Phosphorylases kinase active, inactive

The rate of activation of phosphorylase is measured at pH 6.0 or 6.8 and pH 8.2, and the result is expressed as the ratio of phosphorylase kinase activity measured at the low pH to that measured at the high pH. An increase in the activity ratio of phosphorylase kinase indicates transformation to the activated (phosphorylated) form of the enzyme. Activated phosphorylase kinase is 25 to 50 times more active than inactive phos-... 

Phosphorylase phosphorylation is catalyzed by phosphorylase kinase. Phosphorylase kinase is inactive in a nonphosphorylated state and active when phosphorylated. Phosphorylase kinase phosphorylation is catalyzed by the cAMP-dependent protein kinase. 

Phosphorylase kinase (now inactive) Phosphorylase kinase (now active)... 

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,... 

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. 

The next key point is to realize that each enzyme in the pathway exists in both active and inactive forms. cAMP initiates a cascade of reactions by activating protein kinase A (PK-A)," the active form of which activates the next enzyme in the sequence, and so on. At the end of the day, glycogen phosphorylase is activated and glucose or ATP is produced. This signaling pathway is a marvelous amplification system. A few molecules of glucagon or adrenaline may induce formation of many molecules of cAMP, which may activate many of PK-A, and so on. The catalytic power of enzymes is magnified in cascades of this sort. 

Fig. 7.18. Regulation of glycogen metabolism in muscle. Phosphorylase kinase stands at the center of regulation of glycogen metabolism. Phosphorylase kinase may exist in an active, phosphorylated form and an inactive, unphosphorylated form. Phosphorylation of phosphorylase kinase is triggered by hormonal signals (e.g. adrenahne) and takes place via an activation of protein kinase A in the cAMP pathway. In the absence of hormonal stimulation, phosphorylase kinase can also be activated by an increase in cytosolic Ca. The active phosphorylase kinase stimulates glycogen degradation and inhibits glycogen synthesis, in that, on the one side, it activates glycogen phosphorylase by phosphorylation, and on the other side, it inactivates glycogen synthase by phosphorylation.

Activation of phosphorylase kinase Phosphorylase kinase exists in two forms an inactive "b" form and an active "a" form. Active cAMP-dependent protein kinase phosphorylates the inactive form of phosphorylase kinase, resulting in its activation (see Figure... 

A metabolite acting as an allosteric effector turns on an enzyme that either acts directly on that metabolite or acts on a product that lies further ahead in the sequence. For example, in Fig. 11-1, metabolite C activates the enzyme that catalyzes an essentially irreversible reaction of compound D. An actual example is provided by glycogen synthase, whose inactive "dependent" or D form is activated allosterically by the glycogen precursor glucose 6-phosphate.39 See also phosphorylase kinase (Section 2). 

Cyclic AMP triggers a cascade of reactions that ultimately lead to glycogen breakdown. The immediate action of cAMP is to activate a protein kinase that phosphorylates a number of proteins, including phosphorylase kinase. Phosphorylation of phosphorylase kinase converts it from an inactive to an active form, which catalyzes the conversion of phosphorylase b to phosphorylase a (see chapter 9). The cascade of effects triggered by glucagon is shown in figure 12.29. 

Phosphorylase exists in two interchangeable forms active phosphorylase a and a normally inactive phosphorylase b. Phosphorylase b is a dimer and is converted into phosphorylase a by phosphorylation of a single serine residue on each subunit by the enzyme phosphorylase kinase. The process can be reversed and phosphorylase inactivated by removal of the phosphate group by protein phosphatase I (Fig. 2a) (see Topic C5). 

Phosphorylase kinase is one of the best characterized enzyme systems to illustrate the role of calcium ions in regulation of intermediary metabolism. Phosphorylase kinase is composed of four different subunits termed a (Mr 145000), /3 (MT 128000), y (A/r 45000) and 5 (Mr 17000) and has the structure (a/3y8)A [106]. Only one of its four subunits actually catalyses the phosphorylation reaction the other three subunits are regulatory and enable the enzyme complex to be activated both by calcium and cyclic AMP. The y subunit carries the catalytic activity the 8 subunit is the calcium binding protein calmodulin and is responsible for the calcium dependence of the enzyme. The a and /3 subunits are the targets for cyclic-AMP mediated regulation, both being phosphorylated by the cyclic-AMP dependent protein kinase. Calmodulin appears to interact with phosphorylase kinase in a different manner from other enzymes, since it is an integral component of the enzyme. Phosphorylase kinase has an absolute requirement for calcium, and is inactive in its absence. 

Rabbit muscle phosphorylase can exist in two forms an essentially inactive dimer, phosphorylase b, and an active tetramer, phosphorylase a. When AMP is noncovalently bound to phosphorylase b. or when phosphorylase b is phosphorylated at a serine residue by phosphorylase kinase, the enzyme is converted to the active, predominantly tetrameric, form (Chap. 11). The reaction can be reversed by the removal of AMP or the dephosphorylation of serines by phosphorylase phosphatase. 

Finally, the active phosphorylase kinase converts the inactive form of another enzyme, phosphorylase b, into its active form, phosphorylase a (Fig. 11-25). 

The phosphorylase kinase converts an inactive, non- phosphorylated form, glycogen phosphorylase bto an active, phosphorylated form, phosphorylase a. 

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