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Biomedical subjects

S A Adibi

Publications and source records attributed to S A Adibi.

At least 109 records · Page 6Linked to original sources
PubMed1977

Effect of nephrectomy and enterectomy on plasma clearance of intravenously administered dipeptides in rats.

1. Sham-operated and bilaterally nephrectomized rats were injected intravenously with glycyl-L-leucine, glycylglycine and glycylsarcosine, and the concentrations of these dipeptides in plasma and muscle, liver, renal cortex (in the sham-operated rats) and intestinal mucosa at various intervals were determined. 2. Initially the plasma concentrations of glycyl-leucine and glycylglycine were higher in nephrectomized than in control rats but later the concentrations were similar in both groups of rats. The disappearance of these two dipeptides from plasma was almost complete within 20 min, and their plasma half-lives were not changed remarkably by nephrectomy. In contrast, nephrectomy markedly impaired disappearance of glycylsarcosine from plasma and prolonged its half-life from 7-6 min to 52-0 min. 3. Glycyl-leucine and glycylglycine were not detected in tissues of control rats injected with these dipeptides, but glycylsarcosine was recovered from all four tissues examined. Nephrectomy resulted in greater accumulations of glycylsarcosine in tissues and the appearance of glycylglycine in the remaining three tissues and glycyl-leucine in muscle. 4. Enterectomy did not have a remarkable effect on plasma half-life of glycylglycine but it allowed recovery of this dipeptide from renal cortex, liver and muscle. 5. It is concluded that kidneys amd small intestine are involved in the disposition of circulating dipeptides, but in their absence other tissues may assume a greater role in this regard. However, renal clearance appears to be an important route for the disposition of dipeptides which are poorly hydrolysed by body tissues.

Animals↗
PubMed1977

Cytoplasmic dipeptidase activities of kidney, ileum, jejunum, liver, muscle, and blood.

Peptide hydrolase activities against glycyl-L-leucine and glycylglycine were investigated in the soluble fractions of blood, liver, kidney cortex, skeletal muscle (gastrocnemius), and jejunal and ileal mucosa of rats. The maximal hydrolase activity in each tissue was determined when the incubation conditions, such as time, pH, substrate and enzyme concentrations, and ionic requirements were optimal. The kinetic constants (apparent Km and Vmax) were determined from Lineweaver-Burk double reciprocal graphs. Maximal hydrolysis rates against both dipeptides were many times greater by kidney and intestinal segments than by those of muscle, liver, or blood. The order of Vmax for hydrolase activity against glycylleucine was kidney greater than ileum greater than jejunum greater than liver greater than muscle greater than blood, and the order against glycylglycine was ileum greater than kidney greater than jejunum greater than liver greater than muscle. Those tissues that had the lowest Vmax values (liver and muscle), when calculated on the basis of tissue weights, were shown to have activities comparable to the others. Results of this study are consistent with our previous findings that: 1) glycylleucine half-life in plasma is shorter than that of glycylglycine, and 2) disappearance rates of these dipeptides from plasma are not affected by nephrectomy or enterectomy.

Animals↗
PubMed1977

The number of glycine residues which limits intact absorption of glycine oligopeptides in human jejunum.

Studies were performed to determine whether glycine peptides of four or more glycine residues can be transported by the peptide carrier system, previously shown to transport diglycine and triglycine. When human jejunum was perfused with tetraglycine solutions, the rate of tetraglycine disappearance increased linearly as the concentration was increased over the range of 12.5-50 mM, however, the rate was slow in comparison to diglycine and triglycine disappearance rates.Glycylleucine, a competitive inhibitor of diglycine and triglycine transport, was without effect on the disappearance rate of tetraglycine, but increased (over sixfold) appearance rates of triglycine and diglycine (products of tetraglycine hydrolysis). These products were the results of hydrolysis of tetraglycine by the brush border enzymes because cytosol fraction lacked any hydrolase activity against tetraglycine. When a jejunal ring preparation was incubated with tetraglycine, there was intracellular accumulation of diglycine and triglycine but not of tetraglycine. The rates of glycine uptake were always markedly greater from diglycine and triglycine solutions than from corresponding glycine or tetraglycine solutions; rates of glycine uptake from tetraglycine solutions were either similar to or greater than rates from glycine solutions, depending on the infusion concentration. When the number of glycine residues was increased to hexaglycine, the phenomenon of a greater rate of glycine uptake from a peptide versus a free amino acid solution was no longer apparent. In vitro assay of peptide hydrolase activity of the luminal fluid revealed no activity against diglycine and triglycine and only trace activities against tetraglycine, pentaglycine, and hexaglycine. THE ABOVE OBSERVATIONS SUGGEST THE FOLLOWING CONCLUSIONS: (a) the disappearance of tetraglycine in the human jejunum is accomplished principally by hydrolysis by brush border oligopeptidases; (b) the rate limiting step in the uptake of glycine from tetraglycine or higher peptides is due to hydrolysis of these peptides to absorbable products.

