Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism

Abstract

One-carbon metabolism is a network of interrelated biochemical reactions that involve the transfer of one-carbon groups from one compound to another. The coenzymes necessary for several of these reactions include the B-vitamins, folate, vitamin B-12, vitamin B-6 and riboflavin (vitamin B-2), whereas important intermediary compounds in this schema include methionine and choline. There has been renewed interest in one-carbon metabolism during the past several years, engendered by recent insights that indicate that modest dietary inadequacies of the abovementioned nutrients, of a degree insufficient to cause classical deficiency syndromes, can still contribute to important diseases such as neural tube defects, cardiovascular disease and cancer. Traditional means of assessing nutrient exposure with food frequency questionnaires, and nutrient status with plasma and urine vitamin assays, has some genuine validity and utility. Assessing the concentration of appropriate intermediary compounds, such as plasma homocysteine for folate and methylmalonic acid for vitamin B-12, provides further insights because they appear to add a degree of sensitivity that does not exist with the more traditional assays. There may also be value in developing measures that integrate the status of all these nutrients and express it as a functional "methylation capacity" of the individual. Plasma or tissue concentrations of S-adenosylmethionine and S-adenosylhomocysteine, and genomic DNA methylation are two potential candidates in this regard although much work is yet to be done to define the nature of these relationships.