Methods in assessing homocysteine metabolism.
Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine. High blood levels of homocysteine result in far-reaching biochemical and life-threatening consequences. Homocysteine exists at a critical biochemical intersection in the methionine cycle between S-adenosylmethionine, the ubiquitous methyl donor, and vitamins B(12) and folic acid. Indirect and direct vascular damage can be caused by homocysteine, a putative atherothrombotic risk factor. Homocysteine has been associated with vascular disease, particularly in subjects with significant carotid stenosis. Increasing evidence for a connection between homocysteine metabolism and cognitive function is surfacing, and this includes from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. In the elderly population increase in homocysteine is commonly seen due to significant deficiencies in cobalamin (B(12)), folate and vitamin B(6.) All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, rendering vascular structures more susceptible to damage. Decreasing plasma homocysteine, by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. The current methods of evaluation of homocysteine metabolism include assessment of cobalamin (B(12)) and folate and vitamin B(6) status and screening for mutations in the genes encoding the enzymes of metabolism. An accurate method for the estimation of plasma and tissue levels of homocysteine would contribute greatly to a proper understanding of the metabolism. In the current review emphasis will be on the estimation of homocysteine, and evaluation of one of the common mutations encountered in the metabolism of this amino acid.
Murthy
Subramanyam N
SN
Department of Medicine, Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, Louisiana.
Matta
Anil S
AS
Mondal
Debasis
D
McNamara
Dennis B
DB