High levels of dietary amino and branched-chain alpha-keto acids alter plasma and brain amino acid concentrations in rats

Plasma and brain amino acid and plasma branched-chain alpha-keto acid (BCKA) concentrations were measured in rats fed diets containing high levels of individual amino and alpha-keto acids. Consumption of a low-protein (9% casein) diet high in leucine or alpha-ketoisocaproate depressed plasma concentrations of isoleucine and valine and their respective keto acids, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. High dietary levels of alpha-keto-beta-methylvalerate or alpha-ketoisovalerate (but not of isoleucine or valine) depressed plasma concentrations of the other BCKA and their respective branched-chain amino acids (BCAA). Consumption of a low protein, high phenylalanine diet depressed plasma concentrations of both BCAA and BCKA. Brain large neutral amino acid pools of rats fed all low-protein, high-amino acid diets were depleted. Consumption of diets high in individual BCKA increased brain concentrations of aromatic amino acids. In this study of rats allowed to feed for only 6 h/d, elevated brain phenylalanine concentration was associated with a significant depression of food intake, whereas elevated brain BCAA concentrations were not. Also, elevated plasma BCKA concentrations, comparable with those observed in maple syrup urine disease, were accompanied by elevations in concentrations of aromatic amino acids in brain but not in plasma.     

Adaptation of rats to diets containing different levels of protein: effects on food intake, plasma and brain amino acid concentrations and brain neurotransmitter metabolism

Food intake, plasma and brain amino acid concentrations, liver amino acid catabolic enzyme activities, and whole-brain neurotransmitter and metabolite concentrations were measured in young rats adapted for 11 d to diets containing from 5 to 75% (in increments of 5%) casein. Food intake was depressed initially in rats fed diets containing 5, 10% or greater than 35% casein. For the duration of the experiment, food intakes of the groups fed the higher protein diets improved on successive days; the length and severity of the depression were proportional to the protein content of the diet fed. Rats fed low levels of protein grew poorly, and their food intake remained depressed. The gradual improvement in growth and food intake of rats fed diets containing more than 35% casein was accompanied by dramatic increases in the activities of serine-threonine dehydratase (SDH, EC 4.2.1.16) and glutamate-pyruvate aminotransferase (GPT, EC 2.6.1.1) in liver. The increase in amino acid catabolic activity was accompanied by decreases in the concentrations of most amino acids in plasma and brain. However, concentrations of branched-chain amino acids, in both plasma and brain, increased in direct proportion to the protein concentration of the diet fed. As a result of these reciprocal responses, the total concentration of indispensable amino acids in brain (IAA) was maintained within a narrow range of values, despite a sixfold range of protein intakes. Whole-brain concentrations of norepinephrine, dopamine and serotonin were not correlated with dietary protein concentration, total food intake or protein intake. Brain concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were correlated inversely with protein intake and that of 3,4-dihydroxyphenylacetic acid was correlated directly with food intake. Protein intake appeared to be related to the animal's ability to maintain brain total IAA content between some upper and lower limits. Our results indicate that this was accomplished initially through downward adjustment of protein intake and subsequently through an increase in catabolic capacity for the amino acids.     

Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal amino acid pools in experimental maternal phenylketonuria

BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p-chlorophenylalanine, and L-phenylalanine in the diet. OBJECTIVE: We studied whether a dietary mixture of several large neutral amino acids (LNAAs) would improve fetal brain growth and normalize the fetal brain amino acid profile in a rat model of maternal PKU induced by DL-alpha-methylphenylalanine (AMPhe). DESIGN: Long-Evans rats were fed a basal diet or a similar diet containing 0.5% AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of gestation in experiments to test various mixtures of LNAAs. Maternal weight gains and food intakes to day 20, fetal body and brain weights at day 20, and fetal brain and fetal and maternal plasma amino acid concentrations at day 20 were measured. RESULTS: Concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were higher and fetal brain weights were lower in rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, fetal brain growth was higher and concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were lower in rats fed the AMPhe + Phe diet plus LNAAs than in rats fed the diet containing AMPhe + Phe alone. CONCLUSION: LNAA supplementation of the diet improved fetal amino acid profiles and alleviated most, but not all, of the depression in fetal brain growth observed in this model of maternal PKU.     

