Article: Homocysteine

Homocysteine
Systematic name	(2S)-2-amino-4-sulfanyl-butanoic acid
Abbreviations	Hcy
Chemical formula	C4H9NO2S
Molecular mass	135.186 g mol-1
CAS number	(L) 454-29-5 (DL) 454-29-5
PubChem	CID 91552 from PubChem (L)
SMILES	C(CS)C(C(=O)O)N
Complete data

Homocysteine is a variant of the amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH₂-) group before the thiol (-SH) group.

Chemistry

Homocysteine's extra methylene group brings the thiol group closer to the carboxyl group, allowing it to chemically react to form a five-membered ring. This occurs at the point where the amino acids normally join to their neighbours in a peptide bond. Homocysteine is therefore unsuitable for incorporating into proteins, because a protein containing homocysteine would cleave itself.

Homocysteine is formed from S-adenosyl methionine by a two step reaction pathway. It can be converted back to methionine, or converted to cysteine or taurine via the transsulfuration pathway. Although homocysteine can be converted back to methionine, there is no indication that dietary homocysteine contributes any methionine nutritionally to humans.^[1]

Elevated homocysteine

As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of the vitamins folic acid, pyridoxine (B₆), or B₁₂ can lead to high homocysteine levels.^[2] Supplementation with pyridoxine, folic acid, B₁₂ or trimethylglycine (betaine) reduces the concentration of homocysteine in the bloodstream.^{[3] [4]}. 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 methyl-tetrahydrofolate-reductase deficiency. The latter is quite common and usually goes unnoticed, although there are reports that thrombosis and cardiovascular disease occurs more often in people with elevated homocysteine.

Homocysteine appears to be downregulated by high concentrations of polyphenol antioxidants^{[citation needed]} , chemicals which are known to provide certain health benefits to the cardiovascular system and immune system. These chemicals are known to down-regulate the formation of reactive oxygen species, key chemicals in cardiovascular disease.

Cardiovascular risks

A high level of blood serum homocysteine is considered to be a marker of potential cardiovascular (risk factor for heart attack and stroke) disease. A current area of research is whether high serum homocysteine itself is a problem or merely an indicator of existing problems.^[5]

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^{[citation needed]} even in patients mostly with existing serious arterial decline. 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 3 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 focussing 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'. ^[6][7][8]

Bone weakness

Elevated levels of homocysteine have been linked to increased fractures in elderly persons.^[9][10] 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 vitamin supplements.