title: Consideration of betaine and one-carbon sources of N5-methyltetrahydrofolate for use in homocystinuria and neural tube defects.
abstract: A major focus in attempts to ameliorate homocystinuria and neural tube defects is supplementation of the diet with B vitamins. The metabolic defect in these cases may be due in part to a deficiency of methyl groups. B vitamin supplementation supports the need for enzyme cofactors but cannot provide substrate in the form of methyl groups. l-Methionine is an essential amino acid and is required for protein synthesis, but it also plays a unique role in metabolism as S-adenosylmethionine, which is the primary methyl donor in metabolism. The observation that l-homocysteine, which is produced in the metabolism of l-methionine, is remethylated 2-4 times before it is destroyed is key to understanding the possibility of a methyl group deficiency. This suggests that the requirement for methyl groups (ie, S-adenosylmethionine) may be 2-4 times that for methionine in support of protein synthesis. l-Homocysteine can be remethylated to form l-methionine by betaine or N(5)-methyltetrahydrofolate. Betaine and one-carbon sources that lead to the production of N(5)-methyltetrahydrofolate and the remethylation of l-homocysteine to form l-methionine should be considered along with B vitamin supplementation in the treatment of homocystinuria and neural tube defects.
authors.affiliation: Department of Animal Sciences and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA. njbeneve@ansci.wisc.edu
authors.forename: Norlin J
authors.initials: NJ
authors.lastname: Benevenga
mesh_terms: D001622:Betaine / Q000378:metabolism / Q000627:therapeutic use*; D019587:Dietary Supplements; D005492:Folic Acid / Q000378:metabolism / Q000627:therapeutic use*; D006710:Homocysteine / Q000378:metabolism; D006712:Homocystinuria / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D009436:Neural Tube Defects / Q000188:drug therapy* / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D012436:S-Adenosylmethionine / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D014803:Vitamin B Complex / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D014803:Vitamin B Complex; D001622:Betaine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D008715:Methionine