Nonspecific adaptation of jejunal amino acid uptake in the rat

Luminal nutrients are a major effector of intestinal adaptation. Amino acids are trophic to the intestine, but their role in regulating amino acid transport is not well documented. The presence of several distinct amino acid transport systems raises the question of whether adaptation is class-specific. Studies were carried out in parenterally nourished rats receiving a 7-day jejunal infusion of a 3% solution of either aminoisobutyric acid, aspartic acid, glutamine, histidine, lysine, or valine. While all amino acids were trophic to the intestine, their effects on the in vitro uptake of 0.1, 1.0 and 10.0 mM aspartic acid, lysine, and valine (representative acid, basic, and neutral amino acids) were variable and nonspecific. Compared to controls receiving either total parenteral nutrition alone or total parenteral nutrition plus luminal saline, prior lysine and aspartic acid infusion significantly increased in vitro uptake of all three amino acids tested, whereas valine had little effect on transport. No effect on transport was seen with glutamine (actively metabolized by the intestine as is aspartic acid), aminoisobutyric acid (a nonmetabolizable amino acid congener), or histidine (the most trophic amino acid). In conclusion, while individual amino acids cause an adaptation of amino acid uptake, the effects are nonspecific and independent of their metabolic or trophic potential.     

Plasma and lipoprotein cholesterol in rats fed L-amino acid-supplemented diets

The effect of feeding amino acid-supplemented diets on plasma cholesterol concentration and distribution in the lipoproteins was studied on adult rats. A control diet (without any amino acid addition), and experimental diets supplemented with one of the following L-amino acids: lysine (10%), cystine (5%), methionine (1%), tryptophan (10%), valine (5%), and histidine (5%), were given for 2-4 months. Rats fed the lysine-, cystine- and tryptophan-added diets exhibited constant weights throughout the experiment, whereas those fed the other amino acid-added diets showed body weight gains quite similar to control rats. Two amino acids were shown to lower plasma cholesterol concentration: lysine (by 30%) and tryptophan (by 35%); one amino acid increased it: cystine (by 46%). The cholesterol distribution in the lipoproteins was significantly modified, principally when rats ingested cystine-enriched diets: as compared to control rats, the cholesterol concentration in lipoproteins of density between 1.040 and 1.063, and in high density lipoproteins (HDL), was increased by 174 and 58%, respectively.     

Brain uptake and release of amino acids in nondiabetic and insulin-dependent diabetic subjects: important role of glutamine release for nitrogen balance.

We measured net uptake and release of amino acids in the brain of 7 nondiabetic and six diabetic subjects. Duration of insulin-dependent diabetes (IDDM) was 19.4 +/- 2.1 years. Arteriojugular vein measurements were performed before and after 120 minutes of insulin infusion and ensuing Biostator-regulated normoglycemia. Cerebral blood flow was measured during normoglycemia by 11-CH3-F and positron emission tomography. During hyperglycemia in the IDDM subjects, arterial concentrations of valine and leucine were higher, and those of glutamic acid and arginine lower, than in nondiabetic subjects. Insulin infusion lowered levels of most amino acids in both groups. Insulin treatment did not significantly affect the uptake or release of amino acids. Significant net uptake of branched-chain amino acids was noted in both groups, as well as uptake of lysine and phenylalanine in the IDDM subjects. The sum of measured differences was not different from zero in either group. Nitrogen balance depended on impressive release of glutamine from the brain (-963 +/- 147 and -960 +/- 303 nmol/100 g/min), which amounted to 73% and 69% of net release in nondiabetic and IDDM subjects, respectively. We conclude that balance between uptake and release of amino acids is similar in nondiabetic and in long-term IDDM subjects.     

Atypical Pattern of Utilization of Amino Acids for Mitochondrial Protein Synthesis in HeLa Cells

The capacity of HeLa cell mitochondria, either isolated or in intact cells, to incorporate different labeled amino acids into proteins was investigated. Eight amino acids (alanine, arginine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, and lysine), which include most of the charged polar ones, showed a very low amount, if any at all, of chloramphenicol-sensitive incorporation, relative to that expected for an "average" HeLa-cell protein. By contrast, the most hydrophobic amino acids (leucine, isoleucine, valine, phenylalanine, and methionine) were the most actively incorporated by HeLa mitochondria. The available evidence suggests that pool effects cannot account for this general pattern of utilization of amino acids; furthermore, this pattern is in good agreement with the known hydrophobic properties of proteins synthesized in mitochondria.     

