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 Km
glucose for
hexokinase from the anoxic animal suggests a more active
enzyme form during
anoxia. Conversely, in the foot muscle, an increase in Km
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 Km
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 Km
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.