are produced mainly by the chromaffin cells of the adrenal medulla and by neuronal cells found in the brain. For example, dopamine, which acts as a neurotransmitter, is mostly produced in neuronal cell bodies in the ventral tegmental area and the substantia nigra while epinephrine is produced in neurons in the human brain that express PMNT. Catecholamines typically have a half-life of a few minutes in the blood. They are typically degraded via catechol-O-methyltransferases (COMT) or by deamination via monoamine oxidases (MAO). Another important aspect of tyrosine metabolism includes the production of melanin. Melanin is produced through a mechanism known as melanogenesis, a process that involves the oxidation of tyrosine followed by the polymerization of these oxidation by-products. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are three types of melanin: pheomelanin, eumelanin, and neuromelanin of which eumelanin is the most common. Melanogenesis, especially in the skin, is initiated through the exposure to UV light. Melanin is the primary pigment that determines skin color. Melanin is also found in hair and the pigmented tissue underlying the iris. The first step in the synthesis for both eumelanins and pheomelanins is the conversion of tyrosine to dopaquinone by the enzyme known as tyrosinase. The resulting dopaquinone can combine with cysteine to produce cysteinyldopa, which then polymerizes to form pheomelanin. Dopaquinone can also form lecuodopachrome, which then can be converted to dopachrome (a cyclization product) and this eventually becomes eumelanin. Tyrosine plays a critical role in the synthesis of thyroid hormones. Thyroid hormones are produced and released by the thyroid gland and include triiodothyronine (T3) and thyroxine (T4). These two hormones are responsible for regulating metabolism. Thyroxine was discovered and isolated by Edward Calvin Kendall in 1915. Thyroid hormones are produced by the follicular cells of the thyroid gland through the action of thyroperoxidase, which iodinates reactive tyrosine residues on thyroglobulin.  Proteolysis of the thyroglobulin in cellular lysosomes releases the small molecule thyroid hormones. In mammals, tyrosine can be formed from dietary phenylalanine by the enzyme phenylalanine hydroxylase, found in large amounts in the liver. Phenylalanine is considered an essential amino acid, while tyrosine (which can be endogenously synthesized) is not.  In plants and most microbes, tyrosine is produced via prephenate, an intermediate that is produced as part of the shikimate pathway.


beta-Alanine Metabolism,Metabolic

Beta-alanine, 3-aminopropanoic acid, is a non-essential amino acid. Beta-Alanine is formed by the proteolytic degradation of beta-alanine containing dipeptides: carnosine, anserine, balenine, and pantothenic acid (vitamin B5). These dipeptides are consumed from protein-rich foods such as chicken, beef, pork, and fish. Beta-Alanine can also be formed in the liver from the breakdown of pyrimidine nucleotides into uracil and dihydrouracil and then metabolized into beta-alanine and beta-aminoisobutyrate. Beta-Alanine can also be formed via the action of aldehyde dehydrogenase on beta-aminoproionaldehyde which is generated from various aliphatic polyamines. Under normal conditions, beta-alanine is metabolized to aspartic acid through the action of glutamate decarboxylase. It addition, it can be converted to malonate semialdehyde and thereby participate in propanoate metabolism. Beta-Alanine is not a proteogenic amino acid. This amino acid is a common athletic supplementation due to its belief to improve performance by increased muscle carnosine levels.


Phenylalanine and Tyrosine Metabolism,Metabolic

In man, phenylalanine is an essential amino acid which must be supplied in the dietary proteins.  Once in the body, phenylalanine may follow any of three paths.  It may be (1) incorporated into cellular proteins, (2) converted to phenylpyruvic acid, or (3) converted to tyrosine.  Tyrosine is found in many high protein food products such as soy products, chicken, turkey, fish, peanuts, almonds, avocados, bananas, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds, and sesame seeds.  Tyrosine can be converted into L-DOPA, which is further converted into dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline).  Depicted in this pathway is the conversion of phenylalanine to phenylpyruvate (via amino acid oxidase or tyrosine amino transferase acting on phenylalanine), the incorporation of phenylalanine and/or tyrosine into polypeptides (via tyrosyl tRNA synthetase and phenylalyl tRNA synthetase) and the conversion of phenylalanine to tyrosine via phenylalanine hydroxylase.  This reaction functions both as the first step in tyrosine/phenylalanine catabolism by which the body disposes of excess phenylalanine, and as a source of the amino acid tyrosine.  The decomposition of L-tyrosine begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate.  The next oxidation step catalyzed by p-hydroxylphenylpyruvate-dioxygenase creates homogentisate.  In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase, is required to create maleylacetoacetate.  Fumarylacetate is created by the action maleylacetoacetate-cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation.  This cis-trans-isomerase contains glutathione as a coenzyme.  Fumarylacetoacetate is finally split via fumarylacetoacetate-hydrolase into fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate).


Ammonia Recycling,Metabolic,Ammonia can be rerouted from the urine and recycled into the body for use in nitrogen metabolism. Glutamate and glutamine play an important role in this process. There are many other processes that act to recycle ammonia. asparaginase recycles ammonia from asparagine. Glycine cleavage system generates ammonia from glycine. Histidine ammonia lyase forms ammonia from histidine. Serine dehydratase also produces ammonia by cleaving serine.


