Sphingomyelinase activity at pH 7.4 in human brain and a comparison to activity at pH 5.0.
A hitherto undescribed sphingomyelinase (sph'ase 7.4) of human brain has been studied in crude and partially purified (3- to 4- fold) extracts of grey matter, and compared to the known sphingomyelinase with an acid pH optimum (sph'ase 5.0). Its specificity for sphingomyelin as substrate is similar to that of sph'ase 5.0, but it differs from sph'ase 5.0 in its pH optimum (7.4 vs 5.0) and in a requirement for Mg2+ for optimal activity. Other properties of sph'ase 7.4 that distinguish it from sph'ase 5.0 include (a) its lack of appreciable solubilization during dialysis of crude homogenates (b) a more marked concentrations in grey matter than in white matter (9- to 13- fold vs 1.5- to 2-fold for sph'ase 5.0); (c) inhibition by Ca2+ and Cd2+ ions, and by EDTA; (D) stimulation by dithiothreitol, and inhibition by cysteine, N-ethylmaleimide, and p-hydroxymercuribenzoate; (e) lack of inhibition by nucleotides (AMP.ADP, and ATP) and by NAD plus NADH; and (f) relative instability to storage or manipulation between -20degrees C and 40degrees C. These differences indicate the SPH'ASE 7.4 is a different enzyme protein from sph'ase 5.0. Unlike sph'ase 5.0, which is widely distributed in mammalian tissues, sph'ase 7.4 occurs predominantly in grey matter and little activity was observed is spleen, liver, or leukocytes. The high levels of this enzyme in brain suggest a role related to the specific functions of this organ or to the need for a more stringent control of sphingomyelin catabolism in brain as compared to other organs.
D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013696:Temperature
D013439:Sulfhydryl Reagents; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium; D002118:Calcium