Amino acid pattern in plasma before and after jejuno-ileal shunt operation for obesity.

The amino acid pattern in plasma was studied in a reference group (n=26) and in three groups of massive obese subjects (n=9, 8, and 9 respectively) before and at intervals after jejuno-ileostomy. The obese subjects had preoperatively an amino acid pattern significantly different from that in the reference group. The concentrations of lysine, tyrosine, 1/2 cystine, and glutamic acids were higher, and aspargin, glutamine, serine, and glycine were lower than in the reference group. During the post-operative period the amino acid pattern changed significantly; thus serine, glycine, and taurine increased and valine, lysine, leucine, tryptophan, thyrosine, 1/2 cystine, and citrulline decreased. The amino acid pattern in the obese group with the longest post-operative observation time and a stable body weight differed significantly from that in the reference group only with regard to a low valine concentration and high concentration of taurine and glutamatic acid.     

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.     

Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat.

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.     

Effect of leucine on amino acid and glucose metabolism in humans.

Leucine has been reported to be an important regulator of protein metabolism. We investigated the effect of intravenous infusion of L-leucine versus saline on amino acid metabolism in eight healthy human subjects. Plasma concentrations of amino acids were measured and protein turnover was estimated using L-(1-13C)lysine and L-(3,3,3,-2H3)leucine as tracers. Glucose kinetics were measured using D-(6,6-2H2)glucose as a tracer. Leucine infusion increased the plasma leucine concentration from 103 +/- 8 to 377 +/- 35 mumol/L (P less than .01). Plasma concentrations of essential amino acids, including threonine, methionine, isoleucine, valine, tyrosine, and phenylalanine were significantly decreased by leucine infusion. Leucine infusion did not change lysine flux significantly (108 +/- 4 during saline v 101 +/- 4 mumol/kg/h-1 during leucine infusion), but decreased lysine oxidation (13.2 +/- 0.9 v 10.7 +/- 1 mumol/kg/h, P less than .05) and endogenous leucine flux (from 128 +/- 4 to 113 +/- 7 mumol/kg/h, P less than .05) when plasma (2H3) ketoisocaproate (KIC) was used for calculation. During leucine infusion, the (2H3) KIC to (2H3) leucine plasma enrichment ratio increased from 0.76 +/- 0.02 to 0.88 +/- 0.01 (P less than .001), while estimation of leucine flux using plasma (2H3) leucine showed no change in endogenous leucine flux. Leucine infusion decreased hepatic glucose production and metabolic clearance of glucose, but did not change plasma concentrations of glucose, insulin, C-peptide, glucagon, epinephrine, norepinephrine, or free fatty acids. We conclude that leucine spares glucose and lysine catabolism and decreases plasma concentrations of essential amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amino acids are not all initially attached to the same position on transfer RNA molecules.

Escherichia coli tRNA has been modified by replacement of the 3'-terminal AMP with either 3'-amino-3'-deoxy AMP of 2'-amino-2'-deoxy AMP. These tRNA analogs have enabled us to determine the initial site of enzyme-catalyzed aminoacylation of different tRNAs by the formation of aminoacyl-tRNA molecules in which the amino acid is linked to the 3'-terminal ribose through a stable amide bond. The tRNA species specific for glutamic acid, glutamine, leucine, phenylalanine, tyrosine, and valine are all aminoacylated on the 2'-hydroxyl group. The tRNA species specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, and threonine are aminoacylated on the 3'-hydroxyl group. The amino acids arginine, isoleucine, methionine, proline, serine, and tryptophan form stable amide bonds with both amino tRNA analogs. This might suggest that the synthetases for these amino acids can acylate both the 2'- and 3'-hydroxyl groups, but it is more likely that these enzymes can acylate both hydroxyl and amino groups at either the 2' or 3'-position of the tRNA. These results clearly illustrate a fundamental heterogeneity which is apparent in the mechanism of action of aminoacyl-tRNA synthetases.     

