Specific inhibition of human β-D-glucuronidase and α-L-iduronidase by a trihydroxy pipecolic acid of plant origin

• Published in: FEBS letters Vol. 176; no. 1; pp. 61 - 64
• Main Authors: di Bello, Isabelle Cenci, Dorling, Peter, Fellows, Linda, Winchester, Bryan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.10.1984; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Binding, Competitive; Biological and medical sciences; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glucuronidase - antagonists & inhibitors; Glycoside Hydrolases - antagonists & inhibitors; Humans; Hydrogen-Ion Concentration; Hydrolases; Iduronidase - antagonists & inhibitors; Liver - enzymology; Molecular Conformation; Novel glycosidase inhibitor; Pipecolic Acids - pharmacology; Seeds - analysis; Structure-Activity Relationship; Trihydroxypipecolic acid; α-L-lduronidase; β-D-Glucuronidase; α-L-lduronidase; Trihydroxypipecolic acid; Novel glycosidase inhibitor; β-D-Glucuronidase; Human; Stereoisomer; Β-D-Glucuronidase; L-Iduronidase; Enzyme; Liver; Inhibition
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(84)80911-4

The glucuronic acid analogue of 1-deoxynojirimycin, 2( S)-carboxy-3( R), 4( R), 5( S)-trihydroxypiperidine, recently isolated from seeds of Baphia racemosa, is a novel specific inhibitor of human liver β-D-glucuronidase and α-L-iduronidase. No other glycosidases are inhibited. The inhibition of β-D-glucuronidase is competitive, with a K i of 8 × 10 −5 M and is pH-dependent. This inhibitor may be useful to induce a mucopolysaccharidosis or to investigate the function of microsomal β-D-glucoronidase.