Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme.
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PMID:Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. 0 99

The effectiveness of dietary and hormonal treatments in inducing several pyridoxal phosphate-(PLP)-dependent enzymes has been examined in vitamin B-6 deficient rats. Holo- and apoenzymes of serine dehydratase and ornithine aminotransferase were inducible in both control and deficient rats by feeding them 80% casein diets or by injecting them with glucagon. Holo- and apotyrosine aminotransferase were induced in both control and deficient rats by injecting them with glucagon or with dexamethasone phosphate. Phosphoenolpyruvate carboxykinase, a non-PLP-dependent enzyme, was inducible in both control and deficient rats by glucagon treatment if the rats were fed, but not if they had been starved. The degree of induction of certain enzymes depended upon whether rats were fed ad libitum, starved overnight, or fed a protein-free diet prior to the induction period. Phosphoenolpyruvate carboxykinase activities were about the same in both control and deficient rats. In vitamin B-6 deficient rats, both uninduced and induced activities of serine dehydratase, ornithine aminotransferase, and tyrosine aminotransferase assayed in the prsence of PLP, but not in its absence, either equaled or exceeded control values under most experimental conditions. Synthesis of excess of apoenzyme of PLP-dependent enzymes generally accounted for the high total enzyme activity in deficient rats. Differences between values for control and deficient rats could not be accounted for by differences in liver cyclic AMP concentrations nor were they apparently related to reduced food intake of the deficient rats. High apoenzyme concentration during depletion of coenzyme would tend to prevent depletion of active enzyme.
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PMID:Induction of pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. 1 69

DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp.
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PMID:Stimulation of tyrosine aminotransferase activity by dl-alpha-methyltryptophan. 23 76

Hepatic ornithine aminotransferase (EC 2.6.1.13) (OAT) is a mitochondrial matrix enzyme that plays a role in amino acid catabolism and in gluconeogenesis. In rats, the synthesis of hepatic OAT is regulated by glucagon, dietary protein, and glucose. Serum-free primary cultures of adult rat hepatocytes were used to demonstrate that glucagon, cyclic AMP, and glucose are able to alter OAT synthesis by a direct action on hepatocytes. The rates of OAT synthesis were measured by immunoprecipitation of pulse-labeled OAT with an affinity-purified monospecific antibody. Ten hours after cyclic AMP addition to the culture medium, the relative rate of OAT synthesis reached a peak value that was six- to eightfold above the control rate. OAT activity accumulated more slowly, reaching a level that was approximately threefold above the control by 24 h. The inclusion of glucose in the culture medium inhibited the increases in OAT synthesis and activity in a dose-dependent manner. Although synthesized as a precursor (pOAT), no pOAT was detected under control, induced, or carbohydrate-inhibited conditions; this suggests that pOAT processing may not be a regulatory site of OAT expression. By following the loss of labeled OAT, a half-life of 34 h in these cultures under all of the above conditions was observed. Regulation of OAT levels in cultured hepatocytes appears to be achieved primarily through changes in the rate of OAT synthesis.
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PMID:Regulation of ornithine aminotransferase by cyclic AMP and glucose in primary cultures of adult rat hepatocytes. 298 11

The mitochondrial matrix enzyme, ornithine aminotransferase, is induced in rat liver by the administration of a diet high in protein and by glucagon. The rate of synthesis of the enzyme is increased 100-fold in the livers of rats maintained on a 60% relative to a 0% protein diet, whereas the levels of functional and hybridizable mRNA measured by in vitro translation and through the use of a cloned cDNA probe increased by only 2- to 6-fold and 2- to 3-fold, respectively. Under conditions of glucagon induction that resulted in a 10- to 12-fold increase in the rate of enzyme synthesis, the relative level of functional ornithine aminotransferase mRNA increased by only 2-fold, and the level of hybridizable mRNA actually decreased. The rate of polypeptide chain elongation and the relative number of ornithine aminotransferase nascent chains on polysomes were 2-fold and 23-fold greater, respectively, in hepatocytes derived from 60% relative to 0% protein-fed rats. Using these data, a 23-fold increase in the translational efficiency of the mRNA was calculated. This increase, along with a 2-fold increase in the mRNA level, completely account for the 40-fold increase in the rate of ornithine aminotransferase synthesis observed in hepatocytes derived from 60% protein-fed rats. We conclude that ornithine aminotransferase synthesis is regulated at both a translational and a pretranslational level in rat liver.
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PMID:Translational and pretranslational control of ornithine aminotransferase synthesis in rat liver. 613 59

