Brain hexokinase. A proposed relation between soluble-particulate distribution and activity in vivo.

Abstract The particulate hexokinase activity of rat brain is interconvertible among soluble, particulate, and latent (also particulate) forms. Changes in the distribution of the enzyme among these forms may be effected by changes in levels of certain common metabolites in the incubation medium. Glucose-6-P, ATP, ADP, AMP, various chelating agents, and high salt concentrations cause solubilization, and ATP, ADP, and glucose-6-P also cause a partial exposure of the latent activity. Solubilization by glucose-6-P and ATP is relatively specific for hexokinase compared to solubilization by high salt concentrations. The solubilization by glucose-6-P is reversed by divalent cations and inhibited by Pi, while solubilization by ATP is not affected by these agents. Solubilization by ATP and glucose-6-P also differ in their sensitivity to temperature changes. Results are presented which are interpreted as indicating the existence of four pools of particulate hexokinase activity in rat brain, defined by their susceptibility to exposure and solubilization (or both) by ATP, glucose-6-P, and Triton X-100. It is suggested that these pools result primarily from differences in the intracellular location of the enzyme. It is proposed that hexokinase activity in vivo may be controlled by the relative distribution between soluble and particulate forms, the latter being more active. This distribution is considered to be governed by the intracellular ATP, glucose-6-P, and Pi (and possibly other metabolite) levels. The proposed increased activity of the particulate enzyme may be due, at least in part, to increased affinity for ATP, as measured by the Km value for this substrate, and decreased susceptibility to inhibition by glucose-6-P.