Adult↗
PubMed1976

Metabolism of branched-chain amino acids in altered nutrition.

Plasma concentrations of the branched-chain amino acids (leucine, isoleucine, and valine) are more prominently affected than the concentrations of other amino acids by changes in dietary-caloric, protein, fat, and carbohydrate-intake in man. For example, within a day of starvation or protein deprivation, there are increases or decreases, respectively, in concentrations of these amino acids in the plasma of healthy human volunteers. The cellular mechanisms of these changes have been investigated in rats, since the changes in the plasma branched-chain amino acid concentrations in response to the previously stated dietary alterations are similar to those found in man. Among the tissues studied (liver, skeletal muscle, heart, kidney, and intestine) only liver and the skeletal muscle exhibit changes in branched-chain amino acid concentrations in response to dietary alteation. Changes in plasma concentrations appear to reflect more intimately those of the muscle than theliver. After 8 days of starvation, there is a 25% decrease in the muscle protein, but after 8 days of protein deprivation, there is no significant change in the muscle mass. Increases in concentrations of branched-chain amino acids in the muscle are much smaller than the amounts of these amino acids lost as protein constituents form the muscle during fasting. Changes in tissue transport, transamination, oxidation, or metabolic conversions of branched-chain amino acids in tissues. It is concluded that increased muscle protein breakdown, which provides substrates for enhanced gluconeogenesis in the liver and enhanced branched-chain amino acid oxidation in the muscle, is the major mechanism of hyperbranched-chain aminoacdemia in starvation. On the other hand, the principal factors in the development of hypobranched-chain aminoacidemia during protein deprivation are absence of exogenous amino acids as well as curtailed muscle protein breakdown.

Alanine↗
PubMed1976

Assessment of effect of starvation, glucose, fatty acids and hormones on alpha-decarboxylation of leucine in skeletal muscle of rat.

The present investigations of rates of oxidation of [U-14C] or [1-14C]leucine by homogenates of gastrocnemius muscle of fed and starved rats have indicated that 14CO2 production is mainly the result of alpha-decarboxylation of leucine in this tissue. This incomplete oxidation was not the result of imparied tricarboxylic acid cycle since the oxidation of palmitate proceeded to completion within the experimental conditions. In the subsequent studies, the effect of altered nutrition and metabolic factors on alpha-decarboxylation of leucine by gastrocnemius muscle homogenates was investigated. Starvation increased the rate of alpha-decarboxylation of leucine. Glucose or palmitate (C16) added in physiological concentrations to the incubation medium were without effect on decarboxylation of leucine, but this reaction was stimulated by addition of 1 mM hexanoate (C6) or octanoate (C8) to the incubation medium. However, when fatty acid chain length was elongated to C10 (decanoate), the stimulatory effect was not only abolished, but this fatty acid significantly inhibited the rate of leucine decarboxylation. Addition of insulin, epinephrine, glucagon and cyclic AMP within a wide range of concentrations to the incubation medium did not significantly affect the rate of decarboxylation of leucine. These studies indicate a complex interrelationship between the metabolism of leucine and that of fatty acids.

Animals↗
PubMed1976

Dietary regulation of liver and muscle transport of amino acid.

Distribution ratios (intracellular concn/extracellular concn) of alpha-amino isobutyric acid (AIB) after intravenous injection were determined in fed, 12-h, 1-day, and 5-day starved rats. Progressive increases (over fourfold) in the distribution ratios of AIB in the liver and progressive decreases (over threefold) in the gastrocnemius muscle occurred within these periods. On full day of protein deprivation was without effect on AIB distribution ratios, but after 5 days it produced an increased distribution ratio of AIB in the liver (twofold), without affecting that of the muscle. A sudden increase in hepatic glucose output, induced by phlorizin, was followed by an increase in the liver distribution ratio of AIB. In starvation the increase in plasma concentration of glucagon and decrease in insulin level preceded the changes in AIB distribution ratios; in protein deprivation there was no change in plasma concentrations of these hormones. It is concluded that caloric restriction profoundly affects amino acid transport by the liver and by the skeletal muscle. These transport changes would enhance the availability of substrates for increased gluconeogenesis during starvation.