Induction of lysine imbalance in rats: relation to competition for lysine transport into the brain in vitro

The ability of amino acids inhibitory of lysine transport into brain slices to induce lysine imbalance was determined by feeding wheat gluten or casein diets with additions of such amino acids. Lysine transport was only moderately inhibited by amino acids; the most effective were basic amino acids or mixtures of indispensable (IAA) or branched chain amino acid (BCAA). Only mild depressions in growth and food intake occurred during a 10-day period when male, 60--65 g rats of the Sprague-Dawley strain were fed lysine-limiting, 18% wheat gluten diets with additions of these amino acids. The effects were prevented by added lysine. Rats allowed a choice between the lysine-imbalanced or non-protein diets selected the imbalanced, wheat gluten diets (in severe imbalances rats will choose the non-protein diet). Growth depression, prevented by added lysine, occurred in rats fed a 6% casein diet supplemented with IAA; individual amino acids were ineffective. Growth depressions also occurred when rats were fed a basal diet containing 6% case in + 5% of an equimolar mixture of nine IAA and supplemented with arginine or more IAA; BCAA were less effective. Additional lysine completely prevented the growth depressions, but growth of rats fed the diets containing arginine and BCAA was greater than that of those fed the extra IAA. It is difficult to induce a severe lysine imbalance; this is consistent with the failure of amino acids to cause under our conditions strong inhibition of lysine transport into brain.     

Branched-chain and other amino acids in tissues of rats fed leucine-limiting amino acid diets containing norleucine

Amino acid concentrations were measured in plasma, brain, muscle and liver from rats fed leucine-limiting diets containing varying proportions of other indispensable amino acids (IAA), the branched-chain amino acids (BCAA) and norleucine, a BCAA analog known to compete with large neutral amino acids (LNAA) for transport into tissues. Leucine was low and other IAA were high when dietary IAA were 125% and leucine was 65% of requirements; higher leucine and lower IAA concentrations occurred when dietary IAA were 75% of requirements. Tissue leucine was high and isoleucine and valine were low in rats fed excess leucine. Norleucine induced dose-dependent reductions in BCAA, especially in brain and muscle in which isoleucine or valine were sometimes undetectable. Leucine was not depressed further when control values were low as in the rats fed 125% IAA. Norleucine frequently prevented the high BCAA found after feeding additional BCAA. Other LNAA tended to be low in the brain and muscle of rats fed norleucine. Lysine was high only in the tissues of rats fed 75% IAA and norleucine; this effect was prevented when added leucine was given. Brain tryptophan, but not always serotonin, was low in rats fed norleucine. The results show transport-related, selective and usually marked depletions of tissue BCAA in rats fed norleucine; this suggests norleucine may be an aid in the treatment of clinical conditions involving excesses of BCAA.     

Brain histidine and food intake in rats fed diets deficient in single amino acids

Histidine (His) is elevated in plasma and brain during protein deficiency as well as in several pathological conditions, leading to the possibility of a direct effect on central nervous system (CNS) function. In this study, groups of weanling rats were fed diets containing graded levels of casein or a single indispensable amino acid (IAA: Leu, Val, Ile, Phe, Trp, Thr, Met or Lys) in order to produce nutritionally-deficient states. Body weight gains and food intakes were recorded daily for 2 wk. Whole brain and serum samples were obtained and analyzed for amino acid (AA) content. All weight gain and food intake responses could be predicted by the Saturation Kinetics Model. The only consistent pattern observed in AA profiles which could be correlated with food intake was an increase in brain His concentrations. Limiting dietary casein or IAA elevated brain His above controls 2.5- and 1.5-fold, respectively. Food intake was generally depressed by 50% at brain His concentrations above 105 nmol/g. Since His is the precursor of the depressant neurotransmitter histamine (HA), systemic increases may be significant in that HA could be a possible cause of the anorexia observed in protein and IAA deficiency.     

Histidine-imbalanced diets stimulate hepatic histidase gene expression in rats.

