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Biomedical subjects

S A Adibi

Publications and source records attributed to S A Adibi.

At least 91 records · Page 5Linked to original sources
PubMed1982

Effect of exercise on rates of oxidation, turnover, and plasma clearance of leucine in human subjects.

We have previously hypothesized that increased muscle oxidation of leucine in starvation is an adaptive response to fuel deficiency in this tissue. To investigate this hypothesis further, we have measured the rates of oxidation, turnover, and plasma clearance of [1-14C]leucine in six obese subjects at rest and during 2 h of mild leg exercise. This experimental design was based on the fact that exercise has the greatest impact on energy expenditure in muscle, the principal site for leucine oxidation. Exercise produced a fourfold increase in oxygen consumption. The rate of alpha-decarboxylation of leucine was increased twofold by leg exercise, whereas there were modest decreases (13%) in the rates of turnover and plasma clearance of this amino acid. The plasma concentrations of lactate and alanine increased twofold during exercise, but plasma concentrations of leucine and other amino acids, glucose, beta-hydroxybutyrate, and insulin remained unaltered. Our data suggest that during exercise oxidation of leucine as an energy source increases, whereas the utilization of this amino acid as a substrate for protein synthesis decreases.

Amino Acids↗
PubMed1982

Enrichment of glycine pool in plasma and tissues by glycine, di-, tri-, and tetraglycine.

Very little information is available on metabolism of oligopeptides in vivo. The present studies were performed to investigate the metabolic fate of diglycine, triglycine, and tetraglycine when injected into a central vein in rats. These peptides disappeared rapidly from plasma without any significant loss in urine. Plasma and tissue concentrations of glycine were measured when the same amount of glycine was injected in free or peptide form. Two minutes after the injection of glycine (1.l0 mumol/g body wt), there was over a tenfold increase in plasma glycine concentration. This increase was diminished when diglycine instead of glycine was injected. Each increase in the number of glycine residues resulted in further reduction in the initial rise in plasma glycine concentration was increased by each injection. This was more pronounced in the kidney than in the liver. Injection of triglycine and tetraglycine resulted in greater glycine concentration in the kidney than injection of either glycine or diglycine. Furthermore, unlike liver and muscle, each increase in the number of glycine residues resulted in greater recovery of glycine peptides from the kidney. These results suggest that with each increase in the number of glycine residues a greater amount of injected glycine peptide is taken up by the kidney for hydrolysis to glycine.

Animals↗
PubMed1982

Stimulation of gastric acid secreted by glycine and related oligopeptides in humans.

To investigate the effect of oligopeptides on gastric secretion in humans, we investigated acid secretion in healthy volunteers after the intragastric infusion of physiological saline, glycine (100 mM), diglycine (50 mM), triglycine (33 mM), and tetraglycine (25 mM). All test solutions were equivalent in glycine content, osmolality (300 mosmol), and pH (5.5). Although the rate of acid secretion was greater during glycine than saline infusion [5.6 +/- 0.8 vs. 3.3 +/- 1.1 mmol/h (means +/- SE); P less than 0.05], the rate of acid secretion during glycine infusion was not significantly different from that induced by its related peptides. There were increases in plasma glycine concentration during infusion of glycine and its related peptides but no detectable changes in serum gastrin levels. The increases in plasma glycine must have been due to absorption from the small intestine because there was no gastric absorption of glycine in free or dipeptide form nor diglycine hydrolysis in the stomach. Therefore, our results permit implicating only the increased plasma glycine concentrations as the stimulus for acid secretion by glycine and its homologous peptides.

Adult↗
PubMed1980

Leucine oxidation and protein turnover in clofibrate-induced muscle protein degradation in rats.