Aminoisobutyric Acids↗
PubMed1976

Peptide absorption.

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Amino Acid Sequence↗
PubMed1976

Absorptive and digestive function of the jejunum after jejunoileal bypass for treatment of human obesity.

Rates of absorption of leucine, glycylleucine, and glucose, and rates of hydrolysis of maltose were determined in the jejunum of a group of obese persons before and at intervals (between 2 and 20 montsh) after jejunoileal bypass for the treatment of obesity. The leucine absorption rate was significantly reduced after the bypass, but the absorption rates of glycylleucine and glucose as well as the hydrolysis rate of maltose were unchanged. Light microscopic investigation of the jejunal mucosa, obtained by a peroral biopsy technique before and at 7 months after by bypass operation, did not reveal any change in the histological appearance of this tissue. The plasma aminograms of all 7 patients were compared before and at intervals after the bypass operation; all exhibited a constant pattern of change that was characterized by significant decreases in the concentrations of serine and glycine and by significant decreases in the concentrations of valine, isoleucine, leucine, tyrosine, and phenylalanine. This pattern of change, which is characteristic of protein depletion, persisted during the entire period of observation. Two of these 7 patients developed laboratory evidence of hepatic dysfunction. It is concluded that (1) protein depletion is common to all patients with jejunoileal bypass with or without hepatic dysfunction; and (2) protein depletion results in a sustained reduction in free amino acid absorption in the jejunum.

Adult↗
PubMed1975

Modulation of leucine transaminase activity by dietary means.

The specific activity of leucine transaminase was measured in supernatants of liver, skeletal muscle (gastrocnemius), and kidney homogenates obtained from fed, starved, and protein-deprived rats. After 12 h of starvation, there were slight reductions in leucine transaminase activity of both muscle and kidney tissues. When starvation was prolonged to 1 full day, the activity of this enzyme increased by approximately twofold in both muscle and kidney. Prolongation of fasting to 5 days resulted in an additional increase in specific activity of leucine transaminase in muscle. During the entire 5 days of starvation, leucine transaminase activity remained unaltered in liver of starved rats. Protein deprivation for 1 or 5 days resulted in significant reductions in specific activity of leucine transaminase in skeletal muscle. Protein deprivation did not produce a remarkable effect on the activity of this enzyme in kidney or liver tissue. The results of this study, together with those previously obtained, indicate that within our experimental conditions increased oxidation of leucine in skeletal muscle of starved rats is not initially related to an alteration in activity of leucine transaminase. When caloric deficiency is prolonged, the potential for transamination is also increased. These adaptive changes increase the ability of skeletal muscle to use leucine as a metabolic fuel.

Animals↗
PubMed1975

Evidence for two different modes of tripeptide disappearance in human intestine. Uptake by peptide carrier systems and hydrolysis by peptide hydrolases.

The intestinal fate of two tripeptides (triglycine and trileucine), which differ markedly in solubility and molecular weight, have been investigated by jejunal perfusion in healthy human volunteers. Rates of glycine or leucine uptake from test solutions containing triglycine or trileucine were greater than from test solutions containing corresponding amounts of free glycine or free leucine, respectively. The rate of glycine uptake from a 100 mM triglycine solution was greater than that from a 150 mM diglycine solution. At each infused load of triglycine (e.g., 1,000 mumol/min) the rates (micromoles/minutes per 30 cm) of either triglycine disappearance (810 +/- 40) or glycine absorption (2,208 +/- 122) were markedly greater than the luminal accumulation rates of either diglycine (56 +/- 10) or free glycine (110 +/- 18). The luminal accumulation rate of free leucine during infusion of a 5 mM trileucine solution was over threefold greater than that of free glycine during the infusion of a 5 mM triglycine solution. Luminal fluid exhibited no hydrolytic activity against triglycine, but contained some activity against trileucine. Saturation of free amino acid carrier system with a large load of leucine did not affect glycine absorption rate from a triglycine test solution, but isoleucine markedly inhibited the uptake from a trileucine solution. When the carrier system for dipeptides was saturated with a large amount of glycylleucine, the disappearance rate of triglycine was considerably reduced while that of trileucine remained unaffected. After addition of glycylleucine to tripeptide solutions, there was a minimal increase in the luminal accumulation of diglycine, while dileucine accumulation was incresed by 62-fold.

