REGIONAL AND SUBCELLULAR DISTRIBUTION AND KINETIC PROPERTIES OF RAT BRAIN CHOLINE ACETYLTRANSFERASE–SOME FUNCTIONAL CONSIDERATIONS

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Abstract
—: The kinetic properties of soluble and membrane‐bound choline acetyltransferase (ChAc) were determined as a function of homogenization media and solubilization procedure in various regions of rat brain. Treatment of homogenate and/or subcellular fractions with KCl, Triton X‐100, or ether dramatically altered the apparent Vmax and the degree of solubilization of the enzyme, but no fraction exhibited Km values substantially different from 12 μM for acetyl‐CoA and 200 μM for choline. On the other hand, increasing the ionic strength of the assay medium for a given fraction from 0‐02 M to 0‐5 M increased both Vmax and Km values for both substrates. The absolute levels and subcellular distribution of ChAc were determined in 11 brain regions to localize cholinergic cell bodies and nerve endings. Levels of ChAc varied from 139 m‐units/g tissue in caudate‐putamen to 5‐7 m‐units/g tissue in cerebellum. The fraction of ChAc activity associated with synaptosomes varied from near 75 per cent in caudate‐putamen, hippocampus and cortical regions to near 20 per cent in septum, locus coeruleus area and substantia nigra area. The apparent parallel distribution of cholinergic and catecholaminergic nerve endings is discussed in terms of a hypothetical model for the pathophysiology and treatment of Parkinson's syndrome.