A high protein concentration in the diet induces the gene expression of several amino acid degrading enzymes such as histidase (Hal) in rats. It is important to understand whether the amino acid pattern of the dietary protein affects the gene expression of these enzymes. The purpose of the present work was to study the effect of a histidine-imbalanced diet on the activity and mRNA concentration of rat hepatic histidase. Seven groups of six rats were fed one of the following diets: 1) 6% casein (basal), 2) 20% casein, 3) 35% casein, 4) an imbalance diet containing 6% casein plus a mixture of indispensable amino acids (IAA) equivalent to a 20% casein diet without histidine (I-20), 5) 6% casein plus a mixture of IAA equivalent to a 35% casein diet without histidine (I-35), 6) a corrected diet containing 6% casein plus IAA including histidine equivalent to a 20% casein diet, 7) a corrected diet containing 6% casein plus IAA including histidine equivalent to a 35% casein diet. Serum histidine concentration was inversely proportional to the protein content of the diet, and it was significantly higher in rats fed the corrected diets compared to their respective imbalanced diet groups. Hal activity increased as the protein content of the diet increased. Greater histidine imbalance resulted in lower food intake and higher Hal activity. Rats fed histidine-corrected diets had lower activity than their respective imbalanced groups. Differences in Hal activity were associated with differences in the concentration of Hal mRNA. These results indicate that rats fed a histidine-imbalanced diet exhibit reduced food intake and weight gain and increased Hal gene expression as a consequence of an increased amino acid catabolism.     

Effects of amino acid imbalance and protein content of diets on food intake and preference of young, adult, and diabetic rats.

Effects of histidine or methionine imbalance and dietary levels (3-50%) of casein on food intake and preference of young, adult, and diabetic (2.5 month old) rats were examined. Depressions in food intake and growth caused by ingestion of the imbalanced diet were greatest in young rats and least or absent in diabetic rats. Alloxan diabetes induced hyperphagia and elevated concentrations of plasma branched-chain amino acids and decreased concentrations of tryptophan and tyrosine. The diabetic rats fed the imbalanced diet for 9 days had a higher concentration of the limiting amino acid in the plasma than the adult normal rats fed the same diet. The diabetic rats preferred the imbalanced diet over a protein-free diet when they were fed these diets concurrently. Ingestion of the imbalanced diet by normal rats caused greater changes in plasma and brain amino acid patterns than did the protein-free diet. Unlike the diabetic rats, the normal rats, especially the young rats, strongly preferred the protein-free diet over the imbalanced diet. The normal rats also preferred a 10% casein diet supplemented with L-methionine over a low or high casein diet. It seemed that young rats were able to select a protein diet that supported maximal growth when proportions of dietary amino acids were balanced. It also seemed that the susceptibility of the rats to amino acid imbalance varied directly with the status of overall protein synthesis of the animals.     

Substitution of high-dose sucrose with fructose in high-fat diets resulted in higher plasma concentrations of aspartic acid,cystine, glutamic acid,ornithine and phenylalanine,and higher urine concentrations of arginine and citrulline

High fructose intake has been shown to increase circulating alanine transaminase in humans, which could reflect damage to the liver by fructose but could also be linked to higher level of transamination of amino acids in liver. Therefore, we hypothesized that a diet with high content of fructose would affect the amino acid composition in rat plasma and urine differently from a diet with high sucrose content. Because high intake of sucrose and fructose is often accompanied with high intake of saturated fat in the Western-style diet, we wanted to compare the effects of high fructose/sucrose in diets with normal or high content of coconut oil on individual free amino acids plasma and urine. Male Wistar rats were fed diets with normal (10 wt%) or high (40 wt%) content of sucrose or fructose, with normal or high fat content (7 or 22 wt%) and 20 wt% protein (casein). Rats fed high-fructose high-fat diet had higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine, and phenylalanine and higher urine concentrations of arginine and citrulline when compared to rats fed high-sucrose high-fat diet. Substituting normal content of sucrose with fructose in the diets had little impact on amino acids in plasma and urine. Serum concentrations of alanine transaminase, aspartate transaminase, and creatinine, and urine cystatin C and T cell immunoglobulin mucin-1 concentrations were comparable between the groups and within normal ranges. To conclude, substituting high-dose sucrose with high-dose fructose in high-fat diets affected amino acid compositions in plasma and urine.     

The quality and quantity of dietary protein affect brain protein synthesis in rats.

The influence of the amino acid supply in diets with different quality and quantity of protein on the rate of protein synthesis in the brain was investigated. Amino acid concentrations in serum and brain altered in accordance with the amino acid levels of the diets, with the exception of some amino acids such as aspartic acid, glutamic acid, glycine and threonine. When rats were fed various levels of dietary casein (0, 5 and 20%), the aggregation of ribosomes increased and the fractional rate of protein synthesis tended to increase with the increase in dietary protein. When rats were fed a 20% casein diet, greater aggregation of brain ribosomes and protein synthesis rate were observed compared with those in rats fed 20% wheat gluten or gelatin diets. The RNA activity was related to the degree of the aggregation of brain ribosomes and the fractional rate of protein synthesis.     

