Glycogen metabolism Kinase-activating factor

The multifimctional CaM kinases are collectively referred to as CaM kinases of type II, whereby further subtypes a, p, y and 6 are differentiated. The a and P subtypes of CaM kinase II only occur in the brain whereas the other subtypes are also found in other organs. The multifunctional CaM kinases regulate many processes (see Table 7.1) such as glycogen metabolism, activity of transcription factors, microfilament formation, synaptic release of neurotransmitters from storage vesicles, biosynthesis of neurotransmitters and many more. An important cellular function is assigned to CaM kinase II in brain, where it makes up 0.25 % of the total protein. 

Of the protein kinases, protein kinase A is the best investigated and characterized (review Francis and Corbin, 1994). The functions of protein kinase A are diverse. Protein kinase A is involved in the regulation of metabolism of glycogen, lipids and sugars. Substrates of protein kinase A may be other protein kinases, as well as enzymes of intermediary metabolism. Protein kinase A is also involved in cAMP-stimulated transcription of genes that have a cAMP-responsive element in their control region (review Montminy, 1997). An increase in cAMP concentration leads to activation of protein kinase A which phosphorylates the transcription factor CREB at Ser 133. CREB only binds to the transcriptional coactivator CBP in the phosphorylated state and stimulates transcription (see Chapter 1.4.4.2). 

Epinephrine is a hormone that causes extremely rapid responses. One of the responses to this hormone is an increased liberation of liver glycogen as glucose. This reaction has been found to be limited by the enzyme phosphorylase. Liver phosphorylase exists as the active enzyme and as the inactive, dephosphophosphorylase. Epinephrine, and also the hyperglycemic factor, glucagon, have been found to stimulate the formation of active phosphorylase. This stimulation is mediated by an adenine nucleotide liberated from cell particles by an action of the hormones. The liberation of the nucleotide has been demonstrated in cell-free systems. The nucleotide in an unexplained manner, perhaps indirectly or after metabolic conversion to another form, alters the activity of either the kinase or the phosphatase so that the steady-state concentration of active phosphorylase is increased, i ... 

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