Protein kinase metabolic role

Not included are other protein kinases present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that may not play a role in neuron-specific phenomena. CAK, CDK-activating kinase ... 

Phosphoryl group transfer reactions add or remove phosphoryl groups to or from cellular metabolites and macromolecules, and play a major role in biochemistry. Phosphoryl transfer is the most common enzymatic function coded by the yeast genome and, in addition to its importance in intermediary metabolism (see Chapter 5), the reaction is catalysed by a large number of central regulatory enzymes that are often part of signalling cascades, such as protein kinases, protein phosphatases, ATPases and GTPases. 

The switch in the action of the enzyme between its kinase and phosphatase activities is brought about by phosphorylation mediated by the serine/threonine protein kinase A (PKA), the same cAMP dependent enzyme which plays a role in the control of glycogen metabolism. In its kinase form, PFK-2 is dephosphorylated but phosphorylated in the phosphatase form. 

The membrane-associated Akt kinase is now a substrate for protein kinase PDKl that phosphorylates a specific Thr and Ser residue of Akt kinase. The double phosphorylation converts Akt kinase to the active form. It is assumed that the Akt kinase now dissociates from the membrane and phosphorylates cytosolic substrates such as glycogen synthase kinase, 6-phosphofructo-2-kinase and ribosomal protein S6 kinase, p70 . According to this mechanism, Akt kinase regulates central metabolic pathways of the cell. Furthermore, it has a promoting influence on cell division and an inhibitory influence on programmed cell death, apoptosis. A role in apoptosis is suggested by the observation that a component of the apoptotic program. Bad protein (see Chapter 15) has been identified as a substrate of Akt kinase. 

New discussion of the role of AMP-dependent protein kinase in metabolic integration... 

Vanadium. Vanadium is essential in rats and chicks. Estimated human intake is less than 4 mg/d. In animals, deliciency results in impaired growth, reproduction, and lipid metabolism, and altered thyroid peroxidase activities. Vanadium may play a role in the regulation of INaK)-ATPase. phosphoryl transferases, adenylate cyclase, and protein kinases. 

Whiteman EL, Cho H, Birnbaum MJ. 2002. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab 13 444-451. 

Winder, W. W., and Hardie, D. G. 1999. AMP-activated protein kinase, a metabolic master switch possible roles in type 2 diabetes. Am. J. Physiol. 277 E1-E10. 

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. 

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