Homocysteine effect on protein degradation rates

Objectives To show the effect of homocysteine (Hcy) on the degradation rates of proteins. Design and methods Degradation rates of short-lived proteins in neutrophils were measured in in vivo human model of elevated plasma Hcy and lower vitamin status and in animal model of Hcy added in vitro to rat neutrophils. Results In the human study, we found significant coefficients of correlation between plasma total homocysteine (tHcy) and the degradation rates of 21 protein fractions. In the animal model, Hcy significantly increased degradation rates of 57 protein fractions. Conclusions The increase in protein degradation rates, induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy detrimental effects. Hcy may amplify the specific effect of cellular solutes on protein conformation, thereby monitor protein degradation rates to control enzyme activity. Consequently, the cell may lose its ability to maintain an efficient control of some crucial metabolic pathways, possibly leading to atherogenesis