Effects of dietary excesses of the branched-chain amino acids on growth, food intake and plasma amino acid concentrations of kittens

The effect of excesses of the branched-chain amino acids (BCAA), particularly leucine, on growth, food intake and plasma amino acid concentrations were investigated in kittens. Effects of excess leucine were tested in kittens fed five basal diets that varied in their nitrogen and amino acid contents. Compared to rats, kittens were much less sensitive to excesses of the BCAA. Addition of 10% leucine to basal diets that provided nitrogen just at or below the minimal requirement of kittens resulted in no change or increased growth and food intake of kittens when the isoleucine and valine concentrations in the basal diet were just at or slightly in excess of the kitten's minimal requirements for those amino acids. An adverse effect of leucine added to low nitrogen basal diets was observed only when isoleucine and valine were provided below the kitten's requirement (80% of requirement). When basal diets containing adequate nitrogen (24% amino acids) were tested, the addition of leucine (10%) resulted in an adverse effect when isoleucine and valine were provided at 80% of the kitten's requirement and in mild growth depressions when isoleucine and valine were provided at 1.1 times the requirement. Leucine-induced growth depression was alleviated by the addition of isoleucine and valine at 0.5%, indicating that excess leucine caused a BCAA antagonism or an amino acid imbalance. With the addition of leucine to the basal diets, there were consistent decreases in concentrations of alanine and tyrosine in plasma but no consistent depressions in the concentrations of isoleucine and valine.     

Effect of wheat and Bengalgram diets on brain glutamate metabolism in postweanling rats

Six groups of five female rats each aged 6 weeks at start were fed different diets for a period of 15 days. The protein sources of diets used were: a) 10% casein: b) wheat: c) Bengalgram: d) wheat + lysine: and e) Bengalgram + methionine + cystine + tryptophan, all containing 1.6 g nitrogen/100 g, and f) 20% casein (3.2 g nitrogen/100 g diet). The group of five rats fed a 10% casein diet served as control. It was observed that total brain RNA, protein and free alpha amino nitrogen content and protein/DNA ratio were significantly decreased on wheat and Bengalgram diets as compared to the control. The specific activities of glutamine synthetase, glutaminase I, glutaminase II and glutamate decarboxylase and concentrations of aspartic acid, glutamic acid, glutamine and gamma-aminobutyric acid (GABA) in the brain were also decreased on wheat and Bengalgram diets. The fortification of wheat with lysine and of Bengalgram with methionine, cystine and tryptophan did not alter brain weight and DNA content. While brain RNA, protein free alpha amino nitrogen (F alpha AN) and activities of enzymes of glutamic acid metabolism and related amino acid levels were restored, the activity of enzyme glutamine transferase and alanine concentration remained unaltered on various diets fed. The observations on 20% casein diet showed that levels were similar to those observed on 10% casein diet.     

The nutritive value and safety of D-phenylalanine and D-tyrosine in mice

Growth studies in mice fed synthetic amino acid diets showed that: 1) the biological utilization of D-phenylalanine relative to its L-isomer ranged from 28-81%, depending on the respective concentrations of these amino acids in the diet; 2) L-tyrosine can replace about one-half of the L-phenylalanine needed to achieve maximum weight gain and 3) D-tyrosine has no similar sparing effect on L-phenylalanine. In fact, addition of D-tyrosine to amino acid or casein diets depressed weight gain to 10% that of the control. This inhibition was significantly reduced by increasing the L-phenylalanine content of the amino acid diets and the protein content of the casein diets. Growth inhibition, therefore, appears to be related to the ratio of D-tyrosine to L-phenylalanine and possibly other amino acids in the diet, rather than to the absolute levels of D-tyrosine. Mechanistic rationalizations are offered to account for the toxic or antinutritional manifestation of D-tyrosine.     

Plasma ammonia, plasma, brain and liver amino acids and urea cycle enzyme activities in rats fed ammonium acetate

