Regulatory Properties of Soluble and Particulate Rat Brain Tyrosine Hydroxylase

Abstract

Abstract Rat brain tyrosine hydroxylase exists in two distinct physical forms, a soluble and a membrane-bound form. The two forms are brain-region specific, with the membrane-bound or particulate form predominating in the striatum, an area enriched in catecholamine nerve endings and associated with a specific membrane fraction. Whereas the soluble and the particulate enzymes exhibit an identical Km for the substrate tyrosine (0.055 mm), the particulate form, which can be simulated by the addition to the soluble enzyme of microgram amounts of the sulfated mucopolysaccharide heparin, has a lower Km (0.15 mm) for the synthetic co-factor 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH4) than does the soluble (0.75 mm) and a 2-fold increased apparent Vmax. The particulate enzyme also has a greater affinity for the competitive feedback inhibitors norepinephrine and 3,4-dihydroxyphenylethylamine (dopamine). Dopamine exhibits a greater affinity for both forms of the enzyme than norepinephrine and, in addition, dopamine but not norepinephrine induces cooperative DMPH4 kinetics in soluble but not particulate tyrosine hydroxylase. It is suggested that dopamine may be the more significant regulatory metabolite of the striatal biogenic amine biosynthetic pathway, and that tyrosine hydroxylase activity may be regulated by alterations in the physical state of the enzyme.