|CAS number||, (L-isomer)|
|Jmol-3D images||Image 1|
|Molar mass||135.18 g/mol|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Homocysteine [IPA: ˌhəʊməʊˈsɪstiːn] is a non-protein 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. Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins.
While detection of high levels of homocysteine has been linked to cardiovascular disease, lowering homocysteine levels may not improve outcomes.
A high level of homocysteine makes a person more prone to endothelial injury, which leads to vascular inflammation, which in turn may lead to atherogenesis, which can result in ischemic injury. Hyperhomocysteinemia is therefore a possible risk factor for coronary artery disease. Coronary artery disease occurs when an atherosclerosis leads to occlusion of the lumina of the coronary arteries. These arteries supply the heart with oxygenated blood.
Hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks and strokes, though it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions. It can cause miscarriage and/or pre-eclampsia in pregnant women, and can lead to birth defects.
Homocysteine exists at neutral pH values as a zwitterion.
Biosynthesis and biochemical roles
Homocysteine is not obtained from the diet. Instead, it is biosynthesized from methionine 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). SAM then transfers the methyl group to an acceptor molecule, (i.e., 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.
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.
Common levels in Western populations are 10 to 12, and levels of 20 μmol/L are found in populations with low B-vitamin intakes or in the older elderly (e.g., Rotterdam, Framingham). Women have 10-15% less homocysteine during their reproductive decades than men, which may help explain the fact they suffer myocardial infarction (heart attacks) on average 10 to 15 years later than men. However, this phenomenon is more readily explained by higher levels of endogenous estrogen, which exerts a cardioprotective effect.
|Sex||Age||Lower limit||Upper limit||Unit||Elevated||Therapeutic target|
|Female||12–19 years||3.3||7.2||μmol/L||> 10.4 μmol/L
> 140 μg/dl
|< 6.3 μmol/L
< 85 μg/dL
|Male||12–19 years||4.3||9.9||μmol/L||> 11.4 μmol/L
> 150 μg/dL
The ranges above are provided as examples only; test results should always be interpreted using the range provided by the laboratory that produced the result.
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 is also found to be associated with microalbuminuria which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction.
- Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G (2009). "Homocysteine lowering interventions for preventing cardiovascular events". In Martí-Carvajal, Arturo J. Cochrane Database Syst Rev (4): CD006612. doi:10.1002/14651858.CD006612.pub2. PMID 19821378.
- Boudi, Brian F. "Noncoronary Atherosclerosis". Medscape.
- Selhub, J. (1999). "Homocysteine metabolism". Annual Review of Nutrition 19: 217–246. doi:10.1146/annurev.nutr.19.1.217. PMID 10448523.
- Champe, PC and Harvey, RA. "Biochemistry. Lippincott's Illustrated Reviews" 4th ed. Lippincott Williams and Wilkins, 2008
- Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.
- Sibrian-Vazquez M, Escobedo JO, Lim S, Samoei GK, Strongin RM (January 2010). "Homocystamides promote free-radical and oxidative damage to proteins". Proc. Natl. Acad. Sci. U.S.A. 107 (2): 551–4. doi:10.1073/pnas.0909737107. PMC 2818928. PMID 20080717.
- Agnati, LF; Ferré, S; Genedani, S; Leo, G; Guidolin, D; Filaferro, M; Carriba, P; Casadó, V; Lluis, C; Franco, R; Woods, AS; Fuxe, K (Nov 2006). "Allosteric modulation of dopamine D2 receptors by homocysteine.". Journal of proteome research 5 (11): 3077–83. doi:10.1021/pr0601382. PMID 17081059.
- Nygård, O; Vollset, SE; Refsum, H; Stensvold, I; Tverdal, A; Nordrehaug, JE; Ueland, M; Kvåle, G (Nov 15, 1995). "Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study.". JAMA: the Journal of the American Medical Association 274 (19): 1526–33. doi:10.1001/jama.274.19.1526. PMID 7474221.
- Refsum, H; Nurk, E; Smith, AD; Ueland, PM; Gjesdal, CG; Bjelland, I; Tverdal, A; Tell, GS; Nygård, O; Vollset, SE (June 2006). "The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease.". The Journal of nutrition 136 (6 Suppl): 1731S–1740S. PMID 16702348.
- The Doctor's Doctor: Homocysteine
- Adëeva Nutritionals Canada > Optimal blood test values Retrieved on July 9, 2009
- Derived from molar values using molar massof 135 g/mol
- Jager, A; Kostense, PJ; Nijpels, G; Dekker, JM; Heine, RJ; Bouter, LM; Donker, AJ; Stehouwer, CD (Jan 2001). "Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study.". Arteriosclerosis, thrombosis, and vascular biology 21 (1): 74–81. doi:10.1161/01.ATV.21.1.74. PMID 11145936.
- Homocysteine MS Spectrum
- Homocysteine at Lab Tests Online
- Homocysteine: analyte monograph - The Association for Clinical Biochemistry and Laboratory Medicine
- Prof. David Spence on homocysteine levels, kidney damage, and cardiovascular disease, The Health Report, Radio National, 24 May 2010