Phosphocreatine and genistein supplementation attenuate plasma homocysteine concentrations in rats

Abstract

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. S‐adenosylmethionine (SAM) is the methyl group donor for most biological methylations. The product of this reaction, S‐adenosylhomocysteine, is converted to homocysteine (Hcy), which is remethylated back to methionine or irreversibly catabolized. Thus, Hcy pools reflect a balance between production and metabolism. Biosynthesis of phosphocreatine (PCr) from guanidinoacetate (GAA) is a transmethylation reaction that requires SAM‐derived methyl groups, contributing significantly to Hcy production. Therefore, dietary supplementation with PCr should decrease the demand on SAM for GAA synthesis. The isolflavone, genistein (G), may promote homeostatic methyl group metabolism. However, mechanisms underlying the effects of G are not well understood. We examined the effects of PCr and G supplementation on elevated Hcy during moderate folate deficiency. Half of the rats received a FD diet for 5 and ½ wk, followed by supplementation with either PCr (4g/kg/diet) or G (300mg/kg/diet) for 10 d. As expected, FD increased total plasma Hcy concentrations by 95%. PCr significantly reduced Hcy during FD (p = 0.049). However, Hcy was attenuated in all control and FD groups receiving PCr and G. Taken together, PCr and G may represent a viable dietary strategy to reduce plasma Hcy.