Plasma amino acid profiles, urea and ammonia —nitrogen in one- and eight-year-old ewes fed two levels of protein

The effect of age and dietary protein level on plasma amino acid, urea and ammonia concentrations were studied using one- and eigth-year-old ewes. A diet containing 10% crude protein was fed at individual maintenance levels to six ewes of each age in trial 1, followed by feeding a similar diet containing 20% crude protein in trial 1, tyrosine, valine, glutamic and aspartic acids were higher in the plasma of young ewes, while citrulline and serine were higher in the old ewes. In trial 2, isoleucine, tyrosine, methionine, alanine, leucine, valine, glutamic acid, phenylalanine, lysine and arginine were higher in young ewes, while citrulline was higher in the old animals, suggesting a differential age-related response to higher dietary protein. Total, essential, nonessential, the ratio of essential to nonessential and branched-chain amino acids did not differ by age in trial 1, while all these values except nonessential amino acids were higher in young ewes in trial 2. Plasma urea nitrogen was higher in old ewes in both trials. No age difference occured in plasma ammonia in trial 1, while old ewes had lower plasma ammonia in trial 2. The decreased plasma amino acid concentrations and elevated urea levels in old ewes at both levels of protein intake suggested increased amino acid catabolism, perhaps reflecting age differences in cellular amino acid metabolism.     

Intravenous glutamine does not stimulate mixed muscle protein synthesis in healthy young men and women

We investigated the effects of a glutamine-supplemented amino acid mixture on vastus lateralis muscle protein synthesis rate in healthy young men and women. Three men and 3 women (27.8 +/- 2.0 yr, 22.2 +/- 1.0 body mass index [BMI], 56.1 +/- 4.5 kg lean body mass [LBM]) received a 14-hour primed, constant intravenous infusion of L[1-13C]leucine to evaluate the fractional rate of mixed muscle protein synthesis. In addition to tracer administration, a clinically relevant amino acid mixture supplemented with either glutamine or glycine in amounts isonitrogenous to glutamine, was infused. Amino acid mixtures were infused on separate occasions in random order at a rate of 0.04 g/kg/h (glutamine at approximately 0.01 g/kg/h) with at least 2 weeks between treatment. For 2 days before and on the day of an infusion, dietary intake was controlled so that each subject received 1.5 g protein/kg/d. Compared with our previous report in the postabsorptive state, amino acid infusion increased the fractional rate of mixed muscle protein synthesis by 48% (P < .05); however, the addition of glutamine to the amino acid mixture did not further elevate muscle protein synthesis rate (ie, 0.071% +/- 0.008%/h for amino acids + glutamine v 0.060% +/- 0.008%/h for amino acids + glycine; P = .316). Plasma glutamine concentrations were higher (P < .05) during the glutamine-supplemented infusion, but free intramuscular glutamine levels were not increased (P = .363). Both plasma and free intramuscular glycine levels were increased when extra glycine was included in the infused amino acid mixture (both P < .0001). We conclude that intravenous infusion of amino acids increases the fractional rate of mixed muscle protein synthesis, but addition of glutamine to the amino acid mixture does not further stimulate muscle protein synthesis rate in healthy young men and women.     

Evolution and relatedness in two aminoacyl-tRNA synthetase families.

Sequence segments of about 140 amino acids in length, each containing a selected consensus region, were used in alignments of the aminoacyl-tRNA synthetases with the aim of discerning their evolutionary relationships. In all cases tested, enzymes specific for the same amino acid from a variety of organisms grouped together, reinforcing the supposition that the aminoacyl-tRNA synthetases are very ancient enzymes that evolved to include the full complement of 20 amino acids long before the divergence leading to prokaryotes and eukaryotes. The enzymes are divided into two mutually exclusive groups that appear to have evolved from independent roots. Group I, for which two sequence segments were analyzed, contains the enzymes specific for glutamic acid, glutamine, tryptophan, tyrosine, valine, leucine, isoleucine, methionine, and arginine. Group II enzymes include those activating threonine, proline, serine, lysine, aspartic acid, asparagine, histidine, alanine, glycine, and phenylalanine. Both groups contain a spectrum of amino acid types, suggesting the possibility that each could have once supported an independent system for protein synthesis. Within each group, enzymes specific for chemically similar amino acids tend to cluster together, indicating that a major theme of synthetase evolution involved the adaptation of binding sites to accommodate related amino acids with subsequent specialization to a single amino acid. In a few cases, however, synthetases activating dissimilar amino acids are grouped together.     

