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Biomedical subjects

A E Harper

Publications and source records attributed to A E Harper.

At least 37 records · Page 2Linked to original sources
PubMed1990

Norleucine: a branched-chain amino acid analog affecting feeding behavior of rats.

Norleucine, an isomer of leucine and isoleucine and a potent competitor of large neutral amino acid transport into brain, thereby depleting certain amino acid pools, was tested for its effects on growth and feeding behavior of rats fed an amino acid diet limiting in leucine. Growth and food intake were depressed in proportion to the dietary level of norleucine (0.2 to 1.1% of the diet). With suboptimal amounts of indispensable amino acids, leucine at 150% of the requirement reversed the effects of 0.2 and 0.5% norleucine; slight excesses of the other indispensable amino acids were required with extra leucine for maximum growth with 1.1% norleucine. Rats almost exclusively preferred the control to the norleucine diet, but not if the latter diet also contained leucine. Rats also strongly selected a nonprotein rather than norleucine diet when this was the first available choice. If the first choice was between the nonprotein and control diets, rats later almost exclusively selected the norleucine-containing rather than the nonprotein diet for varying periods (2 to 6 days). These studies suggest that amino acid analogs may be useful agents in the study of animal behavior associated with changes in brain amino acid pools.

Amino Acids↗
PubMed1990

Phylogenetic comparisons of the branched-chain alpha-ketoacid dehydrogenase complex.

1. Antibodies against the E1b and E2b components of bovine branched-chain alpha-ketoacid (BCKA) dehydrogenase (BCKAD) complex completely inhibited BCKA oxidation in mammalian and avian mitochondria. BCKA oxidation by salmonid mitochondria was less affected and the enzyme from Pseudomonas putida was unaffected. 2. In rodents, anti-E1b E2b IgG inhibited oxidation of all three BCKA in a similar dose-dependent manner: oxidation of alpha-ketobutyrate and alpha-keto-y-methiolbutyrate was also partially inhibited. 3. Except for the salmonid BCKAD, a similar Mr for the E2b and E1b alpha proteins was observed in these species. 4. After digestion with V-8 protease similar immunoreactive peptides were observed for the human and rodent complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1990

High branched-chain alpha-keto acid intake, branched-chain alpha-keto acid dehydrogenase activity, and plasma and brain amino acid and plasma keto acid concentrations in rats.

Diets containing high quantities of individual branched-chain alpha-keto acids (BCKAs) or a combination of BCKAs as used for treatment of renal disease were fed to rats. When the diet contained a single BCKA, its concentration was high in plasma and the concentration of its corresponding amino acid was high in plasma and brain. Liver BCKA dehydrogenase (BCKD) was 42% active in control rats. Consumption of diets containing 0.38 mol/kg diet of alpha-ketoisocaproate (KIC), alpha-keto-beta-methylvalerate (KMV), or alpha-ketoisovalerate (KIV) resulted in complete activation of liver BCKD. Consumption of the diet containing the combination of BCKAs increased basal BCKD activity of liver twofold. Muscle BCKD was activated after feeding the KIV diet (2-fold), the KIC diet (3-fold), and the KMV diet (15-fold). Total BCKD activity of liver and muscle was unaffected by dietary treatments. Activation of liver and muscle BCKD by dietary BCKA is consistent with their ability to inhibit BCKD kinase in vitro.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1990

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.

Amino Acids↗
PubMed1990

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.

Amino Acids↗
PubMed1990

Sucrose and delinquency: oral sucrose tolerance test and nutritional assessment.

Claims that juvenile delinquency may be associated with reactive hypoglycemia or nutritional deficiencies have received widespread attention but little objective evaluation. To assess the validity of these claims, nutritional and psychological indices of juvenile delinquents have been measured. Serum glucose and insulin profiles during an oral sucrose tolerance test were measured in 137 delinquent and 41 nondelinquent male adolescents aged 14 to 19. In addition, nutritional status of both populations was assessed by anthropometry (height, weight, arm circumference, triceps skin fold) and biochemical measures (hematocrit, red-blood cell thiamin, and serum copper, ferritin, and zinc). Delinquent subjects had slightly but significantly lower serum glucose values at four of six time points (fasting, 60 minutes, 120 minutes, 180 minutes) and higher serum insulin values at one time point (30 minutes) compared with nondelinquent subjects. Changes in glucose from fasting levels indicate that these subjects were regulating serum glucose adequately, but doing so at lower values; changes in insulin from fasting levels indicate that black delinquents initially secreted more insulin than either white subject group. There were no significant associations between excursions in serum glucose or insulin and any adrenergic signs or symptoms of low blood glucose levels. Nutritional status of incarcerated delinquents did not differ from that of nonincarcerated subjects on most measures. Although the significantly lower serum glucose levels and higher serum insulin levels are intriguing, no support is offered by results of this study for allegations that sucrose ingestion causes reactive hypoglycemia in juvenile delinquents or that delinquent male adolescents are at greater risk nutritionally than male adolescents of the same age who are not delinquent.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Sucrose and delinquency: behavioral assessment.

