The inhibitor-sensitive sites of galactosyl ceramide galactosidase

作者: Ramesh C. Arora , Yuh-Nan Lin , Norman S. Radin

DOI: 10.1016/0003-9861(73)90343-3

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摘要: A preparation of galactosyl ceramide galactosidase from rat brain has been tested with potential inhibitors which resemble the enzyme’s substrate. The amide made 2-hydroxydodecanoic acid and nL-erythro-3-phenyl-2-amino-1,3-propanediol proved to be a fine inhibitor, acting noncompetitively. Removal any three hydroxyl groups reduced effectiveness, as did inversion C-3 carbon atom or addition substituents on benzene ring. iV-Acetyl psychosine was an effective inhibitor mixed type while longer homolog, N-decanoyl psychosine, competitive well substrate for enzyme. Lactosyl ceramide, naturally occurring lipid, modest efficacy. Galactonola&one excellent I\r-(n-hexyl) R-as active type. It would appear above comparisons that site binds only galactose-containing galactose-resembling substances. secondary effector variety substances possess central nitrogenous core region cerebroside. As part attempt develop specific agents could block single steps in myelin metabolism, we have synthesized compounds structure component, (“cerebroside”). hydrolase normally acts this P-galactosidase, is defective human genetic disorder, Krabbe’s disease, enzyme might allow us generate model disorder rats mimics

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