Nucleotide Sugars Metabolism,Metabolic

Nucleotide sugars are defined as any nucleotide in which the distal phosphoric residue of a nucleoside 5'-diphosphate is in glycosidic linkage with a monosaccharide or monosaccharide derivative. There are nine sugar nucleotides and they can be classified depending on the type of the nucleoside forming them: UDP-Glc, UDP-Gal, UDP-GlcNAc, UDP-GlcUA, UDP- Xyl, GDP-Man, GDP-Fuc and CMP-NeuNAc. Turning back now to the pathway in question, namely the nucleotide sugar metabolism pathway, it should be noted that the nucleotide sugars play an important role. Indeed, they are donors of certain important residues of sugar which are vital to glycosylation and by extension tot the production of polysaccharides. This process produces the substrates for glycosyltransferases. These sugars have several additional roles. For example, nucleotide sugars serve a vital purpose as the intermediates in interconversions of nucleotide sugars that result in the creation and activation of certain sugars necessary in the glycosylation reaction in certain organisms. Moreover, the process of glycosylation is attributed mostly (though not entirely) to the endoplasmic reticulum/golgi apparatus. Logically then, due to the important role of nucleotide sugars in glycosylation, a plethora of transporters exist which displace the sugars from their point of production, the cytoplasm, to where they are needed. In the case, the endoplasmic reticulum and golgi apparatus.


Inositol Metabolism,Metabolic

Inositol (also known as myo-inositol) is a carbocyclic polyol that plays an important role as the structural basis for a number of secondary messengers in eukaryotic cells, including inositol phosphates, phosphatidylinositol (PI) and phosphatidylinositol phosphate (PIP) lipids. It is found in many foods, in particular, in cereals with high bran content, nuts, beans, and fruit, especially cantaloupe melons and oranges. Inositol is not considered a vitamin itself because it can be synthesised by the body. Myo-Inositol is synthesized from glucose-6-phosphate (G-6-P) in two steps. First, G-6-P is isomerised by inositol-3-phosphate synthase (ASYNA1) to myo-inositol 3-phosphate, which is then dephosphorylated by inositol monophosphatase (IMPase 1) to give free myo-inositol. The synthesis of phosphatidylinositol is catalyzed by phosphatidylinositol synthase and involves CDP-diacylglycerol and myo-inositol. Phosphatidylinositol phosphate lipids are a product of class I, II and III phosphoinositide 3-kinases (PI 3-kinases) acting on phosphatidylinositol. Many inositol phosphates are made by the hydrolysis of phosphatidylinositol phosphates by phospholipase C. They may also be synthesized or remodeled via various kinases and phosphatases.


Catecholamine Biosynthesis,Metabolic

The Catecholamine Biosynthesis pathway depicts the synthesis of catecholamine neurotransmitters. Catecholamines are chemical hormones released from the adrenal glands as a response to stress that activate the sympathetic nervous system. They are composed of a catechol group and are derived from amino acids. The commonly found catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. They are synthesized in catecholaminergic neurons by four enzymes, beginning with tyrosine hydroxylase (TH), which generates L-DOPA from tyrosine. The L-DOPA is then converted to dopamine via aromatic L-amino acid decarboxylase (AADC), which becomes  norepinephrine via dopamine beta-hydroxylase (DBH); and finally is converted to epinephrine via phenylethanolamine N-methyltransferase (PNMT).


Cysteine Metabolism,Metabolic,The semi-essential amino aid cysteine is tightly regulated in the body to ensure proper levels for metabolism but maintaining levels below toxic thresholds. Cysteine can be obtained from diet or synthesized from  O-acetyl-L-serine. Cystine is the dimeric form of cysteine. Cysteine is a precursor for protein synthesis and an antioxidant. Impaired cysteine metabolism has been linked with neurodegenerative disorders.


Glutathione Metabolism,Metabolic

Glutathione (GSH) is an low-molecular-weight thiol and antioxidant in various species such as plants, mammals and microbes. Glutathione plays important roles in nutrient metabolism, gene expression, etc. and sufficient protein nutrition is important for maintenance of GSH homeostasis. Glutathione is synthesized from glutamate, cysteine, and glycine sequentially by gamma-glutamylcysteine synthetase and GSH synthetase. L-Glutamic acid and cysteine are synthesized to form gamma-glutamylcysteine by glutamate-cysteine ligase that is powered by ATP. Gamma-glutamylcysteine and glycine can be synthesized to form glutathione by enzyme glutathione synthetase that is powered by ATP, too. Glutathione exists oxidized (GSSG) states and in reduced (GSH) state. Oxidation of glutathione happens due to relatively high concentration of glutathione within cells.


Propanoate Metabolism,Metabolic

This pathway depicts the metabolism of propionic acid. Propionic acid in mammals typically arises from the production of the acid by gut or skin microflora. Propionic acid producing bacteria (Propionibacterium sp.) are particularly common in sweat glands of mammals.  After entering a cell, the propionic acid (propanoate) then enters the mitochondria where it is converted into propanol adenylate (or propionyl adenylate or propionyl-AMP) via propionyl-CoA synthetase and acetyl-CoA synthetase. The propionyl adenylate then is converted into propionyl coenzyme A (propionyl-CoA) via the same pair of enzymes. Propionyl-CoA is a relatively common compound that can also arise from the metabolic breakdown of fatty acids containing odd numbers of carbon atoms. Propionyl-CoA is also known to arise from the breakdown of some amino acids. Since propanoate has three carbons, propionyl-CoA cannot directly enter the beta-oxidation cycle (which requires two carbons from acetyl-CoA). Therefore, in most vertebrates, propionyl-CoA is carboxylated into D-methylmalonyl-CoA via propionyl-CoA carboxylase. The resulting compound is isomerized into L-methylmalonyl-CoA via methylmalonyl-CoA epimerase.  A vitamin B12-dependent enzyme, called methylmalonyl CoA mutase catalyzes the rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which is an intermediate of the citric acid cycle. Also depicted in this pathway is another propionic acid homolog called hydroxypropanoic acid (hydroxypropionate). This compound is also produced by bacteria and imported into cells. Hydroxypropionate can be converted into 3-hydroxypropionyl-CoA. This compound can be either enzymatically converted to acryloyl-CoA and then to propionyl-CoA or it can spontaneously convert to malonyl-CoA. Malonyl-CoA can convert into acetyl-CoA (via acetyl-CoA carboxylase in the cytoplasm or malonyl carboxylase in the mitochondria) whereupon it may enter a variety of pathways. In a rare genetic metabolic disorder called propionic acidemia, propionate acts as a metabolic toxin in liver cells by accumulating in the liver mitochondria as propionyl-CoA and its derivative methylcitrate. Both propionyl-CoA and methylcitrate are known TCA inhibitors. Glial cells are particularly susceptible to propionyl-CoA accumulation. In fact, when propionate is infused into rat brains and take up by the glial cells, it leads to behavioural changes that resemble autism (PMID: 16950524).


