|Systematic (IUPAC) name|
Homocysteine is a chemical compound with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the naturally-occurring amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. Alternatively, homocysteine can be derived from methionine by removing the latter's terminal Cε methyl group.
Organic chemical properties
The "extra" (relative to cysteine) one carbon methylene group allows this molecule to form a five-membered ring, homocysteine thiolactone. The facility of this reaction precludes the formation of stable peptide bonds. In other words, a protein containing homocysteine would tend to cleave itself.
The 4 carbon homocysteine is (only) made from the 5 carbon methionine, an essential amino acid, in a multi step reaction via S-adenosyl methionine. Homocysteine can be recycled back into methionine or it can be permanently converted to cysteine via the transsulfuration pathway. Homocysteine is not obtained from the diet; it is a normal temporary and chemically reactive reaction product that can be measured in blood. Due to its high reactivity to proteins, it is almost always bound to proteins, 'thiolating' (and thus degrading) most notably the lysine and cysteine components thereof. This can permanently affect protein function. In blood, it is found bound to albumin and to hemoglobin. It affects enzymes with cysteine-containing active sites, for example, it inhibits lysyl oxidase a key enzyme in the production of collagen and elastin, two main structural proteins in artery, bone and skin.
As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of the vitamins folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin) can lead to high homocysteine levels. Supplementation with pyridoxine, folic acid, B12 or trimethylglycine (betaine) reduces the concentration of homocysteine in the bloodstream.  Increased levels of homocysteine are linked to high concentrations of endothelial asymmetric dimethylarginine.
Elevations of homocysteine also occur in the rare hereditary disease homocystinuria and in the methylene-tetrahydrofolate-reductase polymorphism genetic traits. The latter is quite common (about 10% of the world population) and it is linked to an increased incidence of thrombosis and cardiovascular disease and that occurs more often in people with above minimal levels of homocysteine (about 6 μmol/L). Common levels in Western populations are 10 to 12 and levels of 20 μmol/L are found in populations with low B-vitamin intakes (New Delhi) or in the older elderly (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.
A high level of blood serum homocysteine is a powerful risk factor for cardiovascular disease. Unfortunately, one study which attempted to decrease the risk by lowering homocysteine was not fruitful. This study was conducted on nearly 5000 Norwegian heart attack survivors who already had severe, late-stage heart disease. No study has yet been conducted in a preventative capacity, on subjects who are in a relatively good state of health.
Studies reported in 2006 have shown that giving vitamins [folic acid, B6 and B12] to reduce homocysteine levels may not quickly offer benefit, however a significant 25% reduction in stroke was found in the HOPE-2 study  even in patients mostly with existing serious arterial decline although the overall death rate was not significantly changed by the intervention in the trial. Clearly, reducing homocysteine does not quickly repair existing structural damage of the artery architecture. However, the science is strong supporting the biochemistry that homocysteine degrades and inhibits the formation of the three main structural components of the artery, collagen, elastin and the proteoglycans. Homocysteine permanently degrades cysteine [disulfide bridges] and lysine amino acid residues in proteins, gradually affecting function and structure. Simply put, homocysteine is a 'corrosive' of long-living [collagen, elastin] or life-long proteins [fibrillin]. These long-term effects are difficult to establish in clinical trials focusing on groups with existing artery decline. The main role of reducing homocysteine is likely in 'prevention' but with a slow but probable role in 'cure'. 
Elevated levels of homocysteine have been linked to increased fractures in elderly persons. Homocysteine does not appear to have any effect on bone density. Instead, it appears that homocysteine affects collagen by interfering with the cross-linking between collagen fibers and the tissues they reinforce.
Vitamin supplements could counter the effects of homocysteine on collagen. As B12 is inefficiently absorbed from food by elderly persons, they could gain a greater benefit from taking in higher doses orally or via intramuscular injection.
- Selhub, J. (1999). "Homocysteine metabolism". Annual Review of Nutrition. 19: 217&ndash, 246. PMID 10448523.
- Miller JW, Nadeau MR, Smith D and Selhub J (1994). "Vitamin B-6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats". American Journal of Clinical Nutrition. 59: 1033&ndash, 1039. PMID 8172087.
- Coen DA Stehouwer, Coen van Guldener (2001). "Homocysteine-lowering treatment: an overview". Expert Opinion on Pharmacotherapy. 2 (9): 1449&ndash, 1460. PMID 11585023.
- Legal note: Metabolite Laboratories is defending a patent as of March 2006 that may cover the mere mention or consideration of the relationship of vitamin B12 and homocysteine levels. See Crichton, Michael (March 19, 2006). "This Essay Breaks the Law". The New York Times. The New York Times Company. Retrieved 2006-03-20.
- "B vitamins do not protect hearts". BBC News. BBC. September 6, 2005. Retrieved 2006-03-20.
- "Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease". N Engl J Med. 2006. PMID 16531613 Full text PDF.
- Zoungas S, McGrath BP, Branley P, Kerr PG, Muske C, Wolfe R, Atkins RC, Nicholls K, Fraenkel M, Hutchison BG, Walker R, McNeil JJ (2006). "Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial". J Am Coll Cardiol. 47 (6): 1108–16. PMID 16545638.
- Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K (2006). "Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction". N Engl J Med. PMID 16531614 Full text PDF.
- McLean RR; et al. (2004). "Homocysteine as a predictive factor for hip fracture in older persons". New England Journal of Medicine. 350: 2042&ndash, 2049. PMID 15141042.Free text after free regitration
- van Meurs JB; et al. (2004). "Homocysteine levels and the risk of osteoporotic fracture". New England Journal of Medicine. 350: 2033&ndash, 2041. PMID 15141041.Free text after free regitration