Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes

We showed previously that 64% of the total dietary sulfur amino acid (SAA) requirement could be supported by dietary cysteine (Cys). However, the observation of such a sparing effect may be affected by the dietary intakes of SAA provided. The aim of this study was to compare methionine (Met) metabolism and transsulfuration (TS) in five healthy men fed three different diets (in random order) for 3 d each, with varying combinations of Met and Cys: 24 mg Met/(kg. d) and no Cys (diet A); 13 mg Met/(kg. d) and 11 mg Cys/(kg. d) (diet B); and 5 mg Met/(kg. d) and 19 mg Cys/(kg. d) (diet C). On d 3, Met kinetics and TS were assessed using orally administered L-[1-(13)C, methyl-(2)H(3)]methionine. Met demethylation (transmethylation, TM) significantly decreased as the dietary Met to Cys ratio decreased. Met TS was significantly lower during diets B [2.8 +/- 0.4 micro mol/(kg. h)] and C [1.5 +/- 0.5 micro mol/(kg. h)] than during diet A [7.8 +/- 2.9 micro mol/(kg. h)] (P < 0.05). The results of the present study indicate that when the ratio of Met to Cys fed is typical of that found in major food proteins and total SAA are sufficient to meet requirements, TS is significantly reduced compared with the case in which SAA needs are supplied by Met alone. We conclude that Cys sparing occurs through an increase in the fraction of the homocysteine pool destined for RM relative to TS (RM:TS).     

Hepatic sulfur amino acid metabolism in rats with chronic renal failure

We recently demonstrated elevated plasma amino acid concentrations and abnormal responses to amino acid supplementation (e.g., elevated methionine and phenylalanine) in children with chronic renal failure (CRF). We also recently developed an improved model of CRF in which animals manifest abnormal tissue amino acid levels, marked anorexia and growth failure. The objective of the current study was to determine the etiology of elevations of sulfur amino acids in animals with chronic renal failure. Chronic renal failure, defined as creatinine clearance less than 30% of control values, was induced in male rats in a two-stage surgical procedure. Four groups were studied over 2, 4 and 6 wk: control (non-operated) control (sham-operated), pair-fed (sham-operated and pair-fed with uremics) and CRF. Animals with CRF were anorexic and growth-retarded. Although plasma sulfur amino acid levels tended to be lower in the uremic animals than in controls, hepatic tissue concentrations were higher. Methionine adenosyltransferase was higher, but cystathione synthase and cystathionase activities were not significantly different in rats with CRF compared to pair-fed controls. We conclude that uremia, not malnutrition, affected sulfur amino acid metabolism and that with CRF, a normal adaptive response to elevated methionine levels was occurring, sufficient to normalize sulfur amino acid pool size. Alternative causes of elevated sulfur amino acids must be sought.     

Respective contribution of plasma branched-chain amino acids and 2-keto acids to the hepatic metabolism of the carbon moiety of branched-chain amino acids in fed rats

The splanchnic balances of branched-chain amino acids (BCAA) and ketoacids (BCKA) concentrations were compared in rats fed a 15% (basal) or a 70% (HP) casein diet. Arterial BCAA concentrations were four- to fivefold and BCKA concentrations were twofold higher in rats fed HP diet than in rats fed basal diet. In rats fed basal diet, a higher proportion (45-58%) of BCKA was removed by the liver than of BCAA (7-12%). Thus, plasma BCKA were probably the major source of substrates for hepatic BCKA dehydrogenase. In rats fed HP diet, hepatic uptake of BCAA was 10 times greater than in rats fed basal diet, owing to their higher extraction; BCKA uptake was only twice as great; thus BCKA were a minor source of substrates for hepatic metabolism. In both diet groups, uptake of ketomethylvalerate (KMV) was less efficient than ketoisovalerate (KIV) or ketoisocaproate (KIC) uptake. Studies of metabolism of intraportal loads of BCKA showed that capacities for KIV and KIC uptake were high, KMV uptake plateaued at lower portal concentrations. With HP diets, the liver may be the major site of BCAA utilization; the interorgan transfer of the carbon moiety of BCAA to the liver as ketoacids does not keep pace with an increased availability of BCAA.     

Nutritional and functional importance of intestinal sulfur amino acid metabolism

The metabolism of sulfur amino acids, methionine and cysteine, has been linked to several key aspects of human health and cellular function. In addition, the metabolism of dietary amino acids by the gastrointestinal tract is nutritionally important for normal function. In the case of sulfur amino acids (SAAs), in vivo, stable isotope studies in adults suggest that the splanchnic tissues utilize as much as 30-44% of the dietary methionine and cysteine. Similarly, the dietary methionine requirement is 30% lower in total parenteral nutrition (TPN)-fed piglets, a condition in which dietary nutrients largely bypass intestinal metabolism. These data suggest that intestinal metabolism of methionine is substantial, yet the intestinal metabolic fate of dietary methionine is largely unknown. Dietary cysteine likely plays a key role in intestinal epithelial antioxidant function as a precursor for glutathione. Moreover, cysteine and glutathione may also regulate epithelial cell proliferation via modulation of redox status. Recent evidence indicates that transformed colonic epithelial cells are capable of methionine transmethylation and transsulfuration. This review discusses the evidence of intestinal SAA metabolism and how this affects nutrient requirements and epithelial function.     