Vitamin B6 Metabolism,Metabolic

As is commonly known there are many vitamins, the vitamin B complex group being one of the most well known. An important vitamin B complex group vitamin is vitamin B6, which is water-soluble. Moreover, this vitamin comes in various forms, one of which is an active form, known by the name pyridoxal phosphate or PLP. PLP serves as cofactor in a variety of reactions including from amino acid metabolism, (in particular in reactions such as transamination, deamination, and decarboxylation). To complicate matters however, there are in fact seven alternate forms of this same vitamin. These include pyridoxine (PN), pyridoxine 5’-phosphate (PNP), pyridoxal (PL), pyridoxamine (PM), pyridoxamine 5’-phosphate (PMP), 4-pyridoxic acid (PA), and the aforementioned pyridoxal 5’-phosphate (PLP). One of these forms, PA, is in fact a catabolite whose presence is found in excreted urine. For a person to absorb some of these active forms of vitamin B6 such as PLP or PMP they must first be dephosphorylized. This done via an alkaline enzyme phosphatase. There are a wide variety of biproducts from the metabolism in question, most of which find there ways into the urine and from there are excreted. One such biproduct is 4-pyridoxic acid. In fact this last biproduct is found in such large quantities that estimates of vitamin B6 metabolism birproducts show that 4-pyridoxic acid is as much as 40-60% of all the biproducts.Of course, it is not the only product of metabolism. Others include,include pyridoxal, pyridoxamine, and pyridoxine.


Alpha Linolenic Acid and Linoleic Acid Metabolism,Metabolic

Linoleic acid (LNA) is a polyunsaturated fatty acid (PUFA) precursor to the longer n−6 fatty acids commonly known as omega-6 fatty acids. Omega-6 fatty acids are characterized by a carbon-carbon double bond at the sixth carbon from the methyl group. Similarly, the PUFA alpha-linoleic acid (ALA) is the precursor to n-3 fatty acids known as omega-3 fatty acids which is characterized by a carbon-carbon double bond at the third carbon from the methyl group. Both LNA and ALA are essential dietary requirements for all mammals since they cannot be synthesized natively in the body. Both undergo a series of similar conversions to reach their final fatty acid form. LNA enters the cell and is catalyzed to gamma-linolenic acid (GLA) by acyl-CoA 6-desaturase (delta-6-desaturase/fatty acid desaturase 2). GLA is then converted to dihomo-gammalinolenic acid (DGLA) by elongation of very long chain fatty acids protein 5 (ELOVL5). DGLA is then converted to arachidonic acid (AA) by acyl-CoA (8-3)-desaturase (delta-5-desaturase/fatty acid desaturase 1). Arachidonic acid is then converted to a series of short lived metabolites called eicosanoids before finally reaching it's final fatty acid form.


Arginine and Proline Metabolism,Metabolic

The arginine and proline metabolism pathway illustrates the biosynthesis and metabolism of several amino acids including arginine, ornithine, proline, citrulline, and glutamate in mammals. In adult mammals, the synthesis of arginine takes place primarily through the intestinal-renal axis (PMID: 19030957). In particular, the amino acid citrulline is first synthesized from several other amino acids (glutamine, glutamate, and proline) in the mitochondria of the intestinal enterocytes (PMID: 9806879). The mitochondrial synthesis of citrulline starts with the deamination of glutamine to glutamate via mitochondrial glutaminase. The resulting mitochondrial glutamate is converted into 1-pyrroline-5-carboxylate via pyrroline-5-carboxylate synthase (P5CS). Alternately, the 1-pyrroline-5-carboxylate can be generated from mitochondrial proline via proline oxidase (PO). Ornithine aminotransferase (OAT) then converts the mitochondrial 1-pyrroline-5-carboxylate into ornithine and the enzyme ornithine carbamoyltransferase (OCT -- using carbamoyl phosphate) converts the ornithine to citrulline (PMID: 19030957). After this, the mitochondrial citrulline is released from the small intestine enterocytes and into the bloodstream where it is taken up by the kidneys for arginine production. Once the citrulline enters the kidney cells, the cytosolic enzyme argininosuccinate synthetase (ASS) will combine citrulline with aspartic acid to generate argininosuccinic acid. After this step, the enzyme argininosuccinate lyase (ASL) will remove fumarate from argininosuccinic acid to generate arginine. The resulting arginine can either stay in the cytosol where it is converted to ornithine via arginase I (resulting in the production of urea) or it can be transported into the mitochondria where it is decomposed into ornithine and urea via arginase II.  The resulting mitochondrial ornithine can then be acted on by the enzyme ornithine amino transferase (OAT), which combines alpha-ketoglutarate with ornithine to produce glutamate and 1-pyrroline-5-carboxylate.  The mitochondrial enzyme pyrroline-5-carboxylate dehydrogenase (P5CD) acts on the resulting 1-pyrroline-5-carboxylate (using NADPH as a cofactor) to generate glutamate. Alternately, the mitochondrial 1-pyrroline-5-carboxylate can be exported into the kidney cell’s cytosol where the enzyme pyrroline-5-carboxylate reductase (P5CR) can convert it to proline. While citrulline-to-arginine production primarily occurs in the kidney, citrulline is readily converted into arginine in other cell types, including adipocytes, endothelial cells, myocytes, macrophages, and neurons.  Interestingly, chickens and cats cannot produce citrulline via glutamine/glutamate due to a lack of a functional pyrroline-5-carboxylate synthase (P5CS) in their enterocytes (PMID: 19030957).


