Irreversible inhibition of hexosaminidase C by medium-chain monocarboxylic acids and Triton X-100.
The neutral beta-N-acetylhexosaminidase (hexosaminidase C) from human brain was partially purified (separated from lysosomal beta-N-acetylhexosaminidases by chromatography on a Con A-Sepharose column). Hexosaminidase C was inhibited by medium-chain fatty acids (monocarboxylic acids with chain-length between C6 and C9), whereas shorter-chain monocarboxylic acids showed no inhibitory effect. Studies on the inhibition mechanism showed an irreversible and pH-dependent inhibition which progresses with time and which is not reversed by the removal of fatty acids (by Bio-Beads SM-2). Similar inhibitory effects were also obtained using Triton X-100 (but not with homologous alkylamines). These results suggest that the hexosaminidase C inactivation is related to the hydrophobic properties of the inhibitor which acts as a denaturing agent mainly at acidic pH. The possibility has been discussed that this inactivation effect of monocarboxylic acid on hexosaminidase C could constitute a molecular model of the toxicity of medium-chain-length fatty acids.
D001921:Brain / Q000201:enzymology; D002264:Carboxylic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D006596:Hexosaminidases / Q000037:antagonists & inhibitors*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology*
D002264:Carboxylic Acids; D005227:Fatty Acids; D007527:Isoenzymes; D011092:Polyethylene Glycols; D017830:Octoxynol; D006596:Hexosaminidases