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. Hyperhomocysteinemia has also been associated with early pregnancy loss and with neural tube defects.
Zwitterionic form of (S)-homocysteine (left) and (R)-homocysteine (right)
Homocysteine exists at neutral pH values as a zwitterion.
Biosynthesis and biochemical roles
Two of homocysteine's main biochemical roles. (Homocysteine is seen in the left middle of the image.) It can be synthesized from methionine and then converted back to methionine via the SAM cycle or used to create cysteine and alpha-ketobutyrate.
Mammals biosynthesize the amino acid cysteine via homocysteine. Cystathionine ?-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (vitamin B6) as a cofactor. Cystathionine ?-lyase then converts this double amino acid to cysteine, ammonia, and ?-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.
Homocysteine levels are typically higher in men than women, and increase with age.
Common levels in Western populations are 10 to 12 ?mol/L, and levels of 20 ?mol/L are found in populations with low B-vitamin intakes or in the elderly (e.g., Rotterdam, Framingham).
It is decreased with methyl folate trapping, where it is accompanied by decreased methylmalonic acid, increased folate and a decrease in formiminoglutamic acid. This is the opposite of MTHFR C677T mutations, which result in an increase in homocysteine.
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. Vitamin B12 deficiency, when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well.
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