Kinase phosphorylase

B. Ca -calmodnlin (CaM)-dependent Phosphorylase kinase (PhK) —krk qis vrgl— phosphorylation by PKA... 

Stimulation of glycogen breakdown involves consumption of molecules of ATP at three different steps in the hormone-sensitive adenylyl cyclase cascade (Figure 15.19). Note that the cascade mechanism is a means of chemical amplification, because the binding of just a few molecules of epinephrine or glucagon results in the synthesis of many molecules of cyclic / MP, which, through the action of c/ MP-dependent protein kinase, can activate many more molecules of phosphorylase kinase and even more molecules of phosphorylase. For example, an extracellular level of 10 to 10 M epinephrine prompts the for-... 

MP, approximately 30 phosphorylase kinase molecules are activated these in turn activate some 800 molecules of phosphorylase. Each of these catalyzes the formation of many molecules of glucose-l-P. 

A decreased glycolytic rate has been proposed as a cause of muscle fatigue and related to pH inhibition of glycolytic enzymes. Decreasing pH inhibits both phosphorylase kinase and phosphofructokinase (PFK) activities. PFK is rate determining for glycolytic flux and therefore must be precisely matched to the rate of ATP expenditure. The essential characteristic of PFK control is allosteric inhibition by ATP. This inhibition is increased by H and PCr (Storey and Hochachka, 1974 ... 

In hver, one of the serine hydroxyl groups of active phosphorylase a is phosphorylated. It is inactivated by hydrolytic removal of the phosphate by protein phos-phatase-1 to form ph osphorylase h. Reactivation requires rephosphorylation catalyzed by phosphorylase kinase. 

Glycogenolysis increases in muscle several hundred-fold immediately after the onset of contraction. This involves the rapid activation of phosphorylase by activation of phosphorylase kinase by Ca +, the same signal as that which initiates contraction in response to nerve stimulation. Muscle phosphorylase kinase has four... 

Both phosphorylase a and phosphorylase kinase a are dephosphorylated and inactivated by protein phos-phatase-1. Protein phosphatase-1 is inhibited by a protein, inhibitor-1, which is active only after it has been phosphorylated by cAMP-dependent protein kinase. Thus, cAMP controls both the activation and inactivation of phosphorylase (Figure 18-6). Insulin reinforces this effect by inhibiting the activation of phosphorylase b. It does this indirectly by increasing uptake of glucose, leading to increased formation of glucose 6-phosphate, which is an inhibitor of phosphorylase kinase. 

Not only is phosphorylase activated by a rise in concentration of cAMP (via phosphorylase kinase), but glycogen synthase is at the same time converted to the inactive form both effects are mediated via cAMP-dependent protein kinase. Thus, inhibition of glycogenolysis enhances net glycogenesis, and inhibition of glycogenesis enhances net glycogenolysis. Furthermore,... 

Type VIII Deficiency of liver phosphorylase kinase As for type VI. 

NARDINI M, SCACCINI c, PACKER L and VIRGILI F (2000) In vivo inhibition of the activity of phosphorylase kinase, protein kinase C and protein kinase A by caffeic acid and a procyanidin rich pine bark (Pinus maritima) extract Biochimica Biophysica Acta 1474, 219-25. 

Protein phosphorylation Calmodulin kinase I ATI Elongation factor-2 kinase Phosphorylase kinase Myosin Light Chain kinase... 

SIGNAL INTEGRATION by phosphorylase kinase. Phosphorylase kinase eventually phosphorylates and activates glycogen phosphorylase. Either (or both) phosphorylation and calcium signaling pathways converge at phosphorylase kinase. 

Secondary signals Glucose 6-phosphate activates synthesis. Ca2+-Calmodulin activates degradation by activating phosphorylase kinase. 

The remaining three types of CaMK are phosphorylase kinase, myosin light-chain kinase and CaMKIII. These each appear to phosphorylate fewer substrate proteins, and in some cases only one protein, under physiological conditions, and each may therefore mediate relatively fewer actions of Ca2+ in the nervous system. 

In liver phosphorylase deficiency (glycogenosis type VI, Hers disease Fig. 42-1) and in two genetic forms of phosphorylase kinase deficiency, one of which is X-linked recessive, the other of which is autosomal recessive, hypoglycemia is either absent or mild. Symptoms of brain dysfunction do not usually occur (type VIII, Fig. 42-1) [1],... 

Glycogen phosphorylase isoenzymes have been isolated from liver, brain and skeletal muscle. All forms are subject to covalent control with conversion of the inactive forms (GP-b) to the active forms (GP-a) by phosphorylation on specific serine residues. This phosphorylation step, mediated by the enzyme phosphorylase kinase, is initiated by glucagon stimulation of the hepatocyte. Indeed, the same cAMP cascade which inhibits glycogen synthesis simultaneously stimulates glycogenolysis, giving us an excellent example of reciprocal control. 

Calcium ions released from the SR are required to initiate contraction and activate glycogen phosphorylase kinase... 

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