Phosphorylase phosphatase and

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. 

Physiologic effect Inhibition of ion conductance Repetitive firing, shift of voltage dependence of activation Inhibition of phosphorylase phosphatases 1 and 2a Receptor-induced depolarization and excitation Unknown Ciguatoxin repetitive firing, shift of voltage dependence of activation Maitotoxin calcium ion influx... 

The principle underlying the changes in activity of a G-protein is similar to that of an interconversion cycle (Chapter 3). The classic example of an interconversion cycle is that between the two forms of the enzyme phos-phorylase phosphorylase a and b. The interconversions between b and a are catalysed by a protein kinase and a protein phosphatase. The similarities are as follows. 

Phosphatases and nucleotidases Nucleoside phosphorylases and hydrolases Deaminases Oxidases Summary... 

It had been known from at least the time of Pasteur that the presence of sodium or potassium phosphate aided the progress of a yeast fermentation. Later intensive study showed that a complex group of enzymes (phosphatases and phosphorylases) was responsible for the phosphorylation, dephosphorylation and interconversion of D-glucose 6-phosphate, D-fructose 6-phosphate, D-fructose 1,6-diphosphate and similar substances in various types of cells and muscle tissue. Detailed reviews of the field are available. - A further advance was made in 1936, when Cori and Cori noted that in certain circumstances well-washed frog muscle immersed in a sodium phosphate buffer utilized the inorganic phosphate to produce a new hexose phosphate (the Cori ester). This compound was later shown to be a-D-glucopyranose-l-phosphate and yielded crystalline dipotassium and brucine salts. The Cori ester arose because... 

The examples of phosphorylase kinase and protein phosphatase I illustrate some important principles of regulation of enzyme activity by phosphorylation and dephosphorylation events. They clearly indicate how different signal transduction paths can meet in key reactions of metabolism, how signals can be coordinated with one another and how common components of a regulation network can be activated by different signals. The following principles are highlighted ... 

Synthases and Synthetases Ligases and Lyases Kinases, Phosphatases, and Phosphorylases Yes, the Names Are Confusing ... 

The 5-nitrofuryl group225 is promulgated as an efficacious moiety to ensure chemotherapeutic value, and the trans derivative (135) was found to be active against Staphylococcus aureus,171 It is also a broad-spectrum antimicrobial agent226 and an antischistosomal drug.227 The latter activity is due to reduction of the phosphorylase phosphatase in the worms themselves, damaging reproduction in the female.227, 228... 

The active sites of these enzymes can have a nitrogen ligand, usually as histidine (acid phosphatases and some protein phosphatases), a nucleophilic serine residue (alkaline phosphatases), a cysteine residue in which the thiol group can form a covalent species with the phosphate ester (protein phosphatases), or an aspartate-linked phosphate (plasma membrane ion pumps). The inhibitory form of vanadium is usually anionic vanadate V(V), but cationic vanadyl V(IV) has also shown strong inhibition of some types of phosphorylase reactions. Above neutral pH, speciation of vanadyl ions produces anionic V(IV) species capable of inhibition of enzymes in the traditional transition-state analogue manner [5],... 

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). 

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