Premium
Multiple forms of the enzyme glycerophosphodiesterase are present in human brain
Author(s) -
Ross Brian M.,
Sherwin Allan L.,
Kish Stephen J.
Publication year - 1995
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536607
Subject(s) - phosphocholine , enzyme , zinc , chemistry , biochemistry , phospholipid , human brain , choline , chromatography , phosphatidylcholine , biology , membrane , organic chemistry , neuroscience
Brain levels of glycerophosphodiesters, including glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), are altered in many human central nervous system disorders. Although much information is available on the enzymes responsible for the formation of these phospholipid metabolites, little information is known regarding their catabolism, by glycerophosphodiesterases, in human brain. In both autopsied and biopsied temporal cortex, a phosphocholine‐producing lycerophosphodiesterase 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 acetate shifted the pH optimum to 10.5. When assayed at pH 9.0 in the absence of zinc acetate, the K m and V max were 104±2 μM and 77±18 nmol/h/mg protein, respectively, while assaying at pH 10.5 in the presence of 5 mM zinc acetate yielded a K m of 964±56 μM, and a V max of 534±114 nmol/h/mg protein. Furthermore, whereas submillimolar concentrations of zinc acetate stimulated the activity of the enzyme in a dose‐dependent manner when assayed at pH 10.5 (EC 50 =20.3±3.0 μM), this did not result in a reciprocal inhibition of glycerophosphocholine phosphodiesterase (GPC PD) activity when assayed at a more acidic pH. This may suggest that human brain contains two phosphocholine‐producing GPC PD activities, differentiable by their sensitivity to zinc ions. An activity capable of hydrolyzing GPE to form phosphoethanolamine could not be detected in either biopsied or autopsied brain. However, a choline/ethanolamine‐producing glycerophosphodiesterase activity could be readily detected in biopsied, but not autopsied brain. This novel enzyme possessed a neutral pH optimum and was dependent upon divalent cations for activity. In conclusion, human brain contains 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 measuring brain glycerophosphodiesterase activity in degenerative brain conditions may need to be reevaluated in the light of these observations.