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Homocysteine

|Section2={{Chembox Properties | Formula = C4H9NO2S | MolarMass = 135.18 g/mol | Appearance = White crystalline powder | Density = | MeltingPtC = 234-235 | MeltingPt_ref = | MeltingPt_notes = (decomposes) | BoilingPt = | Solubility = soluble | LogP = -2.56 | pKa = 2.25 }} |Section7={{Chembox Hazards | ExternalSDS = | GHSPictograms = | GHSSignalWord = Warning | HPhrases = | PPhrases = }} }} Homocysteine 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 certain B-vitamins. A high level of homocysteine in the blood ( hyperhomocysteinemia) makes a person more prone to endothelial cell injury, which leads to inflammation in the blood vessels, 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 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, though it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions. Hyperhomoscyteinemia has also been associated with early pregnancy loss and with neural tube defects.van der Put NJ et al Folate, Homocysteine and Neural Tube Defects: An Overview Exp Biol Med (Maywood) April 2001 vol. 226 no. 4 243-270

Structure

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, (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.Champe, PC and Harvey, RA. "Biochemistry. Lippincott's Illustrated Reviews" 4th ed. Lippincott Williams and Wilkins, 2008

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.Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. .

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.

Homocysteine levels

Homocysteine levels are typically 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 older elderly (e.g., Rotterdam, Framingham). 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.

Elevated homocysteine

Abnormally high levels of homocysteine in the serum, above 15 µmol/L, are a medical condition called hyperhomocysteinemia.http://www.merckmanuals.com/professional/hematology-and-oncology/thrombotic-disorders/hyperhomocysteinemia#v12779073 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. Additionally, elevated homocysteine is found in megaloblastic anemia.

References

External links

"green air" © 2007 - Ingo Malchow, Webdesign Neustrelitz
This article based upon the http://en.wikipedia.org/wiki/Homocysteine, the free encyclopaedia Wikipedia and is licensed under the GNU Free Documentation License.
Further informations available on the list of authors and history: http://en.wikipedia.org/w/index.php?title=Homocysteine&action=history
presented by: Ingo Malchow, Mirower Bogen 22, 17235 Neustrelitz, Germany