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

After glucagon injection, rats showed virtually identical percentage increases in hepatic histidine-pyruvate aminotransferase and serine-pyruvate aminotransferase activities, both in the mitochondria and in the cytosol. Histidine-pyruvate aminotransferase isoenzyme 1, with pI8.0, was purified to homogeneity from the mitochondrial fraction of liver from glucagon-injected rats. The purified enzyme catalysed transamination between a number of amino acids and pyruvate or phenylpyruvate. For transamination with pyruvate, the activity with serine reached a constant ratio to that with histidine during purification, which was unchanged by a variety of treatments of the purified enzyme. Serine was found to act as a competitive inhibitor of histidine transamination, and histidine of serine transamination. These results suggest that histidine-pyruvate amino-transferase isoenzymes 1 is identical with serine-pyruvate aminotransferase. The enzyme is probably composed of two identical subunits with mol. wt. approx. 38000. The absorbance maximum at 410 nm and the inhibition by carbonyl reagents strongly indicate the presence of pyridoxal phosphate.
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PMID:Identity of isoenzyme 1 of histidine-pyruvate aminotransferase with serine-pyruvate aminotransferase. 1 42

Serine dehydratase (L-serine hydro-lyase, EC 4.2.1.13) WAS DEMONSTRATED IN LIVER TISSUE OF RATS BY AN INdirect immunofluorescent method. In the adult rat liver, serine dehydratase was localized to periportal hepatocytes, diffusely in their cytoplasm. The enzyme-specific fluorescence was absent or extremely low in the centrolobular hepatocytes. It was not demonstrated in nonparenchymal cells. Feeding a 90% protein diet for 5 days caused marked induction of this enzyme in the periportal and midzonal hepatocytes but no induction in the centrolobular hepatocytes. In the newborn rat liver, there was no apparent intralobular heterogeneity seen in the distribution of serine dehydratase, either before or after dietary induction. After 1 week of age, there was a gradual development of the intralobular hetero-geneity of the enzyme, which was emphasized by dietary stimulation. A comparative study of the induction pattern between the livers of intact and adrenalectomized rats suggested that there is no heterogeneity among serine-dehydratase-positive cells with respect to hormonal regulation of this enzyme by either glucagon or cortisone.
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PMID:Immunohistochemical demonstration of serine dehydratase in rat liver. 16 93

Serine dehydratase was induced in the kidneys of normal rats by the administration of either glucagon or dexamethasone. The increase in enzyme activity was associated with an increase in both enzyme protein and its mRNA, which were determined respectively by Western blot and RNA blot analysis. No apparent differences were observed between kidney and liver in the molecular weights of serine dehydratase proteins and the sizes of their mRNAs. Although kidney serine dehydratase was dramatically induced by either glucagon or dexamethasone, the liver enzyme was induced by glucagon but not by dexamethasone alone in the intact rat. On the other hand, liver serine dehydratase was induced in starvation, diabetes mellitus, and a high-protein diet. The kidney enzyme could not be induced under any of these conditions.
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PMID:Regulation of the expression of the serine dehydratase gene in the kidney and liver of the rat. 238 71

Membrane-permeant cAMP derivatives (dibutyryl- and 8-bromo-cAMP) increase gap-junctional conductance within minutes when applied to voltage-clamped pairs of rat hepatocytes. Glucagon also increases junctional conductances, but the response has a more rapid onset and is more rapidly reversible. The glucagon effect can be prevented by intracellular injection of the protein inhibitor of the cAMP-dependent protein kinase (Walsh inhibitor), indicating that the catalytic subunit of cAMP-dependent protein kinase is directly involved. The 27-kDa major gap junction polypeptide is phosphorylated when liver cells dissociated into small groups are incubated with 32P. Addition of 8-bromo-cAMP to cells increases the incorporation of 32P into the 27-kDa junctional protein. Serine is the amino acid residue that is phosphorylated. When isolated liver gap junctions are incubated in the presence of catalytic subunit of the cAMP-dependent protein kinase, the 27-kDa gap junction polypeptide is phosphorylated with low stoichiometry on serine. The rapid increases in gap junctional conductance caused by agents that elevate cAMP and phosphorylation of the gap junction protein by cAMP-dependent protein kinase suggest that cAMP-dependent phosphorylation of the gap junction channel modulates the conductance of liver gap junctions.
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PMID:cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide. 301 Mar 11

