Release of Brain Mitochondrial Hexokinase by Acidic Proteins and Macromolecular Polyanions

Preparations of arachidonic acid binding and non-binding proteins from bovine brain, four acidic proteins ("-casein, phosvitin, $-lactoglobulin A and B), the peptide polyglutamate, and two polyanions (heparin, dextran sulfate) enhanced both basal and glucose 6-phosphate induced solubilization of rat brain mitochondrial hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1). In contrast, three other acidic proteins, had little ("-lactalbumin) or no effect (bovine serum albumin, ovalbumin) and five basic proteins inhibited release of the enzyme. Solubilizing activity therefore appears to require a net negative charge and one or more of the following structural features: extended conformation, random coil, unordered or $-structure, in this case the $-barrel in the fatty acid binding proteins and $-lactoglobulins. It is of interest that a difference of a single negative charge between $-lactoglobulin A and B, resulted in a statistically significant difference in the stimulation of hexokinase release. Possible physiological and pathological roles of this solubilizing effect are discussed briefly.