Effects of Various Amino Acids on Methionine-Induced Hyperhomocysteinemia in Rats

Fukada, Shin-ichiro; Morita, Tatsuya; Sugiyama, Kimio

doi:10.1271/bbb.70833

Cited by 6 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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). Hence, the possibility that some amino acids other than glycine and serine also contribute to the effect of moderate and high casein diets cannot be excluded.…”

Section: Discussionmentioning

confidence: 76%

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

Ohuchi

Morita

Mori

et al. 2009

J Nutr Sci Vitaminol

Self Cite

View full text Add to dashboard Cite

Summary To elucidate the mechanism by which moderate and high protein diets fail to increase plasma homocysteine concentration despite dietary methionine levels being higher, rats were fed diets with graded levels (10, 30, and 50%) of casein or low casein diets supplemented with methionine at levels of 0.5 and 1.0% together with or without glycine ϩ serine, which corresponded to moderate and high casein diets with respect to these amino acids, for 14 d. The plasma homocysteine concentration significantly decreased with an increase in dietary casein level, whereas it significantly increased with an increase in dietary methionine level when the low casein diet was supplemented with methionine. Supplementation with glycine ϩ serine significantly suppressed the elevation of plasma homocysteine concentration due to methionine supplementation, but it could not decrease plasma homocysteine concentration to the levels in rats fed corresponding casein diets. Increased concentrations of hepatic S -adenosylhomocysteine and homocysteine due to methionine supplementation were also significantly suppressed by glycine ϩ serine. The activity of hepatic cystathionine ␤ -synthase (CBS) did not increase in response to methionine supplementation, while it significantly increased with an increase in dietary casein level. In contrast, the activity of hepatic betaine-homocysteine S -methyltransferase (BHMT) significantly increased with increase in both dietary casein level and dietary methionine level. Hepatic levels of mRNA for CBS and BHMT were parallel to the enzyme activities. The results suggest that, in contrast to methionine-supplemented low casein diets, moderate and high casein diets avoid increasing plasma homocysteine concentration through dual mechanisms, greater supply of glycine ϩ serine and an increase in CBS activity. Key Words dietary methionine level, dietary casein level, plasma homocysteine, cystathionine ␤ -synthase, betaine-homocysteine S -methyltransferase Homocysteine is known to be one of the intermediates of methionine metabolism ( Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration might be an independent risk factor for cardiovascular disease ( 2 -4 ). The plasma homocysteine concentration is affected by various factors such as genetic, nutritional, physiological, clinical, and lifestyle factors. Of these factors, genetic and nutritional factors are thought to have a greater influence on the plasma homocysteine concentration. For instance, deficiencies of folate, vitamin B12, and vitamin B6 cause hyperhomocysteinemia, since these vitamins participate in the metabolism of homocysteine. The relationship between protein intake and plasma homocysteine concentration is one of the subjects attracting much attention, since the intake of protein is usually associated with the intake of methionine, the sole precursor of homocysteine. In humans, high protein diets increased postprandial plasma homocysteine concentration ( 5 -7 ), while high protein diets did not al...

show abstract

Section: Discussionmentioning

confidence: 76%

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

Ohuchi

Morita

Mori

et al. 2009

J Nutr Sci Vitaminol

Self Cite

View full text Add to dashboard Cite

show abstract

“…The discrepancy between the results of the study by Verhoef et al (10) and the results of the present study appears to be due to different experimental conditions, e.g., single ingestion vs. successive feeding of diets. On the other hand, we recently reported that cysteine significantly increased plasma homocysteine concentration in rats when supplemented to a 25% caseinϩ1% methionine diet at a high (2.5%) level (13), suggesting that a combination of high levels of methionine and cysteine rather leads to an elevation of plasma homocysteine concentration. There are several explanations for the hypohomocysteinemic effect of NAC or cyst(e)ine.…”

Section: Discussionmentioning

confidence: 91%

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

Kawakami

Ohuchi

Morita

et al. 2009

J Nutr Sci Vitaminol

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…Cystine was also added to both diets ( Table 1). The effect of cysteine on homocysteine is unclear because previous studies have reported that cysteine both increases (40,41) and decreases (42) homocysteine in human subjects. The higher concentrations of homocysteine may also be attributed to insulin resistance as it occurred in the offspring with higher HOMA-IR indices at weaning (Table 5) and at week 15 (Table 3).…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Soya protein- and casein-based nutritionally complete diets fed during gestation and lactation differ in effects on characteristics of the metabolic syndrome in male offspring of Wistar rats

et al. 2011

View full text Add to dashboard Cite

The AIN-93G diets based on soya protein or casein were fed to pregnant Wistar rats from day 3 of gestation and compared for their effects on characteristics of the metabolic syndrome in male offspring. Pregnant rats were randomised to either a casein (C) or soya protein (S) diet (n 12) during gestation only (Expt 1) or during gestation and lactation (Expt 2). Male offspring were weaned to either a C or S diet for 9 weeks (Expt 1) or 15 weeks (Expt 2). In Expt 1, pups born to S-fed dams had higher fasting blood glucose (BG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 4, higher blood glucose (BG) response to a glucose administration (P,0·001) and higher body weight (BW) at week 8 (P, 0·05). In Expt 2, consumption of the S diet throughout gestation and lactation resulted in higher BW (P,0·05), DBP (P,0·005) and SBP (P,0·005) in the offspring. They also had higher homeostasis model assessment of insulin resistance (HOMA-IR; P, 0·05) and plasma homocysteine (P,0·05) at weaning, higher fasting BG and glucose response to glucose administration (P,0·005) at week 12 and higher HOMA-IR (P,0·01) at week 15. Although composition of the weaning diets interacted with the diet of the dams, the latter was the dominant factor in determining metabolic outcomes in the offspring. In conclusion, the S diet, compared with the C diet, when consumed during gestation or throughout gestation and lactation increased the presence of characteristics of the metabolic syndrome in the offspring.

show abstract

Effects of Various Amino Acids on Methionine-Induced Hyperhomocysteinemia in Rats

Cited by 6 publications

References 20 publications

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

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

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

Soya protein- and casein-based nutritionally complete diets fed during gestation and lactation differ in effects on characteristics of the metabolic syndrome in male offspring of Wistar rats

Contact Info

Product

Resources

About