In this study, a double-blind challenge design was used to evaluate the hypothesis that sucrose ingestion may compromise the behavioral performance of juvenile delinquents. Subjects were 58 white delinquents, 57 black delinquents, and 39 white nondelinquents. The behavioral assessment included tasks that are relevant to delinquency and that might be expected to be disrupted following sucrose ingestion. The results provide no evidence that sucrose ingestion impairs the performance of juvenile delinquents. In fact, the results of several analyses indicated that the sucrose breakfast was associated with improved performance. In additional analyses the effect of sucrose on particular subgroups of juvenile delinquents was evaluated. Statistical interactions indicated that the performance of delinquents rated as more behaviorally disturbed benefited from sucrose ingestion, whereas those delinquents with less pronounced behavior problems tended to show impaired performance following a sucrose-loaded breakfast. These results indicate that simple statements regarding the effects of sucrose ingestion on behavior are likely to be misleading and highlight the need to consider individual difference variables when investigating the effects of sucrose on juvenile delinquents.

Adolescent↗
PubMed1989

Protein intake, brain amino acid and serotonin concentrations and protein self-selection.

Analysis of evidence of associations among dietary protein content, brain amino acid and serotonin concentrations, and protein self-selection by rats suggests that 1) protein intake is not regulated precisely, although rats will select between low and high protein diets to obtain an adequate, but not excessive, amount of protein; 2) associations between brain serotonin concentration and protein intake are weak, although consumption of single meals of protein-deficient diets will elevate brain serotonin concentration; 3) the nature of signals that drive rats to avoid diets containing inadequate or excessive amounts of protein remains obscure; (4) whole brain amino acid and serotonin concentrations are quite stable over the usual range of protein intakes, owing to competition among amino acids for uptake across the blood-brain barrier and effective metabolic regulation of blood amino acid concentrations; 5) protein intake and preference are not in themselves regulated, but what appears to be regulation of intake and preference is a reflection of the responses of systems for control of plasma amino acid concentrations; and (6) the relative stability of the average protein intake of groups of self-selecting rats (which gives the appearance of regulation) results from averaging the variable behavioral responses--learned aversions and preferences--of rats to the variety of sensory cues arising from diets that differ in protein content.

Amino Acids↗
PubMed1989

Activities of branched-chain amino acid--degrading enzymes in liver from rats fed different dietary levels of protein.

The relationships among dietary protein intake, plasma branched-chain amino acid (BCAA) and keto acid (BCKA) concentrations, and liver BCAA-degrading enzyme activities were investigated in rats fed, for 5 h/d for 2, 6 or 9 d, diets containing from 0 to 50% casein. Plasma, liver and muscle BCAA concentrations were proportional to protein intake over the entire range tested; plasma BCKA concentration, however, was proportional only in the range from 0 to 20% casein, after which a plateau was reached. By d 2, liver cytosolic BCAA aminotransferase activity had increased in rats fed 50% casein; by d 9, activity had increased in rats fed 0 or 5% casein as well. Liver mitochondrial BCAA aminotransferase activity was unresponsive to dietary treatment. Basal liver BCKA dehydrogenase activity and the percent active complex were proportional to protein intake on d 2 and 6. On d 2, total BCKA dehydrogenase activity was the same in all groups; by d 6, total activity had increased in rats fed 30 or 50% casein. We conclude that although the adaptive changes in BCAA-degrading enzyme activities are small, they are sufficient to compensate for excessively high or low protein intakes, so that tolerable concentrations of BCAA and BCKA are maintained.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1989

Distribution of alpha-aminoisobutyric acid in tissues of lean and genetically obese mice.

Distribution of tracer amounts of the nonmetabolizable neutral amino acid alpha-[1-14C]aminoisobutyric acid (AIB) between blood and several tissues was measured in lean and ob/ob mice over an 8-hr period. As AIB was injected on the basis of body weight and as ob/ob mice have a relatively low blood volume, absolute concentrations of AIB in blood and tissues were almost always higher in the obese than the lean mice. However, the ratio of AIB concentration in the tissues to that in the blood was clearly higher in skeletal muscle, diaphragm, and brain, and possibly higher in liver of the lean than of the obese animals. Ratios in heart were similar. The results suggest that lean and genetically obese mice differ in their capacity to transport amino acids between blood and various tissues.

Aminoisobutyric Acids↗
PubMed1988

Effects of dietary protein intake on branched-chain keto acid dehydrogenase activity of the rat. Immunochemical analysis of the enzyme complex.

