Cholylhydroxamic acid

The conjugation of bile acids with added hydroxylamine by rat liver microsomes in the presence of ATP, CoA, and fluoride to yield bile acid hydroxamates has been used to demonstrate the formation of cholyl-CoA as an intermediate in the enzymatic system catalyzing the synthesis of the natural conjugates (12,13). In pig liver, there appear to be two distinctly different enzyme systems capable of the synthesis of cholylhydroxamic acid (15). A partially solubilized preparation from pig liver catalyzed the rapid formation of cholylhydroxamic acid in the presence of cholic acid and hydroxylamine but in the absence of ATP and CoA. This is in contrast to the synthesis of hydroxamates of bile acids by the microsomes, which required both ATP and CoA. Since fluoride inhibits the system that functions in the absence of ATP and CoA, the reaction appears to be similar to that of a lipase (15)... 

Fig.2. Some synthetic iron chelators. Structures are numbered for reference in the text. Ill, deferiprone IV, MECAM V, DTPA VII, 2,3-DHB X, EHPG XI, cholylhydroxamic acid XII, HBED XIII, PIH...

Coenzyme A (CoA) derivatives of bile acids were prepared [33,34] by a modification of the mixed anhydride procedure for the synthesis of palmityl CoA. A yield of 70% was calculated from the quantity of cholylhydroxamate formed after treatment of the CoA derivative with hydroxylamine. By modification of this procedure and purification of the products by chromatography on Sephadex LH-20, aqueous solutions of CoA derivatives of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids were pbtained, frozen at - 70°C, and shown to be free from hydrolysis for several months [35]. 

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