Biological Transport↗
PubMed1975

Role of insulin and glucose in the induction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients.

It is generally assumed, but not established, that the lowering of plasma free amino acid levels following glucose intake is entirely mediated by stimulated insulin secretion. This problem was investigated in groups of healthy volunteer subjects, juvenile diabetics, and insuloma patients. The plasma concentrations of 15 individual free amino acids, glucose, and insulin or C-peptide were determined before and at intervals after either oral glucose (75 Gm.) or intravenous glucose (0.25 Gm. per kilogram of body weight) or tolbutamide (1 Gm.). Glucose lowered plasma amino acid levels in both situations of stimulated (healthy volunteer subjects) and absent (diabetic) insulin secretion. The lack of insulin response in juvenile diabetics was evident by the lack of any significant increase in C-peptide levels following glucose ingestion. Nevertheless, despite markedly greater plasma glucose levels, hypoaminoacidemia was less severe in diabetics than in normal volunteer subjects. In comparison to healthy volunteer subjects who showed significant decreases in concentrations of 14 of 15 examined amino acids by glucose, the diabetic individuals exhibited significant decreases in concentration of 8 amino acids (leucine, isoleucine, valine, tyrosine, phenylalanine, methionine, citrulline, and arginine). In face of a massively greater insulin response in an insuloma patient (greater than 1,000 muU per milliliter), the decreases in the levels of individual free amino acids following glucose were within the range of values obtained in the normal volunteer subjects. The stimulation of insulin secretion with tolbutamide also lowered the concentrations of free amino acids in plasma. However, one importnat difference distinguished the effect of tolbutamide from that of glucose. Within a few minutes after the injection of tolbutamide, there was a marked and persistent fall in alanine levels, while during the entire course of the glucose tolerance test there were no significant changes in the level of this amino acid, suggesting a difference in the mechanism of hypoaminoacidemia induced by endogenous insulin in the presence or absence of exogenous glucose. Despite a markedly greater insulin response to tolbutamide in the insuloma patient (greater than 1,500 muU per milliliter), the decreases in plasma glucose and free amino acid levels fell within the range of values obtained in normal volunteer subjects. In conclusion, the exogenous glucose per se lowers the levels of free amino acids in plasma. This effect is enhanced by insulin.

Adenoma, Islet Cell↗
PubMed1974

Functional characterization of dipeptide transport system in human jejunum.

The present studies were performed to determine whether dipeptide absorption in human jejunum exhibits the characteristics of carrier-mediated transport. 15-cm jejunal segments from human volunteers were perfused with test solutions containing varying amounts of either glycylglycine, glycylleucine, glycine, leucine, glycylglycine with leucine or glycine, glycylglycine with glycylleucine, or glycylleucine with an equimolar mixture of free glycine and leucine. Jejunal absorption rates of both glycylglycine and glycylleucine followed the kinetics of a saturable process. The K(m) value in millimoles/liter of glycylglycine was significantly greater than the K(m) value of glycylleucine (43.3+/-2.6 vs. 26.8+/-5.9, P < 0.05); and the K(m) value of glycine was also significantly greater than the K(m) value of leucine (42.7+/-7.5 vs. 20.4+/-5.4, P < 0.05). While overlapping occurred among the K(m) values of free amino acids and dipeptides, the transport kinetics of dipeptides were characterized by higher V(max) values (in micromoles per minute per 15 centimeters) than those of free amino acids. For example, the V(max) values for glycylglycine and glycine were 837+/-62 and 590+/-56, respectively (P < 0.02). While jejunal absorption rates of glycylglycine were not significantly affected by free leucine or free glycine, they were competitively inhibited by glycylleucine. The jejunal absorption rate of glycylleucine was not significantly altered by an equimolar mixture of free glycine and leucine. The selective absorption of dipeptides was investigated by infusing three equimolar mixtures, each containing two different dipeptides. Among the three dipeptides examined, glycylglycine was the least absorbed. There was no significant difference between the absorption of glycylleucine and leucylglycine. The above studies suggest that absorption of both glycylglycine and glycylleucine is mediated by a carrier which is not shared with free neutral amino acids; and that both COOH- and NH(2)-terminal amino acids appear to be influential in imposing the affinity of a dipeptide for the absorption sites.

Biological Transport↗