title: The folate cycle and disease in humans.
abstract: The prevalence of hyperhomocysteinemia in renal disease patients, its treatment by folate administration, and its aggravation by the 677 C-->T mutation of methylene-tetrahydrofolate (methylene-THF) reductase has established the folate cycle as an important factor in the pathogenesis and management of renal disease. Proper function of the folate cycle depends on normal function of involved enzymes adequate of the vitamin and its correct disposition within the body. Vital processes in folate disposition include conversion of dietary folylpolyglutamates to monoglutamates, intestinal absorption, receptor and carrier-mediated transport across cell membranes, and cellular export. Folate coenzymes are responsible for the one-carbon unit transfer in intermediary metabolism and are required for several reactions in key metabolic processes, for example of purine, pyrimidine and methionine synthesis, and glycine and serine metabolism. Methionine synthase and its recently discovered reducing protein as well as methylene tetrahydrofolate reductase are key folate enzymes in homocysteine metabolism. Deficiencies of these enzymes are important causes of severe disease in the rare remethylation defects causing homocystinuria. Knowledge of their catalytic and molecular properties is important in understanding possible causes of moderate hyperhomocysteinemia, as for example, the well-known 677 C-->T transition of methylene tetrahydrofolate reductase.
authors.affiliation: Metabolic Unit, University Children's Hospital Basel (UKBB), Basel, Switzerland. Brian.Fowler@unibas.ch
authors.forename: B
authors.initials: B
authors.lastname: Fowler
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000619:Aminohydrolases / Q000378:metabolism; D001693:Biological Transport, Active; D005492:Folic Acid / Q000378:metabolism*; D005574:Formate-Tetrahydrofolate Ligase / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D006706:Homeostasis; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000378:metabolism; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009097:Multienzyme Complexes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011099:Polyglutamic Acid / Q000378:metabolism; D011685:Purine Nucleotides / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D011685:Purine Nucleotides; D013763:Tetrahydrofolates; D006710:Homocysteine; C013123:5,10-methylenetetrahydrofolic acid; D011099:Polyglutamic Acid; D012694:Serine; D006639:Histidine; C021836:formyl-methenyl-methylenetetrahydrofolate synthetase; D005492:Folic Acid; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D000619:Aminohydrolases; D005574:Formate-Tetrahydrofolate Ligase