1. The activities of l-serine dehydratase and l-serine-pyruvate aminotransferase were determined in rat liver during foetal and neonatal development. 2. l-Serine-pyruvate aminotransferase activity begins to develop in late-foetal liver, increases rapidly at birth to a peak during suckling and then decreases at weaning to the adult value. 3. l-Serine dehydratase activity is very low prenatally, but increases rapidly after birth to a transient peak. After a second transient peak around the time weaning begins, activity gradually rises to the adult value. Both of these peaks have similar isoenzyme compositions. 4. In foetal liver both l-serine dehydratase and l-serine-pyruvate aminotransferase activities are increased after injection in utero of glucagon or dibutyryl cyclic AMP. Cycloheximide or actinomycin D inhibited the prenatal induction of both enzymes and actinomycin D blocked the natural increase of l-serine dehydratase immediately after birth. Glucose or insulin administration also blocked the perinatal increase of l-serine dehydratase. 5. After the first perinatal peak of l-serine dehydratase, activity is increased by cortisol and this is inhibited by actinomycin D. After the second postnatal peak, activity is increased by amino acids or cortisol and this is insensitive to actinomycin D inhibition. Glucose administration blocks the cortisol-stimulated increase in l-serine dehydratase and also partially lowers the second postnatal peak of activity. 6. The developmental patterns of the enzymes are discussed in relation to the pathways of gluconeogenesis from l-serine. The regulation of enzyme activity by hormonal and dietary factors is discussed with reference to the changes in stimuli that occur during neonatal development and to their possible mechanisms of action.
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PMID:Regulation of hepatic L-serine dehydratase and L-serine-pyruvate aminotransferase in the developing neonatal rat. 437 55

Serine dehydratase activity is absent from the rat foetal liver and normally appears in the immediate postnatal period. In foetal hepatocytes cultured from livers of various gestational ages, enzyme activity can be induced only in the simultaneous presence of dexamethasone and dibutyryl cyclic AMP in the culture medium. Adrenalin and glucagon can replace dibutyryl cyclic AMP. Actinomycin D and cordycepin both repress the response, a result that suggests the induction of enzyme synthesis involves the initial transcription of the enzyme gene(s). Inducibility is assessed in cultures prepared from foetuses aged between 15 and 19 days of gestation after 48 h of culture. No induction is obtained in cells from 15 day foetuses, only a marginal induction from 16 day foetuses, and a substantial induction from older foetuses. In cultures from older foetuses, 6-18 fold inductions are already demonstrable after 24 h of culture. While hepatocytes from more mature foetuses are able to acquire inductibility during culture, cells taken from 15 day foetuses do not develop in the same manner in spite of being maintained under identical conditions. These results suggest that a differentiation event occurs in vivo at about day 16 of foetal development which renders the hepatocyte inducible when cultured. Cells taken prior to this stage do not appear to acquire inducibility. This system represents a case of enzymic differentiation and requires the simultaneous presence of two inducer molecules. The mechanism of induction may represent a unique system in cellular differentiation.
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PMID:Enzymic differentiation in cultured foetal hepatocytes of the rat. Induction of serine dehydratase activity by dexamethasone and dibutyryl cyclic AMP. 631 60

