Homocysteine
From Wikipedia, the free encyclopedia
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Homocysteine |
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| Systematic (IUPAC) name | |
| (2S)-2-amino-4-sulfanyl-butanoic acid | |
| Identifiers | |
| CAS number | 454-29-5 |
| PubChem | 91552 |
| Chemical data | |
| Formula | C4H9NO2S |
| Mol. weight | 135.186 |
| SMILES | C(CS)C(C(=O)O)N |
| Complete data | |
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.
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[edit] Organic chemical properties
The "extra" (relative to cysteine) 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.
Homocysteine is formed from S-adenosyl methionine by a two step reaction. 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]
[edit] 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 methylene-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. Direct generation of reactive oxygen species by homocysteine may also contribute to biological damage [1] [2].
[edit] 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 [6] 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'. [6][7][8]
[edit] 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 in higher doses orally or via intramuscular injection.
[edit] References
- ^ Selhub, J. (1999). "Homocysteine metabolism.". Annual Review of Nutrition 19: 217–246. 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: 1033–1039. PMID 8172087.
- ^ Coen DA Stehouwer, Coen van Guldener (2001). "Homocysteine-lowering treatment: an overview". Expert Opinion on Pharmacotherapy 2 (9): 1449–1460. 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. "This Essay Breaks the Law", The New York Times, The New York Times Company, March 19, 2006. Retrieved on 2006-03-20.
- ^ "B vitamins do not protect hearts", BBC News, BBC, September 6, 2005. Retrieved on 2006-03-20.
- ^ a b (2006) "Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease". N Engl J Med. 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: 2042–2049. 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: 2033–2041. PMID 15141041. Free text after free regitration
