Dephosphorylation mechanisms

Hasbi, A., Allouche, S., Sichel, F., et al. (2000) Internalization and recycling of delta-opioid receptor are dependent on a phosphorylation-dephosphorylation mechanism. J. Biol. Chem. 293, 237-247. 

A well-known example, indeed the first enzyme that was shown to be regulated by the phosphorylation/ dephosphorylation mechanism, is glycogen phosphorylase, which catalyses the breakdown of glycogen (Box 3.7). 

Within many tissues the enzymatic activities of the pyruvate and branched chain oxoacid dehydrogenases complexes are controlled in part by a phosphorylation -dephosphorylation mechanism (see Eq. 17-9). Phosphorylation of the decarboxylase subunit by an ATP-dependent kinase produces an inactive phosphoenzyme. A phosphatase reactivates the dehydrogenase to complete the regulatory cycle (see Eq. 17-9 and associated discussion). The regulation is apparently accomplished, in part, by controlling the affinity of the protein for... 

Still other enzymes are regulated essentially in on-off fashion. Pyruvate dehydrogenase (PDH), for example, is regulated by phosphorylation-dephosphorylation mechanisms (by protein kinases and protein phosphatases, respectively). The ATP-dependent PDH... 

Regulation of Pyruvate Dehydrogenase Activity Pyruvate dehydrogenase is the key enzyme that commits pyruvate (and hence the products of carbohydrate metabolism) to complete oxidation (via the tricarboxyUc acid cycle) or lipogenesis. It is subject to regulation by both product inhibition and a phosphorylation/dephosphorylation mechanism. Acetyl CoA and NADH are both inhibitors, competing with coenzyme A and NAD+. 

These two processes are catalyzed by two enzyme activities on the same protein. These two enzyme activities are controlled by a phosphorylation/ dephosphorylation mechanism. Phosphorylation activates the enzyme that degrades F2,6P whereas dephosphorylation activates the enzyme that produces it. 

The concentration of fructose-2,6- wphosphate in a cell depends on the balance between its synthesis (catalyzed by phosphofructokinase-2) and its breakdown (catalyzed by fructose 6i.jphosphatase-2). The separate enzymes that control the formation and breakdown of fructose-2,6-Msphosphate are themselves controlled by a phosphorylation/dephosphorylation mechanism. 

Phosphate esters play an essential part in photosynthesis, carbohydrate and lipid metabolism, the nitrogen cycle and in many other biochemical reactions where they are the principal source of energy transfer. Most, if not all enzyme action, is associated with phosphorylation-dephosphorylation mechanisms. 

This ph osphorylation/dephosphorylation mechanism of control is known as covalent modification (183). 

It is outside the scope of this chapter to discuss the phosphorylation-dephosphorylation mechanisms of individual proteins. It is only possible here to discuss the system in general terms. 

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