PHK
The PHK group denotes phosphorylase kinase, the archetypal calcium/calmodulin-dependent kinase discovered through its control of glycogen breakdown. The enzyme is a hexadecamer of four different subunits arranged as an alpha-beta-gamma-delta tetramer repeated four times, where gamma carries catalytic activity, delta is calmodulin, and alpha and beta are regulatory. In muscle, contraction-released calcium activates PHK, which phosphorylates glycogen phosphorylase b to the active a form and inactivates glycogen synthase, synchronizing energy supply with contractile demand. Liver isoforms mediate glucagon-stimulated glycogenolysis. Mutations in regulatory subunits cause glycogen storage disease type IX, presenting with exercise intolerance, hepatomegaly, or liver dysfunction depending on the affected subunit and tissue.