Taurine and Hypotaurine Metabolism,Metabolic

There is an organic acid known as Taurine, which is a derivative product of sulfhydryl amino acid (which contains sulfur), as well as cysteine.  The synthesis or metabolism in mammalian systems of this acid transpires within the pancreas in such a fashion that it utilizes a pathway known as the cysteine sulfinic acid pathway.To put this process in context, its occurrence is often seen in vivo, in hepatocytes, and is fundamental in the cyclical process of recovering bile acids from the intenstine, turning them back into salts and returning them to the bile. In essence the cysteine pathway induces a sulfhydryl group to be oxidized, creating cysteine sulfinic acid, by utilizing the appropriate enzymes (ie cysteine dioxygenase). This new acid undergoes decarboxylation creating a new compound: hypotaurine. This process goes on as Taurine now is subjected to conjugation vis a vis its amino terminal group. This includes acids such as chenodeoxycholic acid and cholic acid, and in turn the formation of bile salts occurs.Moreover, this entire process can be catalyzed via bile acid and a special amino acid N-acetyltransferase.


Steroid Biosynthesis,Metabolic

The steroid biosynthesis (or cholesterol biosynthesis) pathway is an anabolic metabolic pathway that produces steroids from simple precursors. It starts with the mevalonate pathway, where acetyl-CoA and acetoacetyl-CoA are the first two building blocks. These compounds are joined together via the enzyme hydroxy-3-methylgutaryl (HMG)-CoA synthase to produce the compound known as hydroxy-3-methylgutaryl-CoA (HMG-CoA). This compound is then reduced to mevalonic acid via the enzyme HMG-CoA reductase. It is important to note that HMG-CoA reductase is the protein target of many cholesterol-lowering drugs called statins (PMID: 12602122). The resulting mevalonic acid (or mevalonate) is then phosphorylated by the enzyme known as mevalonate kinase to form mevalonate-5-phosphate, which is then phosphorylated again by phosphomevalonate kinase to form mevolonate-5-pyrophsophate. This pyrophosphorylated compound is subsequently decarboxylated via the enzyme mevolonate-5-pyrophsophate decarboxylase to form isopentylpyrophosphate (IPP). IPP can also be isomerized (via isopentenyl-PP-isomerase) to form dimethylallylpyrophosphate (DMAPP). IPP and DMAPP can both donate isoprene units, which can then be joined together to make farnesyl and geranylgeranyl intermediates. Specifically, three molecules of IPP condense to form farnesyl pyrophosphate through the action of the enzyme known as geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form a molecule known as squalene by the action of the enzyme known as squalene synthase in the cell’s endoplasmic reticulum. The enzyme oxidosqualene cyclase then cyclizes squalene to form lanosterol. Lanosterol is a tetracyclic triterpenoid, and serves as the framework from which all steroids are derived. 14-Demethylation of lanosterol by a cytochrome P450 enzyme known as CYP51 eventually yields cholesterol. Cholesterol is the central steroid in human biology. It can be obtained from animal fats consumed in the diet or synthesized de novo (as described above). Cholesterol is an essential constituent of lipid bilayer membranes (where it forms cholesterol esters) and is the starting point for the biosynthesis of steroid hormones, bile acids and bile salts, and vitamin D. Steroid hormones are mostly synthesized in the adrenal gland and gonads. They regulate energy metabolism and stress responses (via glucocorticoids such as cortisol), salt balance (mineralocorticoids such as aldosterone), and sexual development and function (via androgens such as testosterone and estrogens such as estradiol). Bile acids and bile salts (such as taurocholate) are mostly synthesized in the liver. They are released into the intestine and function as detergents to solubilize dietary fats. Cholesterol is the main constituent of atheromas. These are the fatty lumps found in the walls of arteries that occur in atherosclerosis and, when ruptured, can cause heart attacks.


