The Effect of Phenylalanine Metabolites on the Binding of HK-I (Hexokinase Type I) to Rat ́s Brain Mitochondria

Hexokinase type I is the most predominant form of the enzyme in brain. It binds reversibly to the outer mitochondria membrane. In normal condition the major part of the enzyme binds to the membrane. Membrane bound form of the enzyme is more active than the soluble form, so this is more a control mechanism of the enzyme activity. Those metabolites that affect the binding or releasing of the enzyme from the mitochondria have regulatory effect on glucose consumption of the cell. Since an increase in phenylalanine and its metabolites causes mental retardation in patients with phenylketonuria, we have studied the effects of these metabolites on the activity, binding and releasing of the enzyme to determine the destructive effect of these metabolites in relation to glucose metabolism in brain. This investigation was an experimental study in which hexokinase activity was determined spectrophotometrically by using G6PD(Glucose-6-Phosphate Dehydrogenase) coupled assay. The results show that phenylpyruvic acid decreases the enzyme activity in bound and soluble forms and increases the release of the enzyme from mitochondria whereas phenylalanine and phenyllactic acid have no effect on the enzyme activity, release and rebinding. It is possible that phenylpyruvic acid causes the reduction of glucose consumption by decreasing hexokinase activity. Therefore, ATP(Adenosine Triphosphate) production declines in brain cells.