Splanchnic metabolism of ingested amino acids in neonates

PURPOSE OF REVIEW: Neonates typically show rapid growth. Nutrient absorption in the neonatal period is higher than during any other time in life so as to meet the requirements for this rapid growth. Generally, nutrients are administered enterally, and in the past the gut was considered to absorb and digest these nutrients without major metabolism. Recent animal and human work has, however, revealed that the intestine and other splanchnic tissues contribute significantly to whole-body metabolism, and have their own specific functions. This review focuses on these observations. RECENT FINDINGS: The splanchnic tissues take up greatly different proportions of each of the amino acids, ranging from 80-100% for threonine and several nonessential amino acids to 15-30% for lysine. The metabolic fates of the utilized substrates differ as well. Some are predominantly used for constitutive protein synthesis, others for energy generation or for formation of (glyco-)proteins that are secreted into the lumen. Glucose appears to be the major contributor to energy generation, but amino acids are important as well. SUMMARY: Both animal and human studies have shown that the intestine uses substantial amounts of dietary amino acids. This has several implications for the nutritional needs of infants to maintain growth, especially during times of inadequate enteral nutrition.     

Insulin and amino acids both strongly participate to the regulation of protein metabolism

PURPOSE OF REVIEW: The application of tracer kinetic methods, combined with measurements of the activity of components of the cellular signaling pathways involved in protein synthesis and degradation, affords new insights into the regulation of skeletal muscle protein metabolism in vivo in humans. Feeding is associated with an increase in protein synthesis and a decrease in proteolysis. These changes are mediated by feeding-induced increases in plasma concentrations of both nutrients and hormones. RECENT FINDINGS: Recent studies definitely demonstrated that insulin and amino acids directly interacted in promoting postprandial anabolism. However, the contribution of amino acids was abolished in old individuals in whom only insulin action persisted. There was a line of evidence that the effect of amino acids originates from leucine, which should not be viewed simply as a building block for protein synthesis, but as a signal in the regulation of cell functions. Although their cellular signaling pathways do not completely overlap, insulin and amino acids both activate the translation initiation of protein synthesis. Insulin presumably inhibits skeletal muscle protein degradation through a decrease in the activity of the ubiquitin proteasome-dependent pathway. SUMMARY: Whether or not amino acids modify insulin action and have specific effects on proteolysis has not yet been documented. At the molecular level, amino acids such as insulin modulate gene expression. Such studies are needed to gain a better understanding of the interactions between insulin and amino acids in the regulation of skeletal muscle protein anabolism.     

慢性肾衰时蛋白质和氨基酸代谢的研究

慢性肾功能不全患普遍存在蛋白质／氨基酸代谢异常。其可能机制和影响因素主要包括厌食、低蛋白饮食及对低蛋白饮食适应性的损伤、酸中毒、激素抵抗、能量代谢的异常、细胞因子的异常及支链氨基酸代谢异常等。目前营养和药物治疗包括低蛋白饮食并补充铜酸／氨基酸制剂，使用影响蛋白质／氨基酸代谢的药物生长激素、重组人促红细胞生成素和磷酸二酯酶抑制剂Pentoxifylline和Amrinone等。     

条件必需氨基酸营养代谢与肠道健康

正常肠屏障功能的维持主要依赖于肠黏膜屏障.每天食人的氨基酸是肠黏膜的主要物质,也是合成肠道蛋白、一氧化氮和各种代谢产物的重要底物,具有维持肠道的完整性和生理功能.现就Gln、谷氨酸和精氨酸在肠道健康的营养和免疫的作用作一综述.     

Effects of decreased availability of sulfur amino acids in severe childhood undernutrition

In studies of glutathione (GSH) metabolism in children with severe childhood undernutrition (SCU), slower erythrocyte GSH synthesis in children with edema was associated with lower concentrations of cysteine, the rate-limiting precursor of GSH synthesis. This finding suggested a shortage of cysteine available for GSH synthesis in children with edematous SCU. The plasma concentration of methionine, the sulfur donor for cysteine synthesis, was also lower in children with edematous SCU, suggesting decreased availability of methionine for cysteine synthesis. It is also possible that reduced methionine availability will result in decreased synthesis of S-adenosylmethionine, which could lead to an overall defect in methylation reactions. This review focuses on the relationship between cysteine availability and GSH synthesis in children with SCU. It also examines whether there is an inadequate supply of cysteine in those with edematous SCU and, if so, whether this is due to a shortage of methionine due to a decreased release of methionine from protein breakdown. Finally, the review explores whether a shortage of methionine results in decreased synthesis of S-adenosylmethionine, the universal methyl donor.     