Porphyrin Metabolism,Metabolic

This pathway depicts the synthesis and breakdown of porphyrin. The porphyrin ring is the framework for the heme molecule, the pigment in hemoglobin and red blood cells. The first reaction in porphyrin ring biosynthesis takes place in the mitochondria and involves the condensation of glycine and succinyl-CoA by delta-aminolevulinic acid synthase (ALAS). Delta-aminolevulinic acid (ALA) is also called 5-aminolevulinic acid. Following its synthesis, ALA is transported into the cytosol, where ALA dehydratase (also called porphobilinogen synthase) dimerizes 2 molecules of ALA to produce porphobilinogen. The next step in the pathway involves the condensation of 4 molecules of porphobilinogen to produce hydroxymethylbilane (also known as HMB). The enzyme that catalyzes this condensation is known as porphobilinogen deaminase (PBG deaminase). This enzyme is also called hydroxymethylbilane synthase or uroporphyrinogen I synthase. Hydroxymethylbilane (HMB) has two main fates. Most frequently it is enzymatically converted into uroporphyrinogen III, the next intermediate on the path to heme. This step is mediated by two enzymes: uroporphyrinogen synthase and uroporphyrinogen III cosynthase. Hydroxymethylbilane can also be non-enzymatically cyclized to form uroporphyrinogen I. In the cytosol, the uroporphyrinogens (uroporphyrinogen III or uroporphyrinogen I) are decarboxylated by the enzyme uroporphyrinogen decarboxylase. These new products have methyl groups in place of the original acetate groups and are known as coproporphyrinogens. Coproporphyrinogen III is the most important intermediate in heme synthesis. Coproporphyrinogen III is transported back from the cytosol into the interior of the mitochondria, where two propionate residues are decarboxylated (via coproporphyrinogen-III oxidase), which results in vinyl substituents on the 2 pyrrole rings. The resulting product is called protoporphyrinogen IX. The protoporphyrinogen IX is then converted into protoporphyrin IX by another enzyme called protoporphyrinogen IX oxidase. The final reaction in heme synthesis also takes place within the mitochondria and involves the insertion of the iron atom into the ring system generating the molecule known heme b. The enzyme catalyzing this reaction is known as ferrochelatase. The largest repository of heme in the body is in red blood cells (RBCs). RBCs have a life span of about 120 days. When the RBCs have reached the end of their useful lifespan, the cells are engulfed by macrophages and their constituents recycled or disposed of.  Heme is broken down when the heme ring is opened by the enzyme known as heme oxygenase, which is found in the endoplasmic reticulum of the macrophages. The oxidation process produces the linear tetrapyrrole biliverdin, ferric iron (Fe3+), and carbon monoxide (CO). The carbon monoxide (which is toxic) is eventually discharged through the lungs. In the next reaction, a second methylene group (located between rings III and IV of the porphyrin ring) is reduced by the enzyme known as biliverdin reductase, producing bilirubin. Bilirubin is significantly less extensively conjugated than biliverdin. This reduction causes a change in the colour of the molecule from blue-green (biliverdin) to yellow-red (bilirubin). In hepatocytes, bilirubin-UDP-glucuronyltransferase (bilirubin-UGT) adds two additional glucuronic acid molecules to bilirubin to produce the more water-soluble version of the molecule known as bilirubin diglucuronide. In most individuals, intestinal bilirubin is acted on by the gut bacteria to produce the final porphyrin products, urobilinogens and stercobilins. These are excreted in the feces. The stercobilins oxidize to form brownish pigments which lead to the characteristic brown colour found in normal feces. Some of the urobilinogen produced by the gut bacteria is reabsorbed and re-enters the circulation. These urobilinogens are converted into urobilins that are then excreted in the urine which cause the yellowish colour in urine.


Phospholipid Biosynthesis,Metabolic

This pathway describes the synthesis of the common phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and cardiolipins. Phospholipids can be synthesized by two mechanisms. One utilizes a CDP-activated polar head group for attachment to the phosphate of phosphatidic acid. The other utilizes CDP-activated 1,2-diacylglycerol and an inactivated polar head group. Phospholipids are synthesized in the ER membrane from cytosolic precursors. Two fatty acids linked to coenzyme A (CoA) carriers are first joined to glycerol-3-phosphate, yielding phosphatidic acid, which is simultaneously inserted into the membrane. A phosphatase then converts phosphatidic acid to diacylglycerol. The attachment of different polar head groups to diacylglycerol then results in formation of phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine. Phosphatidylinositol is formed from phosphatidic acid, rather than from diacylglycerol. Initially, most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone. However, the fatty acid distribution at the C–1 and C–2 positions of glycerol within phospholipids is continually in flux, owing to phospholipid degradation and the continuous phospholipid remodeling that occurs while these molecules are in membranes. In many cases the acyl group which was initially transferred to glycerol, by the action of the acyl transferases, is not the same acyl group present in the phospholipid when it resides within a membrane. The remodeling of acyl groups in phospholipids is the result of the action of phospholipase A1 (PLA1) and phospholipase A2 (PLA2). The most commonly added alcohols (serine, ethanolamine and choline) also contain nitrogen that may be positively charged, whereas, glycerol and inositol do not.


Pantothenate and CoA Biosynthesis,Metabolic

Panthothenate (vitamin B5) is the precursor of coenzyme A and is the prosthetic group of acyl carrier protein (ACP). Its name is derived from the Greek pantothen meaning "from everywhere" and small quantities of pantothenic acid are found in nearly every foodstuff. Coenzyme A (CoA) may act as an acyl group carrier to form acetyl-CoA and other related compounds and is used as a way to transport carbon atoms within the cell. CoA is important in energy metabolism for pyruvate to enter TCA cycle as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine. About 85% of dietary pantothenic acid is as CoA or phosphopentetheine. In the intestinal lumen, these undergo hydrolysis to phosphopantetheine, then pantetheine. Intestinal mucosal cells have high pantetheinase activity and rapidly hydrolyze pantetheine to yield free pantothenic acid. Coenzyme A is synthesized in a five-step process from pantothenate. First, antothenate (Vitamin B5) is phosphorylated to 4'-phosphopantothenate by the enzyme pantothenate kinase, next a cysteine is added to 4'-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetase to form 4'-phospho-N-pantothenoylcysteine (PPC). In the next step, PPC is decarboxylated to 4'-phosphopantetheine by phosphopantothenoylcysteine decarboxylase. In the fourth step, 4'-phosphopantetheine is adenylylated to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase. Finally, dephospho-CoA is phosphorylated using ATP to coenzyme A by the enzyme dephosphocoenzyme A kinase. CoA undergoes dephosphorylation, catalyzed by lysosomal acid phosphatasae to dephospho-CoA, followed by pyrophosphatase action to release 4’-phosphotantetheine and 5’AMP. Red blood cells contain pantothenic acid, pantetheine 4’-phosophate and pantetheine.