Experimental cystinuria: The cycloleucine model. II. Amino acid efflux from intestinal and renal tissues

Loading and unloading experiments using intestinal sacs and renal cortex slices were undertaken to ascertain the role of amino acid efflux in cycloleucine-induced amino-aciduria. The presence of cycloleucine, lysine, or valine on the luminal or antiluminal side of the intestine caused an increased leakage of [¹⁴C] cycloleucine, [¹⁴C] lysine, and [³⁵S] cystine from the tissue. Similar results were obtained when using kidney cortex slices, except for cystine efflux. The latter phenomenon was inhibited by cycloleucine and lysine. Data, also obtained with renal cortex slices, suggest that cystine and cysteine are recognized by different transport sites although one (the oxidized form) may be typically extracellular and the other (the reduced form), intracellular. A comparison of these data with previous works done in our laboratory¹⁴ shows that cycloleucine affects efflux less than influx and further suggests that in rats given cycloleucine, renal transport is impaired only at the brush border level for cystine and at both luminal and antiluminal membranes for dibasic amino acids.     

Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.     

A study of plasma free amino acid levels. V. Correlations among the amino acids and between amino acids and some other blood constituents

Possible relationships among the amino acids were examined by determining the correlation between their fasting plasma levels in 136 children and 193 adults. Leucine and isoleucine values were the most highly correlated. Threonine, serine, and glycine were significantly related in boys, girls, and men, but there was no correlation between threonine and glycine levels in women. A group of 11 amino acids appeared to be highly interrelated: These were alanine, asparagine, glutamine, valine, isoleucine, leucine, methionine, tyrosine, phenylalanine, proline, and lysine. Possible correlations between the individual amino acid levels and hemoglobin, blood glucose, plasma cholesterol, and uric acid levels were also examined. There were no highly significant relationships between amino acid levels and the levels of any of them.     

Amino acid uptake and output by the sheep hind limb.

Arteriovenous differences across the hind limb of fed sheep show release of alanine, glutamine, and tyrosine and uptake of serine, glutamate, and possibly lysine. In starved animals there is a net output of most amino acids, although the amount of alanine released, 26 nmol/ml blood, is much lower than reported for human muscle and is less than the cumulative release of valine, leucine, and isoleucine. Since it has been argued that the carbon of alanine is derived from glucose and the nitrogen from the deamination of branched chain amino acids, we suggest that either nutrient availability is limiting alanine output or else sheep muscle has an impaired ability to degrade the branched chain amino acids.     

Muscle amino acid pattern in obese rats

OBJECTIVE: To determine how the ability of skeletal muscle to manage amino acids is conditioned by obesity. The test was performed in two different models of obese rats: diet-obese rats and genetically obese rats. SUBJECTS: Lean and genetically obese (fa/fa) male Zucker rats were used. DESIGN: For up to 60 d of life lean animals were fed with standard chow pellet or with a hypercaloric cafeteria diet. Genetically obese rats were fed with standard chow pellet during the same period. MEASUREMENTS: Amino acid concentration in the femoral artery and vein and leg blood flow were measured. Free amino acid concentration, protein and nitrogen content and enzyme activities were determined in whole leg muscle. RESULTS: Amino acid availability was increased in diet-obese animals and remained unchanged in the genetically obese group. The genetically obese groups had a lower protein content and unchanged concentration of amino acids in leg muscle. Furthermore, total nitrogen remained unchanged in these animals and they showed an increased activity in alanine aminotransferase and glutamine synthetase. The leg muscle of the diet-obese rats took up several amino acids (Ala, Arg and Val) or released others (mainly Gln and Gly). Conversely, genetically obese rats took up many amino acids and did not release any. CONCLUSIONS: We conclude that in nutritionally obese rats there is an increased availability of amino acids in skeletal muscle. This augmented availability propitiates the increase in the uptake of many amino acids. In genetically obese rats, the lack of variation in amino acid availability points to a possible hereditary alteration that increases the capacity of different amino acid transport systems. Furthermore, the diminished protein content of fa/fa muscle is not due to a lower availability and intracellular pool of amino acids.     

