Abstract
Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent Km value for 6-methyltetrahydropterin. Removal of endogenous catecholamines by gel filtration or cation exchange results in a similar activation. Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine Ki value. None of the above treatments appears to change the molecular weight of the enzyme. At physiological concentrations of dopamine, the increase in Ki by phosphorylation would effectively release tyrosine hydroxylase from end product feedback inhibition.
Highlights
Heart, Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent K, value for 6
(3) indicates that gel filtration of crude striatal extracts causes a decrease in the apparent K, of tyrosine hydroxylase for 6-methyltetrahydropterin (GMPH,)
The activation of tyrosine hydroxylase has been demonstrated by a number of experimental techniques including phosphorylation of tissue extracts (2, 3), treatment of animals with neuroleptics (4, 91, gel filtration of extracts (31, and exposure of tissue extracts to polyanions and salts (6, 11, 12)
Summary
Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent K,,, value for 6-. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine K, value. Short term regulation of the enzyme is effected by alterations in its kinetic state (2, 3), often by a change in the apparent affinity of the enzyme for its pterin cofactor (2-6). This is significant in that the tissue concentration of the cofactor is low enough to limit the activity of the unstimulated enzyme (7, 8). As well as the possibility of regulatory factors being present in the tissue milieu, we felt it important to use the nonpurified extracts
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