Hexokinase from the hepatopancreas and foot muscle of Littorina littorea undergoes stable modification of its kinetic and structural properties in response to prolonged oxygen deprivation. In the hepatopancreas, a reduction in the K_m glucose for hexokinase from the anoxic animal suggests a more active enzyme form during anoxia. Conversely, in the foot muscle, an increase in K_m ATP and a decrease in Vmax for anoxic snail hexokinase were consistent with a less active enzyme form during anoxia. In either case, the molecular basis for the stable modification of hexokinase kinetics is reversible phosphorylation. The activation of endogenous PKC and AMPK increased the K_m glucose for anoxic hepatopancreas hexokinase to a value that was similar to the control Km glucose. Alternatively, stimulation of endogenous PKA, PKG, and CamK for control foot muscle hexokinase increased the K_m ATP to a value similar to that seen for the anoxic enzyme form. In both tissues, activation of endogenous phosphatases reversed the effects of protein kinases. Dephosphorylation and activation of hepatopancreas hexokinase during anoxia may allow for increased shunting of glucose-6-phosphate into the pentose phosphate pathway, thereby producing reducing equivalents of NADPH needed for antioxidant defense upon tissue re-oxygenation. Conversely, phosphorylation and inhibition of foot muscle hexokinase during anoxia may reflect the decreased need for glucose oxidation during hypometabolism.
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