感染食蟹猴疟原虫的大劣按蚊血淋巴和胃水解物氨基酸分析

大劣按蚊感染食蟹猴疟原虫B株后第10d,血淋巴内的蛋氨酸、异亮氨酸、亮氨酸、鸟氨酸、赖氨酸含量均较对照组低。第9d蚊胃水解物分析结果表明,感染蚊胃中的多数氨基酸含量增加,其中缬氨酸、蛋氨酸、酪氨酸的含量是对照组3倍以上,氨基酸的总量比对照组高70％以上。     

Analysis of amino acids in hemolymph and acid hydrolysates of midguts of Anopheles dirus infected with Plasmodium cynomolgi

Quantitative determinations of free amino acids in hemolymph and acid hydrolysates of midguts of female Anopheles dirus infected with Plasmodium cynomolgi bastianellii were carried out and the results were compared with those of noninfected mosquitoes. On day 10 after infected blood meal, the contents of methionine, isoleucine, leucine, ornithine, lysine in the hemolymph of infected mosquitoes markedly decreased as compared with those in the controls. However, the quantitative analysis of the amino acids of the acid hydrolysates of the midguts from infected mosquitoes on day 9 after an infected blood meal showed that the content of their total amino acids was 70% more than that in the controls, with special reference to aspartic acid, glutamic acid, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan.     

Whole body leucine and lysine metabolism studied with [1-13C]leucine and [α-15N]lysine: Response in healthy young men given excess energy intake

An excess intake of dietary energy in adult subjects enhances body N balance but the mechanism(s) responsible remains unknown. Thus, dynamic aspects of metabolism of whole body leucine and lysine were explored in healthy young adult men, receiving adequate or excess energy intakes, using a primed, continuous intravenous infusion of a mixture of L-[¹³C]leucine and L-[α-¹⁵N]lysine to provide a constant enrichment of plasma free leucine and lysine over a period of 2 hr. Twelve subjects were studied with the labeled amino acids following an overnight fast (post-absorptive state) and 12 additional subjects while consuming small isocaloric, isonitrogenous horly meals (fed state). Preceding each infusion, subjects were adapted for 7 days to experimental diets, providing a constant and barely adequate protein intake of 0.6 g/kg body weight/day, at either a maintenance energy intake, determining from estimates of usual food intake that maintain body weight, or an energy intake 25% greater than the maintenance level. The excess non-protein energy intake was given as an isocaloric mixture of carbohydrate and fat (eight subjects) or entirely as either carbohydrate or fat (eight subjects each). Whole body leucine and lysine flux remained unchanged with excess energy intakes, regardless of the source of energy substrate. Based on the combined data with all energy intake sources, the rate of leucine oxidation was significantly reduced and the rate of leucine incorporation into body protein showed a small increase with excess energy intakes. Thus, when expressed as net protein gain (leucine incorporation into body protein minus leucine release from protein breakdown) a significantly greater rate of body protein retention occurred with excess energy intake and this was more marked for the high carbohydrate diets. Mean change in body leucine retention determined by ¹³C-leucine was in good agreement with that calculated from alterations in overall N balance. In addition, the rate of inflow of leucine and of lysine into the metabolic pool via tissue protein breakdown was reduced with ingestion of meals. These results indicate that excess energy intake improves overall body N balance by reducing amino acid oxidation and enhancing protein synthesis. Furthermore, these effects are particularly evident at a time when passage of amino acids to tissues is stimulated by ingestion and absorption of meals.