Male Sprague-Dawley rats were trained to eat a 6% casein diet within a 3-h period each day. They were then fed a 6% casein diet for 10-16 d before they were fed either the same 6% casein diet or the 6% casein diet supplemented with 15% ammonium acetate for 1 or 7 d. During the absorptive period, plasma ammonia, plasma amino acids and brain amino acids were measured on d 1 and d 7 after feeding ammonium acetate. Food intake of rats fed 15% ammonium acetate was depressed on d 1 and increased to approximately 75% of the intake of the 6% casein-fed group by d 7. On d 1 plasma ammonia of the rats fed 5% ammonium acetate was 101 microM as compared to 56 microM for the rats fed 6% casein (P less than 0.05). On d 7, plasma ammonia of the rats fed 15% ammonium acetate was 240 microM (P less than 0.05) as compared to 44 microM for the rats fed 6% casein. In rats fed 15% ammonium acetate, after 7 d ornithine transcarbamylase and arginase activities were higher and argininosuccinate synthetase activity was lower (P less than 0.05) while carbamyl phosphate synthetase activity tended to be higher than that of rats fed 6% casein. The results suggest that rats adapt to ingestion of 15% ammonium acetate by some unknown neural mechanism rather than by increases in all urea cycle enzyme activities. Feeding ammonium acetate causes changes in plasma, brain and liver amino acid concentrations.     

Dietary glutamine enhances cytokine production by murine macrophages

To examine the effects of dietary glutamine on cytokine production by macrophages, mice were fed for 2 wk on a control diet that included 200.0 g casein/kg providing 19.6 g glutamine/kg or a glutamine-enriched diet that provided 54.8 g glutamine/kg partly at the expense of casein. There were no differences in weight gain between animals fed the two diets. The plasma concentrations of a number of amino acids differed according to the diet fed; this variation largely reflected the variation in the levels of the different amino acids in the diets. Plasma glutamine concentration was not significantly affected by dietary glutamine level. The production of three cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, was greater for lipopolysaccharide-stimulated macrophages from mice fed the glutamine-enriched diet. Thus, increasing the amount of glutamine in the murine diet enhances the ability of macrophages to respond to stimulation, at least in terms of cytokine production. These observations suggest that increasing the availability of glutamine orally could promote immune responses involving macrophage-derived cytokines.     

Effects on plasma amino acid concentrations and hepatic branched-chain alpha-keto acid dehydrogenase activity of feeding rats diets containing 9 or 50% casein

Plasma concentrations of amino acids and alpha-ketoisocaproate and alpha-keto-gamma- methiolbutyrate decarboxylation activities in livers of rats trained to eat 9 or 50% casein diets for 5 hours/day, were measured one-half hour before and one-half and 3 hours after the start of the feeding period. Decarboxylation of both alpha-ketoisocaproate and alpha-keto-gamma- methiolbutyrate by liver increased significantly within one-half hour after rats had ingested either the 9 or the 50% casein diet. Liver decarboxylation activity of rats fed the 50% casein diet was from two- to fivefold higher than that of rats fed the 9% casein diet. The greatest difference was observed when calcium, NAD and coenzyme A were included in the decarboxylation assay medium. Although the activity of the branched-chain alpha-keto acid dehydrogenase increased in response to food ingestion, plasma concentrations of branched-chain amino acids also increased greatly after the ingestion of food. The similarity in the responses of alpha-ketoisocaproate and alpha-keto-gamma- methiolbutyrate decarboxylation in rats fed diets differing in protein content and subjected to different feeding regimens allows us to suggest that the branched-chain alpha-keto acid dehydrogenase is responsible, in part, for the oxidative decarboxylation of the alpha-keto acid analog of methionine. J. Nutr . 114: 1025-1034, 1984.     

Dietary branched-chain amino acids and protein selection by rats

Consumption by rats of high protein diets is associated with elevated plasma and brain concentrations of branched-chain amino acids (BCAA). We examined the possibility that changes in BCAA concentrations in blood and brain might serve as modulators of protein consumption. After young rats had adjusted to selecting between a 10% or 25% casein diet and a 50% casein diet, a mixture of BCAA was included in the diet containing the lower amount of protein (10% + BCAA, 25% + BCAA). Supplementation of the 10% or 25% casein diets with BCAA and subsequent elevation of BCAA concentrations in plasma and brain were associated with increased selection of protein in rats given the 10% + BCAA/50% casein diet choice, but not in rats offered the 25% + BCAA/50% casein diets. When no alternative diet was available, addition of BCAA to a 15% casein diet depressed food intake, and rats given a choice between a 15% casein diet with or without added BCAA selected almost exclusively the diet without added BCAA. Although BCAA concentrations were high in plasma and brain in all experiments, concentrations of methionine, tyrosine, phenylalanine, tryptophan and histidine were low in brain in experiments in which rats altered their diet or protein selection after BCAA addition. High concentrations of BCAA in plasma and brain were not consistently associated with changes in protein selection.     

