Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-terminal part sequences of pituitary growth hormone, N alpha-acetyl-hGH 7-13 and hGH 6-13, promoted conversion of glycogen synthase b to glycogen synthase a in skeletal muscle and adipose tissue when injected intravenously. The peptides also caused conversion of phosphorylase a to phosphorylase b in liver and adipose tissue, but not in muscle, where the peptides antagonised activation of phosphorylase. Synthase phosphatase activity in muscle and phosphorylase phosphatase activity in liver increased after injection of peptide, with time courses of change similar to those seen for muscle synthase and liver phosphorylase activities. Injection of peptide also decreased both the cyclic AMP dependent and independent synthase kinase activities in muscle. These results show that the insulin-like activities of these peptides on glycogen synthase and phosphorylase involve both increases in protein phosphatase activities and inhibition of protein kinase activities. These results are discussed in relation to the insulin-like activities of growth hormone.
Mol Cell Biochem 1987 Mar
PMID:Activation of phosphoprotein phosphatases by growth hormone sequences with insulin-like activity. 303 64

Insulin alone at concentrations of less than 1 to 5 uU/ml increased the enzyme activities of glycogen synthase, synthase phosphatase, phosphorylase, and phosphorylase phosphatase in hepatoma H4 cells in culture in the presence and absence of serum. Increase in total and active forms of glycogen synthase and phosphorylase were observed. Cycloheximide blocked the action of insulin on glycogen synthase, glycogen synthase phosphatase and phosphorylase phosphatase. The enzymes with the exception of glycogen synthase phosphatase were expressed with greater hormonal sensitivity in the absence as compared to the presence of serum in terms of hormone concentration required and or time of onset. These results demonstrate that these glycogen metabolizing enzymes are under long term control by insulin, with glycogen synthase being the most sensitive of the enzymes studied to the action of the hormone.
Mol Cell Biochem 1987 Jun
PMID:Long term regulation of glycogen metabolizing enzymes by insulin in H4 hepatoma cells. 304 Dec

Phosphorylase ab hybrid was demonstrated in perfused rat hearts and during the in vitro conversion of purified rat heart phosphorylase b. Phosphorylase ab hybrid was determined in rat heart extracts by the activating effect of AMP in the presence of caffeine. These results were confirmed by the quantitative determination of incorporated 32P in vitro and through the characteristic inhibition of ab hybrid by glucose-6-phosphate. As shown by our results, in aerobically perfused control hearts only the ab hybrid represents the active form of phosphorylase, its activity reaching about 20% of the total. In response to isoproterenol (5-1000 ng), the amount of ab hybrid rose to about 30-40%, preceding the rise of the a form, which increased in a dose-dependent manner up to 45% of the total. The great sensitivity of the ab form to AMP activation and glucose-6-phosphate inhibition supports its physiological significance in heart under in vivo conditions as well. Our results strongly suggest that the activity ratio -AMP/ + AMP reflects rather the percentage ratio of phosphorylated subunits than that of the activated (partially or totally phosphorylated) phosphorylase molecules.
Mol Cell Biochem 1986 Feb
PMID:Formation of partially phosphorylated phosphorylase in isoproterenol stimulated rat hearts. 308 38

The skin epithelium and its organelles use glycogen as well as glucose as source of energy. Therefore the characterisation of glycogen metabolism and the enzymes involved is important in the study of mechanisms regulating the normal or abnormal differentiation of skin organelles such as sebaceous glands and hair follicles. The present paper describes fluorimetric methods for the determination of glycogen and for the measurements of phosphorylase and phosphorylase kinase activity in one and the same lysate of minute tissue samples. The methods were tested for their suitability on freshly isolated human hair follicles and cultured hair follicle cells. The possible use of these techniques for studies on the pathophysiology of acne and hirsutism is discussed.
Mol Biol Rep 1987
PMID:Determination of glycogen and enzymes of glycogen metabolism in human hair follicles. 312 15

The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the other catalyzes the hydrolysis of adenosine, inosine, and guanosine but not MeSAdo. The substrate specificity of trypanosomal MeSAdo/Ado phosphorylase differed from that of a mammalian MeSAdo phosphorylase (derived from murine Sarcoma 180 cells) in that it was able to phosphorolyze 2'-deoxyadenosine, 3'-deoxyadenosine and 2',3'-dideoxyadenosine. In addition, the trypanosomal phosphorylase was able to utilize the nucleoside analog, 6-methylpurine 2'-deoxyribonucleoside, as an alternative substrate, whereas the mammalian enzyme could not. Because of these differences, cytotoxic analogs of MeSAdo may be designed that are selectively activated by the trypanosomal MeSAdo/Ado phosphorylase.
Mol Biochem Parasitol 1988 Jan 15
PMID:Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells. 312 30