Phagocytosis and resistance to Salmonella typhimurium infection in mice fed with lipidic diet

The peritoneal macrophages from mice on a lipidic diet have shown an increase of surface hydrophobicity of cytoplasmatic membrane. This fact is correlated with a decrease of the phagocytic index and with an impairment of Salmonella typhimurium.[/p]Corresponding author.     

Renal metabolism of amino acids: its role in interorgan amino acid exchange

The kidneys play a role in the synthesis and interorgan exchange of several amino acids. The quantitative importance of renal amino acid metabolism in the body is not, however, clear. We review here the role of the kidney in the interorgan exchange of amino acids, with emphasis on quantitative aspects. We reviewed relevant literature by using a computerized literature search (PubMed) and checking relevant references from the identified articles. Our own data are discussed in the context of the literature. The kidney takes up glutamine and metabolizes it to ammonia. This process is sensitive to pH and serves to maintain acid-base homeostasis and to excrete nitrogen. In this way, the metabolism of renal glutamine and ammonia is complementary to hepatic urea synthesis. Citrulline, derived from intestinal glutamine breakdown, is converted to arginine by the kidney. Renal phenylalanine uptake is followed by stoichiometric tyrosine release, and glycine uptake is accompanied by serine release. Certain administered oligopeptides (eg, glutamine dipeptides) are converted by the kidneys to their constituent components before they can be used in metabolic processes. The kidneys play an important role in the interorgan exchange of amino acids. Quantitatively, for several important amino acids, the kidneys are as important as the gut in intermediary metabolism. The kidneys may be crucial "mediators" of the beneficial effects of specialized, disease-specific feeding solutions such as those enriched in glutamine dipeptides.     

Erythrocytic enzymes and amino acids related to glutamic acid metabolism in childhood hypoproteinemic states

The erythrocyte enzymes of glutamic acid metabolism (glutaminase I, glutaminase II, glutamic acid decarboxylase, glutamine synthetase, and transaminases) and related amino acids (glutamine, glutamic acid, aspartic acid, alanine, and gamma-aminobutyric acid) were estimated in 69 children with protein-energy malnutrition, 13 with nephrosis, and 10 with Indian childhood cirrhosis. Twenty-one apparently healthy children served as controls. There was a significant increase in the activities of erythrocytic glutaminase I, glutaminase II, glutamic acid decarboxylase, and glutamine synthetase in all the three hypoproteinemic states, while the activities of the transaminases showed a decrease in all the conditions. The concentrations of all the amino acids were significantly increased in both the varieties of protein-energy malnutrition (edematous and nonedematous). In nephrosis and Indian childhood cirrhosis, aspartic acid, alanine, and gamma-aminobutyric acid showed a significant rise. The concentration of glutamic acid was also significantly increased in nephrosis. The observations of the present study suggest an increase in intracellular production of glutamic acid in hypoproteinemia.     

Total sulfur amino acid requirement and metabolism in parenterally fed postsurgical human neonates

BACKGROUND: Except for tyrosine, the amino acid requirements of human neonates receiving parenteral nutrition (PN) have not been experimentally derived. OBJECTIVES: The objectives were to determine the total sulfur amino acid (TSAA) requirement (methionine in the absence of cysteine) of postsurgical, PN-fed human neonates by using the indicator amino acid oxidation (IAAO) technique with L-[1-(13)C]phenylalanine as the indicator. DESIGN: Fifteen postsurgical neonates were randomly assigned to receive 1 of 18 methionine intakes ranging from 10 to 120 mg x kg(-1) x d(-1), delivered in a customized, cysteine-free amino acid solution. Breath and urine samples were collected for the measurement of (13)CO(2) and amino acid enrichment. Blood samples were collected at baseline and after the test methionine infusion for the measurement of plasma methionine, homocysteine, cystathionine, and cysteine concentrations. RESULTS: Breakpoint analysis determined the mean TSAA requirements to be 47.4 (95% CI: 38.7, 56.1) and 49.0 (95% CI: 39.9, 58.0) mg x kg(-1) x d(-1) with the use of oxidation and F(13)CO(2), respectively. CONCLUSIONS: This is the first study to report the TSAA requirement of postsurgical, PN-fed human neonates. The estimated methionine requirement expressed as a proportion of the methionine content of current commercial pediatric PN solutions was 90% (range: 48-90%) of that found in the lowest methionine-containing PN solution.