Processing and uptake of the precursor of serine: pyruvate aminotransferase [EC 2.6.1.51] by mitochondria were studied in vitro and in vivo. Serine: pyruvate aminotransferase was synthesized mainly on free ribosomes as judged by immunoprecipitation of puromycin-labeled nascent peptides prepared from free and bound ribosomes. The precursor of rat liver serine:pyruvate aminotransferase (pSPT) synthesized in vitro was post-translationally processed to an apparently mature form by isolated rat liver mitochondria. Available evidence indicated that the processed product was localized in the matrix of mitochondria. Mature serine:pyruvate aminotransferase did not inhibit the in vitro processing, suggesting that the extra peptide was necessary for the mitochondrial uptake of the precursor. In the livers of rats fed a vitamin B6-deficient high-protein diet, the induction by glucagon of serine:pyruvate aminotransferase occurred and most of the induced enzyme existed in mitochondria as the apo-form, suggesting that pSPT was taken up by mitochondria and processed in the apo-form under the conditions employed. In the in vitro system, on the other hand, the processing of pSPT proceeded both in the absence and presence of pyridoxal 5'-phosphate. Should the precursor also bind the prosthetic molecule, therefore, it would be transported into mitochondria in both the apo- and holo-forms. When isolated rat hepatocytes were labeled with [35S]methionine, labeled pSPT appeared in the cytosolic fraction and was transported rapidly into mitochondria in association with the processing. This uptake and processing were inhibited by a fluorescent laser dye, rhodamine 123, and the precursor accumulated in the cytosol in the presence of the dye.
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PMID:Uptake and processing of serine: pyruvate aminotransferase precursor by rat liver mitochondria in vitro and in vivo. 672 36

Disturbances of carbohydrate metabolism during acute uraemia are characterized by the degradation of liver and muscle glycogen with a simultaneous activation of hepatic gluconeogenesis. After binephrectomy, the substitution of essential amino acids and keto analogues stimulate liver, but not skeletal muscle glycogen synthesis. Serine proves to be an optimal substrate for liver gluconeogenesis and muscle glycogen generation under acute uraemic conditions. Propranolol does not influence glycogenolysis of skeletal muscle in acutely uraemic rats. During starvation, acute uraemia leads to an increase of total carbohydrate content as well as of glycogen and glucose concentrations in heart muscle Alterations in carbohydrate contents are not observed in the kidney after ureter ligation. Enhanced glycogenolysis of skeletal muscle and liver during acute uraemia may be due to activation of phosphorylase kinase caused by the increased serum concentrations of various hormones (glucagon, catecholamines, parathormone) as well as free proteolytic activity, an increase of intracellular Ca2+-concentration and finally by alterations in the structure of contractile proteins.
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PMID:Carbohydrate metabolism and uraemia-mechanisms for glycogenolysis and gluconeogenesis. 745 93

Extensive structure activity analysis has allowed us to identify specific residues in the glucagon sequence that are responsible for either receptor recognition or signal transduction. For instance, we have demonstrated that aspartic acid 9 and histidine 1 are essential for activation, and that an ionic interaction between the negative carboxylate and the protonated imidazole may contribute to the activation reaction at the molecular level. In the absence of the carboxylic group at position 9, aspartic 21 or aspartic 15 might furnish distal electrostatic effects to maintain partial agonism. Further investigation established that each of the 4 serine residues in the hormone play distinct roles. Serine 8 provides an important determinant of binding. Whereas neither serines 2, 11, nor 16 are required for receptor recognition. We have shown that serine 16 is essential for signal transduction and thus have identified it to be the third residue in glucagon to participate in a putative catalytic triad together with aspartic 9 and histidine 1, in the transduction of the glucagon response. In this work, we utilized insights into the functional significance of particular residues in the peptide appropriated from our structure-function assignments, as the basis of a molecular approach for the design of active-site directed antagonists of glucagon. The importance as well as the accuracy of our findings are confirmed by the synthesis of a series of improved glucagon antagonists based on replacements at positions 1, 9, 11, 16, and 21. The inhibition index, (I/A)50, of our best antagonist des-His1-[Nle9-Ala11-Ala16]glucagon amide, has been improved 10-fold over the previous best glucagon inhibitor.
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PMID:Multiple-site replacement analogs of glucagon. A molecular basis for antagonist design. 817 63


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