Possible mechanisms of homocysteine toxicity.
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.
Perna
Alessandra F
AF
First Division of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples, Italy. alessandra.perna@unina2.it
Ingrosso
Diego
D
Lombardi
Cinzia
C
Acanfora
Filomena
F
Satta
Ersilia
E
Cesare
Concetta Maria
CM
Violetti
Eleonora
E
Romano
Maria Maddalena
MM
De Santo
Natale G
NG
D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000378:metabolism*; D014118:Toxins, Biological / Q000378:metabolism*; D014511:Uremia / Q000150:complications / Q000378:metabolism*
D014118:Toxins, Biological; D006710:Homocysteine