Inhibition of Urease Activity by Hydroxamic Acid Derivatives of Amino Acids

• Published in: Journal of biochemistry (Tokyo) 1975-04, Vol.77 (4), p.837-843
• Main Authors: KOBASHI, Kyoichi, TAKEBE, Sachiko, TERASHIMA, Nobuo, HASE, Jun'ichi
• Format: Article
• Language: English
• Subjects: Amino Acids - pharmacology; Animals; Asparaginase - antagonists & inhibitors; Asparaginase - metabolism; Binding, Competitive; Cecum - enzymology; Centrifugation; Female; Hydrogen-Ion Concentration; Hydroxamic Acids - pharmacology; Ileum - enzymology; Plants - enzymology; Rats; Structure-Activity Relationship; Urease - antagonists & inhibitors
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a130791

Hydroxamic acids have been reported to be potent and specific inhibitors of urease [EC 3.5.1.5] activity of plant and bacterial origin. The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats. Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9×10−6M) among nineteen α-aminoacyl hydroxamic acids. Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power. The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition. The I50 values of α-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids. This fact shows that the α-amino group did not affect inhibitory power. However, aspartic-β-, lysine-, and glutamic-γ-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or ω-amino group. Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to higher pH in the presence of an amino group. The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid. Hydroxamic acid inhibits urease actitity with strict specificity, except for aspartic-β-hydroxamic acid, which inhibited asparaginase competitively. Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine.