phosphorylase a


Summary: The active form of GLYCOGEN PHOSPHORYLASE that is derived from the phosphorylation of PHOSPHORYLASE B. Phosphorylase a is deactivated via hydrolysis of phosphoserine by PHOSPHORYLASE PHOSPHATASE to form PHOSPHORYLASE B.

Top Publications

  1. Al Habori M, Raman A, Lawrence M, Skett P. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. Int J Exp Diabetes Res. 2001;2:91-9 pubmed
    ..Fenugreek extracts had no effect on basal levels of glycogen phosphorylase a (HGPa) activity in rat hepatocyte suspensions...
  2. Ren J, Gulve E, Cartee G, Holloszy J. Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle. Am J Physiol. 1992;263:E1086-91 pubmed
    ..Despite reversal of the increase in percentage of phosphorylase a after a few minutes, continued glycogen breakdown can occur during strenuous exercise...
  3. Schliselfeld L, Danon M. Inverse relationship of skeletal muscle glycogen from wild-type and genetically modified mice to their phosphorylase a activity. Biochem Biophys Res Commun. 2002;290:874-7 pubmed
    ..per g muscle), and 52% or more of its glycogen phosphorylase activity without AMP (69% +/- 17% glycogen phosphorylase a)...
  4. Goldsmith E, Sprang S, Hamlin R, Xuong N, Fletterick R. Domain separation in the activation of glycogen phosphorylase a. Science. 1989;245:528-32 pubmed
    The crystal structure of glycogen phosphorylase a complexed with its substrates, orthophosphate and maltopentaose, has been determined and refined at a resolution of 2.8 angstroms...
  5. Armstrong C, Doherty M, Cohen P. Identification of the separate domains in the hepatic glycogen-targeting subunit of protein phosphatase 1 that interact with phosphorylase a, glycogen and protein phosphatase 1. Biochem J. 1998;336 ( Pt 3):699-704 pubmed
    ..1 (PP1) have identified three separate domains that are responsible for binding of PP1, glycogen and phosphorylase a. The glycogen-binding domain spans the centre of GL between residues 144 and 231 and appears to be distinct ..
  6. Meinke M, Edstrom R. Muscle glycogenolysis. Regulation of the cyclic interconversion of phosphorylase a and phosphorylase b. J Biol Chem. 1991;266:2259-66 pubmed
    ..Energy effectiveness is shown to be a possible evolutionary factor in favor of the development of zero-order ultrasensitivity in compartmentalized systems. ..
  7. Ercan N, Gannon M, Nuttall F. Allosteric regulation of liver phosphorylase a: revisited under approximated physiological conditions. Arch Biochem Biophys. 1996;328:255-64 pubmed
    ..It is present in two interconvertible forms, phosphorylase a and b. The a form is the active form and is rate limiting in glycogen degradation...
  8. Weng Y, Shukla S. Effects of chronic ethanol treatment on the angiotensin II-mediated p42/p44 mitogen-activated protein kinase and phosphorylase a activation in rat hepatocytes. Alcohol. 2003;29:83-90 pubmed
    ..In hepatocytes obtained from rats fed ethanol for 6 weeks, ANG II-stimulated phosphorylase a was reduced, and this activity was calcium dependent and p42/p44 MAPK independent...
  9. Mvumbi L, Stalmans W. High-affinity binding of glycogen-synthase phosphatase to glycogen particles in the liver. Role of glycogen in the inhibition of synthase phosphatase by phosphorylase a. Biochem J. 1987;246:367-74 pubmed
    ..25 mg/ml, and virtually complete at 1 mg/ml. These findings explain long-standing observations that in fasted animals the liver contains appreciable amounts of both synthase and phosphorylase in the active form. ..

More Information


  1. Ercan Fang N, Nuttall F. The effect of caffeine and caffeine analogs on rat liver phosphorylase a activity. J Pharmacol Exp Ther. 1997;280:1312-8 pubmed
    Liver phosphorylase a is stimulated by adenosine monophosphate. It is inhibited by adenosine diphosphate, adenosine triphosphate and glucose...
  2. Lawrence J, Smith R. Phosphorylase kinase isozymes and phosphorylase in denervated skeletal muscles. Muscle Nerve. 1990;13:133-7 pubmed
    ..The decreases in these enzymes explain, at least in part, the marked alterations in glycogen metabolism that occur after motor denervation. ..
  3. Gurnack M, Edstrom R. Binary affinity chromatography for the purification of glycogen phosphorylase. Protein Expr Purif. 1990;1:142-6 pubmed
    ..The glycogen-impregnated beads were able to bind 9 mg/ml of phosphorylase a or b...
  4. Albano E, Carini R, Parola M, Bellomo G, Goria Gatti L, Poli G, et al. Effects of carbon tetrachloride on calcium homeostasis. A critical reconsideration. Biochem Pharmacol. 1989;38:2719-25 pubmed
  5. Schmidt H, Wegener G. Glycogen phosphorylase in fish muscle: demonstration of three interconvertible forms. Am J Physiol. 1990;258:C344-51 pubmed
    ..Results suggest that three interconvertible forms of phosphorylase exist simultaneously in crucian muscle and that hybrid phosphorylase is active in contracting muscle in vivo. ..
  6. Neumann J, Maas R, Boknik P, Jones L, Zimmermann N, Scholz H. Pharmacological characterization of protein phosphatase activities in preparations from failing human hearts. J Pharmacol Exp Ther. 1999;289:188-93 pubmed
    ..In the past, cardiac serine/threonine phosphatases have been studied using phosphorylase a as substrate...
  7. Fedorov S, Uyeda K. Oscillation in fructose 2,6-bisphosphate levels and in the phosphorylation states of fructose 6-phosphate,2-kinase:fructose-2,6-bisphosphatase in ischemic rat liver. J Biol Chem. 1992;267:20826-30 pubmed
  8. Yamanouchi K, Stephens T, Chikada K, Dominianni S, Behforouz H, Scislowski P, et al. Metabolic effects of proglycosyn. Arch Biochem Biophys. 1992;294:609-15 pubmed
    ..phosphoprotein phosphatase activity in postmitochondrial extracts, as measured by dephosphorylation of phosphorylase a and glycogen synthase D, but this action required a very high concentration of the compound, making it ..
  9. Chan C, McNall S, Krebs E, Fischer E. Stimulation of protein phosphatase activity by insulin and growth factors in 3T3 cells. Proc Natl Acad Sci U S A. 1988;85:6257-61 pubmed
    ..resulted in a rapid and transient activation of protein phosphatase activity as measured by using [32P]phosphorylase a as substrate...
  10. Barron J, Kopp S. Fatty acid alters glycogen metabolism in contracting vascular smooth muscle. Biochim Biophys Acta. 1989;1012:69-73 pubmed
    ..001). Stimulation of glycogen phosphorylase a activity with contraction was also enhanced with palmitate...
  11. Diaz Guerra M, Bosca L. Lack of translocation of protein kinase C from the cytosol to the membranes in vasopressin-stimulated hepatocytes. Biochem J. 1990;269:163-8 pubmed reflected by the changes in the concentrations of inositol trisphosphate and Ca2+, and in glycogen phosphorylase a activity...
  12. Cuenda A, Centeno F, Gutierrez Merino C. Modulation by phosphorylation of glycogen phosphorylase-sarcoplasmic reticulum interaction. FEBS Lett. 1991;283:273-6 pubmed
  13. Honkanen R, Dukelow M, Zwiller J, Moore R, Khatra B, Boynton A. Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases. Mol Pharmacol. 1991;40:577-83 pubmed
    ..Thus, due to the high specificity of nodularin for PP2A and PP1, this hepatotoxin may prove to be useful as a probe for distinguishing the activity of these protein phosphatases in cell extracts. ..
  14. Knight W, Sem D, Smith K, Miziorko H, Rendina A, Cleland W. Phosphorylated thiosugars: synthesis, properties, and reactivity in enzymatic reactions. Biochemistry. 1991;30:4970-7 pubmed
    ..6. The free energy of hydrolysis of the phosphorylated thiol is thus -7.2 kcal/mol at pH 7.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  15. Giurgea R, Puica C, Coprean D. Biochemical modifications induced by Timorom in the liver carbohydrate metabolism of male and female rats. Rev Roum Physiol (1990). 1990;27:209-13 pubmed
    ..Many of the biochemical modifications, obtained after the Timorom treatment, disappeared at the end of the first post-treatment month. ..
  16. Kloeker S, Reed R, McConnell J, Chang D, Tran K, Westphal R, et al. Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein. Protein Expr Purif. 2003;31:19-33 pubmed
    ..Together, these findings increase our understanding of the biochemistry of alpha4/phosphatase complexes and suggest that the alpha4 binding site within PP2A may include the phosphatase catalytic domain. ..
  17. Sakaguchi S, Ibata H, Yokota K. Participation of calcium ion on depletion mechanism of liver glycogen by purified glucocorticoid antagonizing factor released in blood during endotoxemia. Microbiol Immunol. 1990;34:985-94 pubmed
    ..The phosphorylase a activity in liver 2 hr after injection of GAF plus cortisone did not show a significant difference as ..
  18. Quintana I, Grau M, Moreno F, Soler C, Ramirez I, Soley M. The early stimulation of glycolysis by epidermal growth factor in isolated rat hepatocytes is secondary to the glycogenolytic effect. Biochem J. 1995;308 ( Pt 3):889-94 pubmed
    ..Both glucagon and adrenaline increased phosphorylase a activity by more than 130%; EGF increased this activity by about 30%...
  19. Leijendekker W, Edauw P, van Hardeveld C, Simonides W. Phosphorylase a formation in protein-glycogen particles isolated from fast-twitch muscle of euthyroid and hypothyroid rats. Arch Biochem Biophys. 1989;274:120-9 pubmed
    ..Hypothyroidism reduced the rate of phosphorylase a formation by 50-70% in the P2 suspension. Glucose 6-phosphate (0.4-1...
  20. Chesley A, Hultman E, Spriet L. Effects of epinephrine infusion on muscle glycogenolysis during intense aerobic exercise. Am J Physiol. 1995;268:E127-34 pubmed
    ..5 +/- 25.3 vs. Epi 240.6 +/- 12.1 mmol/kg dry muscle). In addition, the degradation of muscle ATP and phosphocreatine and the accumulation of muscle lactate, ADP, and AMP were similar between trials.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  21. Marino A, Bartolome B, Trueba M, Sancho M, Macarulla J. Increased phospholipid methylation and glycogen phosphorylase activation after a single dose of dexamethasone in mouse liver. Exp Clin Endocrinol. 1988;92:314-22 pubmed
    Two different effects on phospholipid methylation and glycogen phosphorylase a activation were accomplished by treating mice livers with dexamethasone...
  22. Barford D, Hu S, Johnson L. Structural mechanism for glycogen phosphorylase control by phosphorylation and AMP. J Mol Biol. 1991;218:233-60 pubmed
    The crystal structures of activated R state glycogen phosphorylase a (GPa) and R and T state glycogen phosphorylase b (GPb) complexed with AMP have been solved at 2.9 A, 2.9 A and 2.2 A resolution, respectively...
  23. Kuriki T, Guan H, Sivak M, Preiss J. Analysis of the active center of branching enzyme II from maize endosperm. J Protein Chem. 1996;15:305-13 pubmed
    ..The importance of the carboxyl amino acid residues was also demonstrated by chemical modification of the branching enzyme protein using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. ..
  24. Nemeth S, Viskupic E, Kvetnansky R, Kolena J. Progressive weakening of the response of key enzymes of liver glycogen metabolism to permanently increased plasma epinephrine levels. Physiol Bohemoslov. 1987;36:441-6 pubmed
    ..5 of epinephrine increased liver phosphorylase a activity within 5 min, whereas later a weakening of the hormone effect was observed...
  25. Zabrocki P, Swiatek W, Sugajska E, Thevelein J, Wera S, Zolnierowicz S. The Saccharomyces cerevisiae type 2A protein phosphatase Pph22p is biochemically different from mammalian PP2A. Eur J Biochem. 2002;269:3372-82 pubmed
    ..Both enzymes displayed similar specific activities with 32P-labelled phosphorylase a as substrate. Furthermore, selected inhibitors and metal ions affected their activities to the same extend...
  26. Kodavanti P, Kodavanti U, Mehendale H. Carbon tetrachloride-induced alterations of hepatic calmodulin and free calcium levels in rats pretreated with chlordecone. Hepatology. 1991;13:230-8 pubmed
    ..during cell division, we have assessed subcellular distribution of calmodulin and estimated cytosolic phosphorylase a to indicate cytosolic free Ca2+ levels in livers of rats fed 0 ppm or 10 ppm (chlordecone) in the diet for 15 ..
  27. Arrese E, Rojas Rivas B, Wells M. Purification and properties of glycogen phosphorylase from the fat body of larval Manduca sexta. Insect Biochem Mol Biol. 1995;25:209-16 pubmed
    ..The molecular mass of phosphorylase a was estimated to be 250,000 Da by gel filtration chromatography...
  28. Cartus T, Heurich R, Drews G, Ammon H. Distribution of protein phosphatases type 1 and 2A in RINm5F cells. Regul Pept. 1998;77:77-81 pubmed
    ..The data suggest that in membrane and nuclear fractions of RINmSF cells predominantly PP1 is present, whereas in the cytosol PP1 as well as PP2A can be detected. ..
  29. Vergauwen L, Richter E, Hespel P. Adenosine exerts a glycogen-sparing action in contracting rat skeletal muscle. Am J Physiol. 1997;272:E762-8 pubmed
    ..It is concluded that adenosine exerts a glycogen-sparing action in oxidative skeletal muscle exposed to both insulin and beta-adrenergic stimulation during contraction, presumably via stimulation of glycogen synthase activity. ..
  30. García Sáinz J, Mendoza Mendoza A. Chloroquine inhibits alpha1B-adrenergic action in hepatocytes. Eur J Pharmacol. 1998;342:333-8 pubmed
    Noradrenaline increased phosphorylase a activity through activation of alpha1B-adrenoceptors in rat hepatocytes...
  31. Dale J, Courtney H, Kotb M, Schifferli D. Phosphorylase-cross-reactive antibodies evoked by streptococcal M protein. Infect Immun. 1990;58:774-8 pubmed
    ..One of the three cross-reactive pep M5 antisera inhibited the enzymatic activity of phosphorylase a in a dose-related fashion, reaching a maximum inhibition of 75%...
  32. García Sáinz J, Macias Silva M. Angiotensin II stimulates phosphoinositide turnover and phosphorylase through AII-1 receptors in isolated rat hepatocytes. Biochem Biophys Res Commun. 1990;172:780-5 pubmed
    Angiotensin II stimulated the activity of phosphorylase a (EC50 approximately 3 nM). The effect of two receptor subtype-selective nonpeptide antagonists, DuP 753 (AII-1 selective) and PD123177 (AII-2 selective), was studied...
  33. Gannon M, Nuttall F. Physiological doses of oral casein affect hepatic glycogen metabolism in normal food-deprived rats. J Nutr. 1995;125:1159-66 pubmed
    ..This was associated with an activation of phosphorylase a and a decrease in hepatic glycogen concentration...
  34. Vanneste Y, Lison D. Biochemical changes associated with muscle fibre necrosis after experimental organophosphate poisoning. Hum Exp Toxicol. 1993;12:365-70 pubmed
    ..Calcium-activated neutral protease and phosphorylase a activities were elevated in the muscle at the same time. 4...
  35. Farkas I, Toth B, Gergely P, Bot G. Insoluble glycogen and its interaction with phosphorylase. A novel method for the purification of liver phosphorylase A. Acta Biochim Biophys Hung. 1987;22:17-29 pubmed
    ..Based on the formation of an insoluble glycogen protein complex sedimentable even by low-speed centrifugation, a novel method has been developed for the purification of liver phosphorylase a in a homogeneous form.
  36. Begum N, Sussman K, Draznin B. Calcium-induced inhibition of phosphoserine phosphatase in insulin target cells is mediated by the phosphorylation and activation of inhibitor 1. J Biol Chem. 1992;267:5959-63 pubmed
    ..The inhibition of PSPases may cause inappropriate serine dephosphorylation of substrates of insulin action resulting in insulin resistance. ..
  37. Cascales M, Martin Sanz P, Alvarez A, Sanchez Perez M, Díez Fernández C, Bosca L. Isoenzymes of carbohydrate metabolism in primary cultures of hepatocytes from thioacetamide-induced rat liver necrosis: responses to growth factors. Hepatology. 1992;16:232-40 pubmed
    ..The lack of response to glucagon of glycogen phosphorylase a and 6-phosphofructo 2-kinase from thioacetamide-treated hepatocytes may indicate that the expression of ..
  38. Aiston S, Coghlan M, Agius L. Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. Eur J Biochem. 2003;270:2773-81 pubmed
    ..kinase-3 (GSK-3) and an allosteric inhibitor of phosphorylase (CP-91149) that causes dephosphorylation of phosphorylase a, to determine the relative contributions of inactivation of GSK-3 and dephosphorylation of phosphorylase a as ..
  39. Molenaar P, Savarimuthu S, Sarsero D, Chen L, Semmler A, Carle A, et al. (-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through beta2 -adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling. Naunyn Schmiedebergs Arch Pharmacol. 2007;375:11-28 pubmed
    ..Activation of beta2 -adrenoceptors caused an increase in phosphorylase a activity in atrium from failing hearts further emphasizing the presence of the beta2 -adrenoceptor-Gsalpha-..
  40. Zhang J, Lindup W. Cisplatin-induced nephrotoxicity in vitro: increases in cytosolic calcium concentration and the inhibition of cytosolic and mitochondrial protein kinase C. Toxicol Lett. 1996;89:11-7 pubmed
    Exposure of rat kidney cortical slices to cisplatin (2 mM) significantly increased the activity of cytosolic phosphorylase a, indicating that the concentration of cytosolic Ca2+ was increased...
  41. Jozwik M, Sledziewski A, Jasiewicz A, Sajewska G, Kozanecki A. [Effect of diseases in pregnancy on certain placental functions. Enzymatic systems degrading placental glycogen in pregnancy with gestosis]. Probl Med Wieku Rozwoj. 1990;16:137-42 pubmed
    ..In placentas derived from gestotic cases elevated activity of phosphorylase A, the decrease in phosphorylase B activity and the rise in glucoamylase were found...
  42. Salas V, Corcoran G. Calcium-dependent DNA damage and adenosine 3',5'-cyclic monophosphate-independent glycogen phosphorylase activation in an in vitro model of acetaminophen-induced liver injury. Hepatology. 1997;25:1432-8 pubmed
    ..The status of cytosolic Ca2+ was determined by measuring Ca2+-dependent activation of glycogen phosphorylase a. Primary cultures of mouse hepatocytes exposed to a toxic concentration of APAP showed twofold and greater ..
  43. Bouscarel B, Wilson P, Blackmore P, Lynch C, Exton J. Agonist-induced down-regulation of the angiotensin II receptor in primary cultures of rat hepatocytes. J Biol Chem. 1988;263:14920-4 pubmed
    ..e. calcium and cAMP. ..
