title: Folate deprivation, the methionine cycle, and Alzheimer's disease.
abstract: Folate deficiency is associated with increase in homocysteine levels. Abnormal plasma levels of that neurotoxic nonproteinogenic amino acid is implicated in many pathological conditions including cardiovascular diseases, neural tube defects, and is now recognized as a risk factor in Alzheimer's disease (AD) dementia. Homocysteine elimination is regulated by two metabolic pathways, namely, the transmethylation and the transsulfuration pathways. Its elimination via these two metabolic pathways is modulated by folate, a member of the B-vitamin family. Folate provides, via its metabolic end product 5-methyltetrahydrofolate, a methyl group that is used to reconvert homocysteine back to methionine through the transmethylation pathway. The efficiency of folate metabolism has an impact on the availability of S-adenosylmethionine, a compound that is known to activate homocysteine flux through the transsulfuration pathway and is necessary for utilization of a downstream antioxidant called glutathione under the catalysis of glutathione S-transferase enzyme. In this review, we will explore the impact of folate deprivation on the regulation of the methionine cycle and exhaustively describe different biochemical reactions that are implicated in the regulation of homocysteine elimination and that folate deficiency influences in AD neuropathology.
authors.affiliation: University of Maryland, Baltimore, Maryland, USA.
authors.forename: Flaubert
authors.initials: F
authors.lastname: Tchantchou
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia; D008715:Methionine / Q000378:metabolism*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine