Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Abstract

Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...

Effects of Betaine Supplementation and Choline Deficiency on Folate Deficiency-Induced Hyperhomocysteinemia in Rats

“…Another possible reason is that 20CFD, compared with 10CFD, increased or tended to increase the activities of three enzymes that participate in the metabolism of homocysteine. The third possible reason is that plasma cysteine concentration was increased in rats fed 20CFD and thereby reduced plasma homocysteine, because cysteine elicits its hypohomocysteinemic effect through the enhancement of plasma cysteine (42). In any case, the present study suggests that rats fed diets containing higher levels of casein are less susceptible to folate deficiency.…”

Hepatic Cystathionine β-Synthase Activity Does Not Increase in Response to Methionine Supplementation in Rats Fed a Low Casein Diet: Association with Plasma Homocysteine Concentrations

“…These results suggest that the hypohomocysteinemic effect of moderate and high casein diets cannot be ascribed solely to glycineϩ serine contained in casein, although these amino acids surely contribute to the prevention of methionineinduced hyperhomocysteinemia to a considerable degree. In the present study, we did not test the effect of cystine, because the cystine content of casein is very low and cystine did not exhibit a hypohomocysteinemic effect when added to methionine-supplemented diets in rats (30). We recently reported that glutamic acid, histidine, and arginine significantly suppressed methionineinduced hyperhomocysteinemia when added to a methionine-supplemented diet at a level of 2.5%, although the effects of these amino acids were far weaker than those of glycine and serine (31).…”

“…Before starting the experiments, all rats were acclimated to the facility for 5 d and given free access to water and a 25% casein diet. In the present study, seven experimental diets (A-G) differing in casein level (10,30, and 50%) and differing in methionine level together with or without glycine ϩ serine supplementation were used (Table 1). These diets were abbreviated as follows:…”

Effect of Nitrous Oxide Exposure During Surgery on the Homocysteine Concentrations of Children

“…Free serine, glycine and cysteine supplements lowered homocysteine concentrations in rodents fed either a low-protein or a high-protein diet (94)(95)(96). The lowering effect of cysteine is associated with increased plasma cysteine concentrations in rodents (97). In apparently healthy humans, concurrent intake of free cysteine and serine can attenuate the rise on postprandial homocysteine concentrations as a result of free methionine (17).…”