The regulation of muscle phosphorylase kinase by calcium ions, calmodulin and troponin-C.
Although it has been believed for several years that calcium ions are the means by which glycogenolysis and muscle contraction are synchronized, it is only over the past three years that this concept has started to be placed on a firm molecular basis. It appears that the regulation of phosphorylase kinase in vivo is achieved through the interaction of the enzyme with the two calcium binding proteins, calmodulin and troponin-C, and that the relative importance of these proteins depends on the degree of phosphorylation of the enzyme (figure 3). In the dephosphorylated form of the enzyme, troponin-C rather than calmodulin is the dominant calcium dependent regulator providing an attractive mechanism of coupling glycogenolysis and muscle contraction, since the same calcium binding protein activates both processes. On the other hand, the phosphorylated form of the enzyme can hardly be activated at all by troponin-C, although it is still completely dependent on calcium ions. Calmodulin (the delta-subunit) is therefore the dominant calcium dependent regulator of phosphorylase kinase in its hormonally activated state. Recent work has demonstrated that phosphorylase kinase not only activates phosphorylase, but also phosphorylates glycogen synthase thereby decreasing its activity (45-49). The regulation of phosphorylase kinase by calcium ions may therefore also provide a mechanism for co-ordinating the rates of glycogenolysis and glycogen synthesis during muscle contraction.
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000502:physiology*; D009132:Muscles / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits; D014336:Troponin / Q000502:physiology*; D019209:Troponin C
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D009124:Muscle Proteins; D014336:Troponin; D019209:Troponin C; D006003:Glycogen; D010764:Phosphorylase Kinase; D002118:Calcium