Caffeine Metabolism,Metabolic

Caffeine is obtained from diet including coffee and other beverages and is absorbed in the stomach and small intestine. In the liver, the cytochrome P450 oxidase enzyme system and specifically CYP1A2 metabolizes caffeine into paraxanthine to increase lipolysis and increase free fatty acids and glycerol levels in the blood, theobromine to dilate blood vessels and increase urine volume and theophylline which relaxes bronchi smooth muscles. In the lysosome, these metabolites undergo further metabolism into methyluric acids before being excreted in the urine. There is genetic variability in the metabolism of caffeine due to the polymorphism of CYP1A2. This variability can affect the pharmacokinetic and pharmacodynamic properties of caffeine and may affect an individual's consumption.


Selenoamino Acid Metabolism,Metabolic

Selenoamino acids include selenocysteine, selenohomocysteine and selenomethionine, amino acids containing a selenium in place of a sulfur. Selenium has important biological functions but may be toxic at high doses. It is believed its toxicity arises from its induction of oxidative stress. Many selenoproteins are antioxidants. Due to its antioxidant effects selenium has become an of interest supplement to prevent diseases and cancers. Selenium and sulfur are very similar chemically, thus sulfur metabolism enzymes will act on selenium as well to form selenoamino acids which then may replace other amino acids  in protein synthesis.


Oxidation of Branched-Chain Fatty Acids,Metabolic

Fatty acid degradation in most organisms occurs primarily via the beta-oxidation cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes, whereas plants and most fungi harbor the beta-oxidation cycle only in the peroxisomes. Although the fatty acid oxidation scheme works neatly for even- numbered chain lengths, it can’t work completely for fatty acids that contain an odd number of carbons or branched chain fatty acids such as phytanic acid. Beta-oxidation of these compounds leads to propionyl-CoA and acetyl-CoA, rather than to two acetyl-CoA at the final step. The propionyl-CoA is not a substrate for the TCA cycle or other simple pathways. For example, phytanic acid, found in animal milk, can’t be oxidized directly by beta-oxidation because the addition of water is a problem at the branched beta-carbon. The first step in the digestion of this compound is the oxidation of the carbon by molecular oxygen. Then the original carboxyl group is removed as CO2, leaving a shorter chain. This chain can now be accommodated by the beta-oxidation reactions, because the new beta-carbon now lacks a methyl group. In mitochondria, the beta-oxidation pathway includes four reactions that occur in repeating cycles with each fatty acid molecule. In each cycle, a fatty acid is progressively shortened by two carbons as it is oxidized and its energy captured by the reduced energy carriers NADH and FADH2. At the end of each cycle of four reactions, one acetyl-CoA two-carbon unit is released from the end of the fatty acid, which then goes through another round of beta-oxidation, continuing to oxidize and shorten even-chain fatty acids until they are entirely converted to acetyl-CoA. The acetyl-CoA generated in beta-oxidation enters the TCA cycle, where it is further oxidized to CO2, producing more reduced energy carriers, NADH and FADH2. These carriers produced in the TCA cycle, along with those produced directly in beta-oxidation, transfer their energy to the electron transport chain where they drive the creation of the proton gradient that supports mitochondrial ATP production. Another destination of acetyl-CoA is the production of ketone bodies by the liver that are transported to tissues like the heart and brain for energy.


Pentose Phosphate Pathway,Metabolic

The pentose phosphate pathway—also referred to in the literature as the phosphogluconate pathway, the hexose monophosphate shunt, or the pentose phosphate shunt—is involved in the generation of NADPH as well as pentose sugars. Of the total cytoplasmic NADPH used in biosynthetic reactions, a significant proportion of it is generated through the pentose phosphate pathway. Ribose 5-phosphate is also another essential product generated by this pathway which is employed in nucleotide synthesis. The pentose phosphate pathway is also involved in the digestive process as the products of nucleic acid catabolism can be metabolized through the pathway (pentose sugars are usually yielded in the breakdown) while the carbon backbones of dietary carbohydrates can be converted into glycolytic/gluconeogenic intermediates. The pentose phosphate pathway is interconnected to the glycolysis pathway through the shared use of three intermediates: glucose 6-phosphate, glyceraldehyde 3-phosphate, and fructose 6-phosphate.The pathway can be described as eight distinct reactions (see below) and is separated into an oxidative phase and a non-oxidative phase. Reactions 1-3 form the oxidative phase and generate NADPH and pentose 5-phosphate. Reactions 4-8 form the non-oxidative phase and converts pentose 5-phosphate into other pentose sugars such as ribose 5-phosphate, but generates no NADPH. The eight reactions are as follows: reaction 1 converts glucose 6-phosphate into D-glucono-1,5-lactone 6-phosphate with NADPH formation; reaction 2 converts D-glucono-1,5-lactone 6-phosphate into 6-phospho-D-gluconate; reaction 3 converts 6-phospho-D-gluconate into ribulose 5-phosphate with NADPH formation; reaction 4 converts ribulose 5-phosphate into xylulose 5-phosphate; reaction 5 converts ribulose 5-phosphate into ribose 5-phosphate; reaction 6 rearranges ribose 5-phosphate and xylulose 5-phosphate to form sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate; reaction 7 rearranges sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate; and reaction 8 rearranges xylulose 5-phosphate and erythrose 4-phosphate to form glyceraldehyde 3-phosphate and fructose-6-phosphate.


Methionine Metabolism,Metabolic

Methionine metabolism in mammals consists of 2 pathways, the methionine cycle and the transsulfuration sequence. These pathways share 3 common reactions with both including the conversion of methionine to S-adenosylmethionine (SAM),the utilization of SAM in diverse transmethylation reactions yielding a methylated product plus S-adenosylhomocysteine, and the cleavage of S-adenosylhomocysteine to yield homocysteine and adenosine. The transulfuration reactions that produce cysteine from homocysteine and serine also produce α-ketobutyrate, the latter being converted first to propionyl-CoA and then via a 3-step process to succinyl-CoA. Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine. If both amino acids are present in adequate quantities, SAM accumulates and is a positive effector on cystathionine synthase, encouraging the production of cysteine and α-ketobutyrate (both of which are glucogenic). However, if methionine is scarce, SAM will form only in small quantities, thus limiting cystathionine synthase activity.