The slime mold Dictyostelium discoideum has two forms of the enzyme glycogen phosphorylase. The inactive phosphorylase 'b' form requires 5' AMP for activity and is present in early development. The active phosphorylase 'a' form is 5' AMP independent and occurs during later development. We here show that the 92 kd 'b' enzyme subunit exists either as a singlet or a doublet upon SDS-PAGE, depending on the method of sample extraction. In the presence of exogenously added Mn2+ and ATP, the phosphorylase 'b' shows apparent conversion into a 5' AMP independent form as measured by enzyme activity. In addition, Mn2+ and ATP also support an in vitro phosphorylation of the 92 kd phosphorylase 'b' subunit. We also demonstrate phosphorylation of the 'b' enzyme subunit in vivo by 32-P incorporation into the enzyme protein. A protein kinase responsible for the observed in vitro phosphorylation of the phosphorylase 'b' subunit is characterized.
Mol Cell Biochem 1988 Sep
PMID:Glycogen phosphorylase 'b' in Dictyostelium: stability and endogenous phosphorylation. 314 89

Giardia lamblia is totally dependent on salvage synthesis for its pyrimidine requirements. The salvage pathway enzyme, uridine phosphorylase (pyrimidine nucleoside phosphorylase) was purified to apparent homogeneity from G. lamblia crude extracts by fast protein liquid chromatography and gel filtration on a Superose 12 column, resulting in an overall 3500 fold purification and a recovery of 7.5%. Mono P chromatofocusing gave rise to a major activity peak eluting from the column at pH 5.9, indicating that the enzyme has an isoelectric point (pI) at approximately this value. The molecular weight was found to be 43,000 +/- 2000 from the Superose 12 column, while sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the purified enzyme gave a single protein band with a subunit molecular weight of 38,000 +/- 2000, indicating that it is a monomer. The activities of uridine, deoxyuridine and thymidine phosphorylases from G. lamblia remained associated throughout the purification procedure, suggesting that one enzyme is responsible for the three enzyme activities. The ratio of activities was consistent throughout the purification procedure. In the reverse (anabolic) direction, the enzyme could use both uracil and thymine as substrates. The properties of the phosphorylase differ significantly from those of the mammalian host.
Mol Biochem Parasitol 1988 Sep
PMID:Purification and characterization of uridine (thymidine) phosphorylase from Giardia lamblia. 318 13

Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.
Mol Pharmacol 1988 Feb
PMID:Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle. 334 81

Cellular and biochemical analyses of the toxic effects of the thymidine analog, 5-hydroxymethyl-2'-deoxyuridine (hmdUrd), were carried out using V79.5 Chinese hamster cells. It was found that the toxic effects of hmdUrd could be totally suppressed by the addition of thymidine at 1/10th the concentration of hmdUrd. When other pyrimidines were tested, deoxyuridine was found to also suppress toxicity, although not as well as thymidine, while orotate, uridine, cytidine, and deoxycytidine did not have significant effect. Biochemical analyses of the metabolic fate of hmdUrd demonstrated low but significant levels of hmdUrd triphosphate and the incorporation of 5-hydroxymethyluracil (hmUra) residues into DNA. Surprisingly, in addition to these metabolites, relatively high levels of free hmUra were also detected in the acid-soluble cell extracts. Further analysis demonstrated that when V79.5 cells were exposed to hmdUrd significant amounts of hmUra were released into the culture medium. In vitro assays provided evidence that hmdUrd was first phosphorylated to its monophosphate and then degraded to hmUra, possibly via the action of a new enzyme, hydroxymethyldeoxyuridylate phosphorylase. Exposure of cells to hmUra alone, at concentrations as high as 3 mM, had no effect on viability. However, when V79.5 cells were simultaneously exposed to low, nontoxic concentrations of hmdUrd and high, nontoxic concentrations of hmUra, a synergistic reduction in viability was observed. This synergistic effect was found to correlate with increased incorporation of hmUra into DNA, possibly via end-product inhibition of an hmUra-DNA glycosylase.
Somat Cell Mol Genet 1986 Sep
PMID:Biochemical analysis of toxic effects of 5-hydroxymethyl-2'-deoxyuridine in mammalian cells. 346 3

Ablation of premigratory trunk neural crest over somites 10 through 20 gives rise to chick hearts which lack sympathetic innervation. Norepinephrine, the neurotransmitter of the postganglionic sympathetic nerves, increases the rate of formation of cyclic AMP (cAMP) in cells. Cyclic AMP the modulator of certain key enzymes of metabolism, was decreased in sympathetically-aneural hearts. Six histochemical assays were used to investigate the metabolic profile of sympathetically aneural hearts as compared to control hearts. NADH-tetrazolium reductase activity (indicator of oxidative metabolism), glyceraldehyde 3-phosphate dehydrogenase activity (indicator of glycolytic rate), beta-hydroxybutyrate dehydrogenase (indicator of beta-oxidation of fatty acids), and oil red 0 assay (neutral lipid content) each demonstrated no difference between aneural and control hearts. Periodic acid-Schiff method for glycogen content, indicated greater stores of glycogen in aneural hearts compared to controls. alpha-Glucan phosphorylase, an enzyme responsible for glycogen hydrolysis, showed less activity in aneural hearts than in controls. The results indicate that the sympathetically aneural heart's metabolism is altered by decreased capability in the maximal rate of glycogen breakdown (decreased phosphorylase Vmax) and subsequent increased storage of the glycogen substrate. Enzymes of other energy transformation pathways were unaltered in the absence of sympathetic nerves.
J Mol Cell Cardiol 1987 Apr
PMID:Carbohydrate, lipid and oxidative metabolism in the sympathetically aneural chick heart. 361 18


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