Treatment of hyperlipidemia with clofibrate may result in development of a muscular syndrome. Our previous investigation (1979. J. Clin. Invest.64: 405.) showed that chronic administration of clofibrate to rats causes myotonia and decreases glucose and fatty acid oxidation and total protein of skeletal muscle. In the present experiments we have investigated amino acid and protein metabolism in these rats. Clofibrate administration decreased the concentration of all three branched-chain amino acids without affecting those of others in muscle. Studies to examine the mechanism of decreases in muscle concentrations of branched-chain amino acids showed the following: (a) Plasma concentration of leucine was decreased, whereas there was no significant change in the concentration of isoleucine and valine. (b) Liver concentrations of all three branched-chain amino acids remained unaltered. (c) The uptake of cycloleucine (a nonmetabolizable analogue of leucine) by both muscle and liver was unaffected. (d) The percentage of a trace amount of injected [1-(14)C]leucine expired as (14)CO(2) in 1 h was significantly increased. (e) The capacity of muscle homogenate for alpha-decarboxylation of leucine was enhanced, whereas that of liver was unaffected. (f) The activity of leucine transaminase was unaffected, whereas that of alpha-ketoisocaproate dehydrogenase was increased in muscle. Studies of protein synthesis, carried out as incorporation of leucine into protein and corrected for differences in specific activity, showed no alteration in liver but enhanced synthesis in muscle of clofibrate-fed rats. Clofibrate stimulated muscle protein degradation, which was demonstrated by increased tyrosine release from gastrocnemius muscle slices and by increased urinary excretion of 3-methylhistidine. We conclude that (a) clofibrate treatment increased branched-chain amino acid oxidation by increasing the activity of branched-chain alpha-ketoacid dehydrogenase in the muscle, (b) increased oxidation results in selective decreases in the concentration of these amino acids in muscle, and (c) decreases in branched-chain amino acid concentration may be responsible for increased protein degradation in muscle.

Administration, Oral↗
PubMed1979

Involvement of transverse tubules in induced myotonia.

A single oral dose of clofibrate (30 mg/100 gm body weight) given to 250-300 gm male rats produced myotonic discharges from both the gastrocnemius and soleus muscles 2 hours after feeding. Rats fed the same dosage for 14 consecutive days exhibited electromyographic discharges consistent with profound myotonia. Fibers removed from the superficial region of the gastrocnemius muscle served as the source of fast twitch fibers for histological studies. Slow twitch fibers were observed in the soleus muscle. After a single clofibrate feeding localized T-tubule dilation was observed in a small percentage of myofibers in both muscles. In rats fed clofibrate for 14 days, approximately 30% of the fibers of the gastrocnemius and soleus muscles had dilated T-tubules. The motochondria of the soleus muscles of these rats were characterized by dilated intercristal matrixes containing electron densities. No mitochondrial changes were observed in the fibers of the gastrocnemius muscles taken from the same rats.

Action Potentials↗
PubMed1979

Paradoxical effects of clofibrate on liver and muscle metabolism in rats. Induction of myotonia and alteration of fatty acid and glucose oxidation.

Chronic clofibrate intake, on occasion, results in a muscular syndrome in man. We have investigated the effects of chronic clofibrate administration in rats on the electrical activity of a skeletal muscle (gastrocnemius), its composition, and its oxidation of palmitate and glucose. These effects have been compared with those in the liver. Clofibrate administration altered electromyographic pattern of gastrocnemius muscle (characteristic of myotonia), decreased its protein content, and impaired its oxidation of palmitate and glucose. These effects were quite different in the liver, because clofibrate intake increased the liver protein content and oxidation of palmitate without affecting the oxidation of glucose by this tissue. Whereas chronic clofibrate administration markedly increased the concentration of carnitine as well as the activity of mitochondrial carnitine palmitoyl-transferase in the liver, it decreased the activity of this enzyme in the gastrocnemius muscle without a significant effect on carnitine concentration in this tissue. Greater in vivo fatty acid oxidation by clofibratefed than by control rats was evidenced (a) by greater rate of production of (14)CO(2) in the expired air after injection of a tracer dose of [(14)C]palmitate and (b) by greater plasma and tissue concentrations of ketone bodies. We conclude that (a) paradoxical effects of clofibrate on fatty acid oxidation by the liver and skeletal muscle are related to changes in the activity of carnitine acyltransferase, (b) an increase in hepatic fatty acid oxidation may contribute to hypolipidemic effect of clofibrate, and (c) impairment of fatty acid and glucose oxidation by the muscle may be a factor in the development of muscular syndrome in patients receiving clofibrate treatment.

Animals↗
PubMed1979

Prevention of effects of ethanol on amino acid concentrations in plasma and tissues by hepatic lipotropic factors in rats.

