title: Possible mechanisms of homocysteine toxicity.
abstract: Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population. In chronic renal failure (CRF), plasma homocysteine levels rise when the glomerular filtration rate (GFR) is reduced 50%, and in uremia the majority of patients are hyperhomocysteinemic. The purpose of this study was to review possible mechanisms of homocysteine toxicity. Homocysteine, a sulfur amino acid found in blood in micromolar concentrations, can have toxic effects through a handful of general possible mechanisms. These mechanisms include oxidative stress (through the production of reactive oxygen species), binding to nitric oxide, production of homocysteinylated/acylated proteins, and accumulation of its precursor, S-adenosyl-homocysteine, a potent inhibitor of transmethylation reactions. Methyltransferase inhibition actually occurs in CRF and in uremia, and can have several functional consequences.
authors.affiliation: First Division of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples, Italy. alessandra.perna@unina2.it
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lombardi
authors.forename: Filomena
authors.initials: F
authors.lastname: Acanfora
authors.forename: Ersilia
authors.initials: E
authors.lastname: Satta
authors.forename: Concetta Maria
authors.initials: CM
authors.lastname: Cesare
authors.forename: Eleonora
authors.initials: E
authors.lastname: Violetti
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Romano
authors.forename: Natale G
authors.initials: NG
authors.lastname: De Santo
mesh_terms: D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000378:metabolism*; D014118:Toxins, Biological / Q000378:metabolism*; D014511:Uremia / Q000150:complications / Q000378:metabolism*
chemical_list: D014118:Toxins, Biological; D006710:Homocysteine