Sphingolipid Metabolism,Metabolic

The sphingolipid metabolism pathway depicted here describes the synthesis of sphingolipids which include sphingomyelins, ceramides, phosphoceramides, glucosylceramides, galactosylceramides, sulfagalactosylceramides, lactosylceramides, and various other ceramides. The core of a sphingolipid is the long-chain amino alcohol called sphingosine. Amino acylation, with a long-chain fatty acid, at the 2-carbon position of sphingosine yields a ceramide. Sphingolipids are a component of all membranes but are particularly abundant in the myelin sheath. De novo sphingolipid synthesis begins at the cytoplasmic side of the ER (endoplasmic reticulum) with the formation of 3-keto-dihydrosphingosine (also known as 3-ketosphinganine) by the enzyme known as serine palmitoyltransferase (SPT). The preferred substrates for this reaction are palmitoyl-CoA and serine. Next, 3-keto-dihydrosphingosine is reduced to form dihydrosphingosine (also known as sphinganine) via the enzyme 3-ketodihydrosphingosine reductase (KDHR), which is also known as 3-ketosphinganine reductase. Dihydrosphingosine (sphinganine) is acylated by the action of several dihydroceramide synthases (CerS) to form dihydroceramide. Dihydroceramide is then desaturated in the original palmitic portion of the lipid via dihydroceramide desaturase 1 (DES1) to form ceramide. Following the conversion to ceramide, sphingosine is released via the action of ceramidase. Sphingosine can be re-converted into a ceramide by condensation with an acyl-CoA catalyzed by the various CerS enzymes. Ceramide may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by glucosylceramide synthase (to form a glucosylceramide) or galactosylceramide synthase (to form a galactosylceramide). Additionally, it can be converted to sphingomyelin by the addition of a phosphorylcholine headgroup by sphingomyelin synthase (SMS). Sphingomyelins are the only sphingolipids that are phospholipids. Diacylglycerol is also generated via this process. Alternately, ceramide may be broken down by a ceramidase to form sphingosine. Sphingosine may be phosphorylated to form sphingosine-1-phosphate, which may, in turn, be dephosphorylated to regenerate sphingosine. Sphingolipid catabolism allows the reversion of these metabolites to ceramide. The complex glycosphingolipids are hydrolyzed to glucosylceramide and galactosylceramide. These lipids are then hydrolyzed by beta-glucosidases and beta-galactosidases to regenerate ceramide. Similarly, sphingomyelins may be broken down by sphingomyelinase to create ceramides and phosphocholine. The only route by which sphingolipids are converted into non-sphingolipids is through sphingosine-1-phosphate lyase. This forms ethanolamine phosphate and hexadecenal.


Bile Acid Biosynthesis,Metabolic

Bile acids are made in the liver by the cytochrome P450-mediated oxidation of cholesterol.  They are conjugated with taurine or the amino acid glycine, or with a sulfate or a glucuronide, and are then stored in the gallbladder.  Upon eating a meal, the contents of the gallbladder are secreted into the intestine, where bile acids serve the purpose of emulsifying dietary fats.  Bile acids serve other functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate catabolites from the liver, emulsifying lipids and fat soluble vitamins in the intestine, and aiding in the reduction of the bacteria flora found in the small intestine and biliary tract.  Bile acids formed by synthesis in the liver are termed "primary" bile acids, and those made by bacteria are termed "secondary" bile acids.  In the liver, synthesis of bile acids and bile salts is initiated with the conversion of cholesterol esters (from circulating lipoprotein particles) to cholesterol, then to 7alpha-hydroxycholesterol then to 4-cholesten-7alpha-ol-3-one.  The pathway then branches: hydroxylation of 4-cholesten-7alpha-ol-3-one to 4-cholesten-7alpha, 12alpha-diol-3-one leads ultimately to the formation of cholate, while its reduction to 5beta-cholestan-7alpha-ol-3-one leads to the formation of chenodeoxycholate.  Chenodeoxycholate has two hydroxyl groups at positions 3-alpha and 7-alpha and is a key bile acid.  Its chief drawback lies in the ability of intestinal bacteria to remove the 7-alpha hydroxyl group via dehydroxylation.  The resulting bile acid has only a 3-alpha hydroxyl group and is termed lithocholic acid.  To avoid the problems associated with the production of lithocholic acid, most mammals add a third hydroxyl group at the 12 position to chenodeoxycholic acid to create cholic acid.  In this manner, the subsequent removal of the 7-alpha hydroxyl group by intestinal bacteria will result in a less toxic, still functional dihydroxy bile acid.  In the intestine, cholic acid is dehydroxylated to form the dihydroxy bile acid deoxycholic acid.  Prior to secretion by the liver, they are conjugated with either the amino acid glycine or taurine through conversion to a Coenzyme A derivative and subsequent conjugation.  In the body, glycocholate, taurocholate, glycochenodeoxycholate, and taurochenodeoxycholate are released from hepatocytes into the bile and ultimately into the lumen of the small intestine, where they function as detergents to solubilize dietary fats.  Conjugation increases water solubility, preventing passive re-absorption once secreted into the small intestine.  As a result, the concentration of bile acids in the small intestine can stay high enough to form micelles and solubilize lipids.  Bile acids, in particular chenodeoxycholic acid (CDCA) and cholic acid (CA), can regulate the expression of genes involved in their synthesis, thereby, creating a feed-back loop.  The elucidation of this regulatory pathway came about as a consequence of the isolation of a class of receptors called the farnesoid X receptors, FXRs.  The FXRs belong to the superfamily of nuclear receptors that includes the steroid/thyroid hormone receptor family as well as the liver X receptors (LXRs), retinoid X receptors (RXRs), and the peroxisome proliferator-activated receptors (PPARs).  The FXR genes are expressed at highest levels in the intestine and liver.