The authors' previous studies have shown that hepatic steatosis of chronic ethanol ingestion in rats can be prevented by adding pyruvate, dihydroxyacetone, and riboflavin to their diet. In this study, the authors investigated the effect of chronic ethanol ingestion, with or without addition of the above metabolites to the diet, on protein and amino acid concentrations in tissues. Rats (120 g) were divided into three groups and fed isocalorically one of the fellowing diets for 30 days: control diet (28% fat, 15% protein, and 57% carbohydrate), ethanol diet (28% fat, 15% protein, 23% carbohydrate, and 24% ethanol), and metabolite diet (ethanol diet plus pyruvate, dihydroxyacetone, and riboflavin). Chronic ethanol ingestion reduced growth of muscle and intestinal mucosa without affecting that of liver and kidney. Among the 15 amino acids measured, chronic ethanol ingestion had the most consistent effect on plasma and tissue concentrations of leucine, alanine and alpha-amino-n-butyrate. The concentration of leucine was increased in muscle, liver, and plasma; that of alpha-amino-n-butyrate was increased in muscle and plasma, whereas that of alanine was decreased in plasma and liver. Addition of pyruvate, dihydroxyacetone, and riboflavin to the ethanol diet either totally or partially prevented ethanol-induced changes in plasma and tissue concentrations of amino acids despite similarity in plasma ethanol levels. Although these metabolites prevented the inhibition of the growth of intestinal mucosa, they were ineffective in blunting the effect of ehtanol on the skeletal muscle. This latter observation suggests that the mechanism of ethanol-induced inhibition of tissue growth is not the same for these tissues.

Amino Acids↗
PubMed1978

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

Amino Acids↗
PubMed1977

Clearance of dipeptides from plasma: role of kidney and intestine.

The metabolic fate of glycylglycine and glycyl-L-leucine administered intravenously to rats, and the processes involved in the clearance of these dipeptides from plasma, have been studied. The dipeptides disappeared rapidly from plasma without being lost in the urine or accumulating in body tissues, but concentrations of glycine or leucine, or both, increased markedly in plasma and body tissues. All tissues except blood had considerable hydrolase activity against Gly-Gly and Gly-Leu, with kidney and intestine being far more active than liver and muscle in this regard. When uptake of glycylsarcosine, which is resistant to hydrolysis, was investigated after intravenous injection, its disappearance from plasma was slower than that of Gly-Gly, but Gly-Sar accumulated in all tissues examined (liver, muscle, renal cortex and intestinal mucosa). Its concentration in the renal cortex far exceeded (over 14-fold) that in other tissues, and a considerable portion of the injected Gly-Sar dose appeared in the urine. Bilateral nephrectomy did not have a remarkable effect on the plasma half-life of Gly-Leu or Gly-Gly but markedly prolonged that of Gly-Sar. Nephrectomy also allowed greater tissue accumulation of Gly-Sar and recovery of Gly-Gly and Gly-Leu from tissues. The plasma half-life of Gly-Gly was also not remarkably affected by total enterectomy. These studies suggest that (a) clearance of dipeptides from plasma is chiefly a function of tissue uptake and hydrolysis, and (b) among dipeptides, those resistant to hydrolysis depend to a great extent on kidneys for their clearance from plasma.

Amino Acids↗
PubMed1977

Metabolism of intravenously administered dipeptides in rats: effects on amino acid pools, glucose concentration and insulin and glucagon secretion.

1. Studies were performed to investigate the metabolic fate of dipeptides when administered intravenously in rats. Glycyl-leucine, glycylglycine or glycylsarcosine was injected into the jugular vein. The plasma disappearance rate after the peak plasma concentrations was most rapid for glycyl-leucine and least rapid for glycylsarcosine. 2. During urine collection for 40 min, trace amounts of glycyl-leucine and glycylglycine and 13% of the injected glycylsarcosine were excreted. 3. Neither glycylglycine nor glycyl-leucine was detected in the liver, muscle, intestinal mucosa or renal cortex, but concentrations of glycine or leucine, or both, in these tissues were increased after each injection. In contrast, glycylsarcosine was recovered in all these tissues with concentrations in the renal cortex being far greater than in any other tissue, but sarcosine was found only in the renal cortex and intestinal mucosa. 4. The changes in plasma concentrations of free amino acids, glucose and glucagon, and tissue concentrations of free amino acids, were similar after the intravenous administration of glycyl-leucine and an equimolar mixture of free glycine and leucine. However, the amount of insulin secreted during the 40 min after glycyl-leucine injection was 1-6 times that produced after the injection of the corresponding amino acid mixture. 5. Results show that, within the present experimental conditions, the intravenous administration of dipeptides is as effective as that of the corresponding free amino acids in enriching the tissue pools of amino acids. It is suggested that efficient hydrolysis by cellular enzymes prohibits accumulation of intact dipeptides in body tissues.

Amino Acids↗