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Possible mechanisms of homocysteine toxicity
Alessandra F Perna1, Diego Ingrosso, Cinzia Lombardi
1First Division of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples, Italy. alessandra.perna@unina2.it
Insights
Hyperhomocysteinemia, elevated homocysteine in the blood, is linked to cardiovascular disease. In chronic renal failure, this condition is common and may stem from several toxic mechanisms.
Area of Science:
- Biochemistry
- Nephrology
- Cardiovascular Science
Background:
- Hyperhomocysteinemia is a known cardiovascular disease risk factor in the general population.
- In chronic renal failure (CRF), reduced glomerular filtration rate (GFR) leads to elevated plasma homocysteine levels.
- The majority of patients with uremia exhibit hyperhomocysteinemia.
Purpose of the Study:
- To review the potential mechanisms underlying homocysteine toxicity.
- To explore how homocysteine contributes to adverse health outcomes, particularly in the context of chronic kidney disease.
Main Methods:
- Literature review of homocysteine toxicity mechanisms.
- Analysis of biochemical pathways involving homocysteine metabolism and its effects.
- Examination of studies related to hyperhomocysteinemia in chronic renal failure and uremia.
Main Results:
- Homocysteine exerts toxicity through several pathways, including oxidative stress via reactive oxygen species production.
- Homocysteine can bind to nitric oxide, impairing its function.
- It leads to the formation of homocysteinylated/acylated proteins.
- Accumulation of S-adenosyl-homocysteine inhibits crucial transmethylation reactions.
Conclusions:
- Methyltransferase inhibition by homocysteine metabolites is confirmed in CRF and uremia.
- These biochemical disruptions can lead to significant functional consequences, contributing to disease pathology.
- Understanding these mechanisms is vital for managing cardiovascular risk in patients with kidney disease.
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.