D-Arginine and D-Ornithine Metabolism,Metabolic

D-Amino acids have been show to be present in high concentrations in humans and play a role in biological functions. D-Amino may have negative effects as they can be found in some bacteria or form spontaneously in certain reactions. D-Amino acid oxidase (DAAO) is one of the main enzymes that metabolize D-Amino acids via deamination. DAAO is highly specific towards D-amino acids and favours free neutral D-amino acids or those with hydrophobic, polar or aromatic groups. Acidic amino acids are not catalyze by DAOO.


Lysine Degradation,Metabolic

The degradation of L-lysine happens in liver and it is consisted of seven reactions. L-Lysine is imported into liver through low affinity cationic amino acid transporter 2 (cationic amino acid transporter 2/SLC7A2). Afterwards, L-lysine is imported into mitochondria via mitochondrial ornithine transporter 2.  L-Lysine can also be obtained from biotin metabolism. L-Lysine and oxoglutaric acid will be combined to form saccharopine by facilitation of mitochondrial alpha-aminoadipic semialdehyde synthase, and then, mitochondrial alpha-aminoadipic semialdehyde synthase will further breaks saccharopine down to allysine and glutamic acid. Allysine will be degraded to form aminoadipic acid through alpha-aminoadipic semialdehyde dehydrogenase. Oxoadipic acid is formed from catalyzation of mitochondrial kynurenine/alpha-aminoadipate aminotransferase on aminoadipic acid. Oxoadipic acid will be further catalyzed to form glutaryl-CoA, and glutaryl-CoA converts to crotonoyl-CoA, and crotonoyl-CoA transformed to 3-hydroxybutyryl-CoA. 3-Hydroxybutyryl-CoA will form Acetyl-CoA as the final product through the intermediate compound: acetoacetyl-CoA. Acetyl-CoA will undergo citric acid cycle metabolism. Carnitine is another key byproduct of lysine metabolism (not shown in this pathway).


Glycerolipid Metabolism,Metabolic

The glycerolipid metabolism pathway describes the synthesis of glycerolipids such as monoacylglycerols (MAGs), diacylglycerols (DAGs), triacylglycerols (TAGs), phosphatidic acids (PAs), and lysophosphatidic acids (LPAs). The process begins with cytoplasmic 3-phosphoglyceric acid (a product of glycolysis). This molecule is dephosphorylated via the enzyme glycerate kinase to produce glyceric acid. Glyceric acid is then transformed to glycerol (via the action of aldehyde dehydrogenase and aldose reductase). The free, cytoplasmic glycerol can then be phosphorylated to glycerol-3-phosphate through the action of glycerol kinase.  Glycerol-3-phosphate can then enter the endoplasmic reticulum where glycerol-3-phosphate acyltransferase (GPAT) may combine various acyl-CoA moieties (which donate acyl groups) to form lysophosphatidic (LPA) or phosphatidic acid (PA).  The resulting phosphatidic acids can be dephosphorylated via lipid phosphate phosphohydrolase (also known as phosphatidate phosphatase) to produce diacylglycerols (DAGs). The resulting DAGs can be converted into triacylglycerols (TAGs) via the addition of another acyl group (contributed via acyl-CoA) and the action of 1-acyl-sn-glycerol-3-phosphate acyltransferase. Extracellularly, the triacylglycerols (TAGs) can be converted to monoacylglycerols (MAGs) through the action of hepatic triacylglycerol lipase. In addition to this cytoplasmic route of glycerolipid synthesis, another route via mitochondrial synthesis also exists.  This route begins with glycerol-3-phosphate, which can be either derived from dihydroxyacetone phosphate (DHAP), a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells) or from glycerol itself. Glycerol-3-phosphate in the mitochondria is first acylated via acyl-coenzyme A (acyl-CoA) through the action of mitochondrial glycerol-3-phosphate acyltransferase to form lysophosphatidic acid (LPA). Once synthesized, lysophosphatidic acid is then acylated with another molecule of acyl-CoA via the action of 1-acyl-sn-glycerol-3-phosphate acetyltransferase to yield phosphatidic acid. Phosphatidic acid is then dephosphorylated to form diacylglycerol. Specifically, diacylglycerol is formed by the action of phosphatidate phosphatase (also known as lipid phosphate phosphohydrolase) on phosphatidic acid coupled with the release of a phosphate. The phosphatase exists as 3 isozymes. Diacylglycerol is a precursor to triacylglycerol (triglyceride), which is formed in the addition of a third fatty acid to the diacylglycerol by the action of diglyceride acyltransferase. Since diacylglycerol is synthesized via phosphatidic acid, it will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position. When the body uses stored fat as a source of energy, glycerol and fatty acids are released into the bloodstream. Fatty acids, stored as triglycerides in humans, are an important and a particularly rich source of energy. The energy yield from a gram of fatty acids is approximately 9 kcal/g (39 kJ/g), compared to 4 kcal/g (17 kJ/g) for carbohydrates. Since the hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively anhydrous (water-free) environment. Fatty acids can hold more than six times the amount of energy than sugars on a weight basis. In other words, if you relied on sugars or carbohydrates to store energy, then you would need to carry 67.5 lb (31 kg) of glycogen to have the energy equivalent to 10 lb (5 kg) of fat.