Substrate specificity of cholylglycine hydrolase for the hydrolysis of bile acid conjugates.
The substrate specificity of cholylglycine hydrolase has been investigated using bile acid conjugates with modifications in the steroid ring system, the side chain, or the amino acid moiety. Epimerization at C-3 and C-7 did not affect the activity of the enzyme while oxidation of the three nuclear hydroxyl groups reduced the affinity of the enzyme toward the substrate. Elongation of the side chain by one or three carbons inhibited enzyme activity. Conjugates prepared from C24 bile acids and analogs of taurine and glycine with one or two methylene groups were effectively hydrolyzed, whereas conjugates with a tertiary amide group completely resisted hydrolysis. Increasing the length of the bile acid side chain or using a bile acid conjugate with a tertiary amide group may produce compounds that will resist intestinal bacterial destruction.
D000581:Amidohydrolases / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D003016:Clostridium perfringens / Q000201:enzymology; D005998:Glycine; D006000:Glycocholic Acid / Q000378:metabolism*; D006868:Hydrolysis; D007202:Indicators and Reagents; D007700:Kinetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013654:Taurine
D001647:Bile Acids and Salts; D007202:Indicators and Reagents; D013654:Taurine; D000581:Amidohydrolases; C023154:choloylglycine hydrolase; D006000:Glycocholic Acid; D005998:Glycine