MULTIPLE FORMS OF THE ENZYME GLYCEROPHOSPHODIESTERASE ARE PRESENT IN HUMAN BRAIN

Brain levels of glycerophosphodiesters, including glycerophosphocholin e (GPC) and glycerophosphoethanolamine (GPE), are altered in many huma n central nervous system disorders. Although much information is avail able on the enzymes responsible for the formation of these phospholipi d metabolites, little information is known regarding their catabolism, by glycerophosphodiesterases, in human brain. In both autopsied and b iopsied temporal cortex, a phosphocholine-producing glycerophosphodies terase activity was observed. In the presence of 1 mM EDTA, the enzyme possessed a pH optimum of 9.0, while the addition of 5 mM zinc acetat e shifted the pH optimum to 10.5. When assayed at pH 9.0 in the absenc e of zinc acetate, the K-m and V-max were 104 +/- 2 mu M acid 77 +/- 1 8 nmol/h/mg protein, respectively, while assaying at pH 10.5 in the pr esence of 5 mM zinc acetate yielded a K-m of 964 +/- 56 mu M, and a V- max of 534 +/- 114 nmol/h/mg protein. Furthermore, whereas submillimol ar concentrations of zinc acetate stimulated the activity of the enzym e in a dose-dependent manner when assayed at pH 10.5 (EC(50) = 20.3 +/ - 3.0 mu M), this did not result in a reciprocal inhibition of glycero phosphocholine phosphodiesterase (GPC PD) activity when assayed at a m ore acidic pH. This may suggest that human brain contains two phosphoc holine-producing GPC PD activities, differentiable by their sensitivit y to zinc ions. An activity capable of hydrolyzing GPE to form phospho ethanolamine could not be detected in either biopsied or autopsied bra in. However, a choline/ethanolamine-producing glycerophosphodiesterase activity could be readily detected in biopsied, but not autopsied bra in. This novel enzyme possessed a neutral pH optimum and was dependent upon divalent cations for activity. In conclusion, human brain contai ns at least two different glycerophosphodiesterases, a phosphocholine, and a choline/ethanolamine-producing activity, only one of which can be detected in autopsied tissue. The results of previous studies measu ring brain glycerophosphodiesterase activity in degenerative brain con ditions may need to be reevaluated in the light of these observations.