The branched-chain amino acid antagonism in chicks

The effects of dietary supplements of branched-chain amino acids on growth, food consumption and metabolism in chicks were investigated. When an adequate diet contained 1.20, 1.60, 2.25, 3.75, or 5.00% leucine, increasing leucine content caused reduced food consumption and weight gains, coupled with impaired efficiency of food utilization. When the diet deficient in branched-chain amino acids contained 0.98, 1.46, 2.25, 3.75, or 5.00% leucine, increasing leucine resulted in increased food consumption and reduced efficiency of food utilization when levels of leucine up to 3.75% were fed. Excess leucine depressed plasma concentrations of isoleucine and valine. Excesses of isoleucine or valine caused smaller depressions of concentrations of the other two branched-chain amino acids. All these effects were seen during the first 8 days of experiment, after which they diminished or disappeared. Muscle branched-chain amino acid aminotransferase (BCAT) (L-leucine:2-oxoglutarate aminotransferase, EC 2.6.1.6) activity was increased in chicks fed excess leucine but not in those fed excess isoleucine or valine. Hepatic alpha-ketoisocaproic dehydrogenase (KADH) (2-oxoisocaproate:lipoate oxidoreductase, EC 1.2.4.3) activity and muscle polyribosomal aggregation were unaffected by diet. When chicks were fed diets containing either 0.98 or 2.25% leucine, production of 14CO2 from [1-14C]isoleucine and [1-14C]valine was increased in chicks fed the higher level of leucine. The increase was small in both cases, representing approximately 2% of consumed isoleucine and valine. Increased production of 14CO2 was observed within 12 hours of feeding excess leucine; however, BCAT increased only after 2 to 4 days. No differences were seen in excreted 14C or in the relative distribution of 14C along the small intestine. We conclude that the chick is able to adapt in part to excesses of dietary leucine and that the branched-chain amino acid antagonism may involve increased catabolism of the limiting branched-chain amino acids.     

Dietary casein and soybean protein affect the concentrations of serum cholesterol, triglyceride and free amino acids in rats.

This work was undertaken to investigate the concentrations of free amino acids in blood after food was withheld from growing, male Wistar rats fed cholesterol-free, low fat (1 g corn oil/100 g) diets with casein or soybean protein for 2 wk. A diet containing 22.5 or 23.5 g/100 g of soybean protein was hypocholesterolemic compared with a diet containing 20.0 g casein/100 g diet. A comparison of serum amino acids in soybean protein-fed vs. casein-fed rats showed that, whereas concentrations of many amino acids were lower in the soybean protein-fed rats compared with the casein-fed groups, glycine was the only amino acid having a higher concentration. Further, alanine was significantly lower in the soybean protein-fed rats compared with the casein-fed rats, and the protein-induced differences in glycine and alanine concentrations of unfed rats were reproducible. When diets containing 15.0% casein or 30.0% soybean protein, a casein diet supplemented with glycine and a soybean protein diet supplemented with methionine were compared, the changes in serum glycine and alanine correlated with the changes in serum cholesterol. Concentrations of several amino acids, particularly valine, leucine and tyrosine, also changed when serum cholesterol concentrations varied, but these effects could not be explained by our experiments. The results suggest that a change in serum concentration of glycine and alanine of unfed rats may be related to the change in serum cholesterol concentration.     

Dietary disproportions of amino acids in the rat: effects on food intake, plasma and brain amino acids and brain serotonin.

Food intake, growth, plasma and brain amino acid, and brain serotonin and 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations were measured in rats fed low protein diets containing disproportionate amounts of large neutral amino acids (LNAA) devoid of tryptophan or histidine (tryptophan or histidine imbalance). Five-day food intakes and weight gains of rats fed the imbalanced diets were depressed. The concentration of the limiting amino acid was low in brains of rats fed diets containing LNAA that compete with either tryptophan or histidine for entry into brain. Correlations were observed between the brain concentrations of most individual LNAA and either the ratios of the plasma concentration of that LNAA to the sum of the other LNAA, or the predicted rates of influx of that LNAA. Cumulative food intakes were correlated with brain concentrations of the limiting amino acid, tryptophan or histidine. Food intakes were not consistently correlated with concentrations of serotonin and 5-HIAA because these compounds were altered only in brains of rats in the tryptophan study. Competition among amino acids for uptake into brain appears to be involved in the feeding response of the rat to dietary disproportions of amino acids, but this response is not directly related to changes in brain concentrations of serotonin and 5-HIAA.