Nutritional regulation of homocysteine: effects of drugs.
Homocysteine plays a critical regulation role at the intersection of two metabolic pathways: remethylation and transsulfuration. Both are nutritionally regulated per se, and this issue constitutes the main goal of the present short review. In addition, several factors (i.e., drugs) may change the nutritional modulation, altering the normal functioning of the methionine/methylation cycle. The metabolism of a substrate is closely linked to that of it cofactors: in the case of homocysteine, there are three vitamins acting as cofactors or coenzymes: B6, B12 and folate. Vitamin B6 is involved in the formation of cystathionine from homocysteine (transsulfuration pathway). It is also critical for the formation of 5,10-methylentetrahydrofolate from tetrahydrofolate (folic acid derivatives), and therefore is closely related to the metabolism of folate. The latter is in conjunction with vitamin B12 involved in the remethylation of homocysteine to methionine. This reaction is B12-dependent. Different animal and human studies have proved the existence of a relation between vitamin status and homocysteine. Other dietary components as methionine content, riboflavin, alcohol or coffee consumption are being investigated in relation to homocysteine concentration. Drugs may interfere with the utilization of nutrients. This fact may be of special importance for vitamins (i.e., folate). Administration of drugs in populations with adequate vitamin intake is not usually a problem, but the existence of risk groups (the elderly, adolescents, smokers, dieters, etc.) may lead to specific vitamin deficiencies which may lead to elevated homocysteine. The case of folate is analysed since this vitamin shows the most reported number of interactions with drugs.
Varela-Moreiras
G
G
Facultad de CC, Experimentales y de la Salud, Universidad San Pablo-CEU, Urb. Montepríncipe, Boadilla del Monte, Madrid, Spain. gvarela@ceu.es
D000082:Acetaminophen / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*; D025101:Vitamin B 6 / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D005493:Folic Acid Antagonists; D006710:Homocysteine; D000082:Acetaminophen; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12; D008727:Methotrexate