The studies described in this paper demonstrate rather conclusively the efficacy of the study of the regulation of gene expression in primary cultures of adult rat hepatocytes. The utilization of these cells in completely defined medium allows one to determine the exact environmental conditions for the regulation of the expression of specific genes. In the studies described in this work, we have demonstrated that the regulation of glucokinase involved three hormones, insulin, corticosteroids, and T3. In contrast, the regulation of an enzyme involved primarily in fatty acid metabolism, ATP-citrate lyase, required only insulin and T3 for its full expression. Cyclic GMP appeared to be involved in the regulation of glucokinase, but not ATP-citrate lyase, a fact that would be extremely difficult to demonstrate clearly in vivo. The regulation of the gluconeogenic enzyme, ornithine aminotransferase, in vitro involved only a single hormone, glucagon, the inhibition of induction by corticoid steroids demonstrable in vivo being absent in cell culture. However, the repressive effect of glucose on the induction of this enzyme was quite comparable to that seen in vivo and was not mediated through cyclic AMP or insulin, based on findings in cell culture. Thus, the requirements for and the mechanisms involved in enzyme induction and repression by hormones and glucose may be much more easily studied in primary cultures of rat hepatocytes than in vivo, or even in hepatoma cell lines, where relatively few genes are expressed as compared with adult liver. In addition to the regulation of enzyme levels, the characteristics of protein secretion may be investigated in primary cultures of rat hepatocytes and compared with the biochemical and physiological parameters in the whole organism. This was exemplified by the study of the synthesis and secretion of alpha 2u-globulin that was secreted into the culture medium in both glycosylated and nonglycosylated forms but was maintained in the circulation in vivo, principally as the glycosylated form. Furthermore, the function of glycosylation in this particular instance may be deduced from a combination of the in vivo and in vitro approaches. The advantages of the use of primary hepatocyte cultures for the study of the regulation of gene expression in mammalian tissue has only recently been explored. Future investigations of the regulation of a variety of enzymes in these cultures as well as a study of the regulation of the synthesis of their messenger RNA are now possible and should provide an exciting system in which to understand at a molecular level the regulation of the expression of a number of genes.
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PMID:Regulation of gene expression in primary cultures of adult rat hepatocytes on collagen gels. 616 26

The rates of oxidation of arginine and ornithine that occurred through a reaction pathway involving the enzyme ornithine aminotransferase (EC 2.6.1.13) were determined using (14)C-labeled amino acids in the isolated nonrecirculating perfused rat liver. At physiological concentrations of these amino acids, their catabolism is subject to chronic regulation by the level of protein consumed in the diet. (14)CO(2) production from [U-(14)C]ornithine (0.1 mM) and from [U-(14)C]arginine (0.2 mM) was increased about fourfold in livers from rats fed 60% casein diets for 3-4 days. The catabolism of arginine in the perfused rat liver, but not that of ornithine, is subject to acute regulation by glucagon (10(-7) M), which stimulated arginine catabolism by approximately 40%. Dibutyryl cAMP (0.1 mM) activated arginine catabolism to a similar extent. In retrograde perfusions, glucagon caused a twofold increase in the rate of arginine catabolism, suggesting an effect of glucagon on arginase in the perivenous cells.
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PMID:Catabolism of arginine and ornithine in the perfused rat liver: effect of dietary protein and of glucagon. 1071 May 7

The mechanism of pellagrous changes in skin caused by a deficiency of vitamin B6 was studied in respect to neogenesis of proline in skin collagen and glucose metabolism. In vitamin B6 deficiency the insulin/glucagon coefficient in serum decreased significantly from 3.02 to 2.32, indicating a metabolic change towards gluconeogenesis. A deficiency of vitamin B6 caused a decrease in the levels of vitamin B6-dependent enzymes, such as ornithine aminotransferase, alanine aminotransferase, and aspartate aminotransferase, which also contribute to gluconeogenesis. Because the conversion of ornithine to proline via pyrroline-5-carboxylate was suppressed due to the decrease in ornithine aminotransferase activity, the amount of proline in the skin collagen fraction also decreased significantly in vitamin B6-deficient rats compared with the pair-fed control. These results suggest that the pellagrous lesions in vitamin B6-deficiency are caused by an impaired synthesis of proline from ornithine, which results in the suppression of collagen neogenesis in the skin.
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PMID:Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. 1617 47