  44. Tamrakar S, Ludlow J. The carboxyl-terminal region of the retinoblastoma protein binds non-competitively to protein phosphatase type 1alpha and inhibits catalytic activity. J Biol Chem. 2000;275:27784-9 pubmed
    ..biochemical analyses demonstrated inhibition of PP1 catalytic activity toward the standard substrate phosphorylase a when this enzyme is bound to pRB containing this region...
  45. Ercan Fang N, Nuttall F, Gannon M. Uric acid inhibits liver phosphorylase a activity under simulated in vivo conditions. Am J Physiol Endocrinol Metab. 2001;280:E248-53 pubmed
    ..that glycogen synthesis and degradation can occur in vivo without a significant change in the amount of phosphorylase a present...
  46. Ren J, Hultman E. Regulation of glycogenolysis in human skeletal muscle. J Appl Physiol (1985). 1989;67:2243-8 pubmed
    ..The study was performed with and without infusion of epinephrine (EPI). In the absence of EPI the phosphorylase a fraction was 50% immediately at the end of the initial stimulation period, declining to 22% after 60 s...
  47. Dombradi V, Willis A, Vereb G, Johnson L. The sequence around the phosphorylation site of the porcine heart type phosphorylase isoenzyme. Comp Biochem Physiol B. 1988;91:717-21 pubmed
    1. A tetradecapeptide containing the phosphorylation site was obtained from 32P-labelled pig heart phosphorylase a isoenzyme by alpha-chymotryptic digestion. 2...
  48. Mayer D, Bannasch P. Activity of glycogen synthase and phosphorylase and glucose 6-phosphate content in renal clear cell carcinomas. J Cancer Res Clin Oncol. 1988;114:369-72 pubmed
    ..The activities of phosphorylase a and b as well as of synthase R and D were also increased. Synthase I activity, however, was reduced...
  49. Bartel S, Krause E, Wallukat G, Karczewski P. New insights into beta2-adrenoceptor signaling in the adult rat heart. Cardiovasc Res. 2003;57:694-703 pubmed
    ..significant CaM kinase II-related Thr17 phosphorylation, troponin I phosphorylation and activation of phosphorylase a. Our findings clearly show that beta(2)-adrenoceptor signaling is coupled to phospholamban phosphorylation ..
  50. Horton A, Wood J. Effects of inhibitors of phospholipase A2, cyclooxygenase and thromboxane synthetase on paracetamol hepatotoxicity in the rat. Eicosanoids. 1989;2:123-9 pubmed
    ..The data presented support the proposed sequence of events in which A.A., released from membrane phospholipids by Ca2(+)-activated PLA2, acts as substrate for the synthesis of cytodestructive eicosanoids. ..
  51. Burcham P, Harman A. Paracetamol-induced stimulation of glycogenolysis in isolated mouse hepatocytes is not directly associated with cell death. Biochem Pharmacol. 1989;38:2357-62 pubmed
    ..Concentrations of paracetamol that produced plasma membrane damage were also found to activate glycogen phosphorylase a and deplete cellular glycogen contents...
  52. Kauffman F, Davis L, Whittaker M. Activation of glycogen phosphorylase in rat pheochromocytoma PC12 cells and isolated hepatocytes by organophosphates. Biochem Pharmacol. 1990;39:347-54 pubmed
    ..Collectively, these data argue strongly that organophosphates increase phosphorylase-a activity in intact cells via a novel mechanism involving release of calcium from intracellular binding sites. ..
  53. Christopher M, Sleeman M, Alford F, Best J. Contrasting action of short- and long-term adrenaline infusion on dog skeletal muscle glucose metabolism. Diabetologia. 1992;35:399-405 pubmed
    ..Acutely, phosphofructokinase had reduced Vmax (short-term adrenaline 34 +/- 6 vs NaCl 44 +/- 5 U/g; p less than 0.05) but was still above the maximal operating rate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) ..