homocysteine homocysteine homocysteine /ˌhoʊmoʊˈsɪstiːn/ is a non-proteinogenic α-amino acid. it is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-ch2-). it is biosynthesized from methionine by the removal of its terminal cε methyl group. in the body, homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin b6, b9, and b12. homocysteine names iupac name 2-amino-4-sulfanylbutanoic acid identifiers cas number 454-29-5 (racemate) y6027-13-0 (l-isomer) y 3d model (jsmol) interactive image chebi chebi:17230 y chembl chembl310604 y chemspider 757 y echa infocard 100.006.567 ec number 207-222-9 kegg c05330 y pubchem cid 778 unii s7ijp4a89k (racemate) y0lvt1qz0ba (l-isomer) y inchi inchi=1s/c4h9no2s/c5-3(1-2-8)4(6)7/h3,8h,1-2,5h2,(h,6,7) ykey: fffhzydwpbmwhy-uhfffaoysa-n yinchi=1/c4h9no2s/c5-3(1-2-8)4(6)7/h3,8h,1-2,5h2,(h,6,7)key: fffhzydwpbmwhy-uhfffaoyas smiles c(cs)c(c(=o)o)n properties chemical formula c4h9no2s molar mass 135.18 g/mol appearance white crystalline powder melting point 234–235 °c (453–455 °f; 507–508 k) (decomposes) solubility in water soluble log p -2.56 acidity (pka) 2.25 hazards ghs labelling: pictograms signal word warning hazard statements h302 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references high levels of homocysteine in the blood (hyperhomocysteinemia) is regarded as a marker of cardiovascular disease, likely working through atherogenesis, which can result in ischemic injury. therefore, hyperhomocysteinemia is a possible risk factor for coronary artery disease. coronary artery disease occurs when an atherosclerotic plaque blocks blood flow to the coronary arteries, which supply the heart with oxygenated blood. hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks, and strokes, although it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions. hyperhomocysteinemia also has been associated with early-term spontaneous abortions and with neural tube defects. structure zwitterionic form of (s)-homocysteine (left) and (r)-homocysteine (right) homocysteine exists at neutral ph values as a zwitterion. biosynthesis and biochemical roles two of homocysteine's main biochemical roles - (homocysteine is seen in the left middle of the image.) it can be synthesized from methionine and then converted back to methionine via the sam cycle or used to create cysteine and alpha-ketobutyrate. homocysteine is biosynthesized naturally via a multi-step process. first, methionine receives an adenosine group from atp, a reaction catalyzed by s-adenosyl-methionine synthetase, to give s-adenosyl methionine (sam-e). sam-e then transfers the methyl group to an acceptor molecule, (e.g., norepinephrine as an acceptor during epinephrine synthesis, dna methyltransferase as an intermediate acceptor in the process of dna methylation). the adenosine is then hydrolyzed to yield l-homocysteine. l-homocysteine has two primary fates: conversion via tetrahydrofolate (thf) back into l-methionine or conversion to l-cysteine. biosynthesis of cysteine mammals biosynthesize the amino acid cysteine via homocysteine. cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. this reaction uses pyridoxine (vitamin b6) as a cofactor. cystathionine γ-lyase then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate. bacteria and plants rely on a different pathway to produce cysteine, relying on o-acetylserine. mthfr metabolism: folate cycle, methionine cycle, trans-sulfuration and hyperhomocysteinemia - 5-mthf: 5-methyltetrahydrofolate; 5,10-methyltetrahydrofolate; bax: bcl-2-associated x protein; bhmt: betaine-homocysteine s-methyltransferase; cbs: cystathionine beta synthase; cgl: cystathionine gamma-lyase; dhf: dihydrofolate (vitamin b9); dmg: dimethylglycine; dtmp: thymidine monophosphate; dump: deoxyuridine monophosphate; fad+ flavine adenine dicucleotide; fthf: 10-formyltetrahydrofolate; ms: methionine synthase; mthfr: mehtylenetetrahydrofolate reductase; sah: s-adenosyl-l-homocysteine; same: s-adenosyl-l-methionine; thf: tetrahydrofolate methionine salvage homocysteine can be recycled into methionine. this process uses n5-methyl tetrahydrofolate as the methyl donor and cobalamin (vitamin b12)-related enzymes. more detail on these enzymes can be found in the article for methionine synthase. other reactions of biochemical significance homocysteine can cyclize to give homocysteine thiolactone, a five-membered heterocycle. because of this "self-looping" reaction, homocysteine-containing peptides tend to cleave themselves by reactions generating oxidative stress. homocysteine also acts as an allosteric antagonist at dopamine d2 receptors. it has been proposed that both homocysteine and its thiolactone may have played a significant role in the appearance of life on the early earth. homocysteine levels total plasma homocysteine homocysteine levels typically are higher in men than women, and increase with age. common levels in western populations are 10 to 12 μmol/l, and levels of 20 μmol/l are found in populations with low b-vitamin intakes or in the elderly (e.g., rotterdam, framingham). it is decreased with methyl folate trapping, where it is accompanied by decreased methylmalonic acid, increased folate, and a decrease in formiminoglutamic acid. this is the opposite of mthfr c677t mutations, which result in an increase in homocysteine. blood reference ranges for homocysteine: sexagelower limitupper limitunitelevatedtherapeutic target female12–19 years3.37.2μmol/l> 10.4 μmol/l or > 140 μg/dl< 6.3 μmol/l or < 85 μg/dl 45100μg/dl >60 years4.911.6μmol/l 66160μg/dl male12–19 years4.39.9μmol/l> 11.4 μmol/l or > 150 μg/dl 60130μg/dl >60 years5.915.3μmol/l 80210μg/dl the ranges above are provided as examples only; test results always should be interpreted using the range provided by the laboratory that produced the result. elevated homocysteine main article: hyperhomocysteinemia abnormally high levels of homocysteine in the serum, above 15 μmol/l, are a medical condition called hyperhomocysteinemia. this has been claimed to be a significant risk factor for the development of a wide range of diseases, including thrombosis, neuropsychiatric illness, and fractures. it also is found to be associated with microalbuminuria, which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. vitamin b12 deficiency, when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well. typically, hyperhomocysteinemia is managed with vitamin b6, vitamin b9, and vitamin b12 supplementation. however, supplementation with these vitamins does not appear to improve cardiovascular disease outcomes.