Polyclonal antibodies directed against the dihydrolipoyl transacylase (E2) and alpha subunit of branched-chain alpha-keto acid decarboxylase (E1 alpha) components of the bovine branched-chain keto acid dehydrogenase complex were shown to cross-react with the E2 and E1 alpha polypeptides of the enzyme complex of different rat tissues. Phosphorylation of the branched-chain keto acid dehydrogenase complex resulted in inhibition of enzyme activity concomitant with phosphate incorporation into the E1 alpha polypeptide. Phosphorylation of E1 alpha slowed its rate of migration through sodium dodecyl sulfate-polyacrylamide gels. This permitted resolution of the phosphorylated and unphosphorylated forms of E1 alpha on immunoblots. Liver and skeletal muscle mitochondria were prepared from rats consuming 6, 20, or 50% casein diets. The enzyme complex in mitochondria was measured by radioisotopic enzyme assay and immunoassay. Liver branched-chain keto acid dehydrogenase was 25% active in rats consuming 6% casein diets; whereas in rats consuming 20 or 50% casein diets, the liver enzyme was 82 or 100% active, respectively. Branched-chain keto acid dehydrogenase of muscle was 10, 13, and 22% active, respectively, in rats consuming 6, 20, and 50% casein diets. The amount of protein consumed by rats did not affect the total amount of the enzyme complex per unit of mitochondrial protein as measured by either the radioisotopic assay (enzyme activity) or the immunoassay. However, the protein intake of rats did affect activity of the enzyme kinase in liver. Liver branched-chain keto acid dehydrogenase kinase was more active in rats consuming 6% casein than in those fed chow or 50% casein diets. The amount of protein consumed by rats thus influences the enzyme activity in liver and muscle by affecting the reversible phosphorylation mechanism and not by induction of branched-chain keto acid dehydrogenase.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1988

Induction of conditioned taste aversion in rats by GABA or other amino acids.

GABA included in the diet is known to reduce food intake and growth of rats fed a low protein diet. Experiments were designed to determine if GABA or other small neutral amino acids would affect food intake if they were administered separately from the diet, and if such amino acids could induce a conditioned taste aversion (CTA) to saccharin. Intubated or injected GABA or alpha-aminoisobutyric acid (AIB), a non-metabolizable isomer of GABA, reduced food intake. When rats were fed a low protein diet, IP injection of threonine (2 mmoles/200 g rat) induced CTA but did not depress food intake; serine (3 mmoles/200 g rat) induced CTA and caused only a small reduction in food intake. Another isomer, alpha-amino-n-butyric acid did not affect food intake or induce CTA at the tested concentrations. Adaptation to a high protein diet, which increases enzymatic degradation of many amino acids including GABA and serine, lessened severity of GABA-induced CTA and eliminated that caused by serine. CTA to saccharin can be induced by certain amino acids; the mechanism is unknown but may involve malaise or other adverse sensations.

Amino Acids↗
PubMed1988

Influence of dietary leucine content on the activities of branched-chain amino acid aminotransferase (EC 2.6.1.42) and branched-chain alpha-keto acid dehydrogenase (EC 1.2.4.4) complex in tissues of preruminant lambs.

1. Branched-chain amino acid aminotransferase (EC 2.6.1.42; BCAAT) and branched-chain alpha-keto acid dehydrogenase (EC 1.2.4.4; BCKDH) activities were measured preruminant lamb liver, longissimus dorsi muscle, kidney, jejunum and adipose tissue, 2 h after a meal with or without an excess of leucine. 2. Skeletal muscle contained about 70% of the total basal BCAAT activities of the tissues studied whereas liver contained about 60% of the total BCKDH activities of these tissues. 3. BCAAT activities were very low in preruminant lamb tissues. BCKDH was more phosphorylated in tissues of preruminant lambs than in rats, especially in liver. These low catalytic potentialities might contribute to a low rate of branched-chain amino acid catabolism in sheep. 4. Ingestion of an excess of leucine led to an increase in liver and jejunum BCAAT activities and activation of BCKDH in jejunum.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1988

Dietary amino acid analogues and transport of lysine or valine across the blood-brain barrier in rats.

Studies were undertaken to determine if dietary disproportions of amino acids would alter flux into brain of the amino acid present in the diet in a growth-limiting concentration. Rats were adapted to a lysine-limiting diet before receiving a meal of this control diet, alone or with added lysine or homoarginine (a competitor for lysine transport) or both, before intravenous infusion of [14C]lysine. The brain-to-plasma radioactivity ratio was lower in rats fed extra lysine or homoarginine than in rats fed the control diet, whereas lysine flux and brain lysine concentration were high in rats fed extra lysine alone. Flux and concentration were lower in rats fed homoarginine + lysine than in rats fed extra lysine alone. Other rats were fed a valine-limiting diet containing added valine, norleucine (a competitor for valine transport) or both, before [14C]valine was infused. Valine flux and brain valine concentrations were higher in rats fed extra valine than in control rats, whereas flux was lower in the group fed norleucine alone. Valine flux was higher in rats fed norleucine + valine than in the rats fed norleucine alone. Our studies show that dietary disproportions of amino acids can alter the flux of specific amino acids across the blood-brain barrier.

Aminocaproates↗