2-Fluoro-beta-alanine, a previously unrecognized substrate for bile acid coenzyme A:amino acid:N-acyltransferase from human liver

Biochemical Pharmacology
M R JohnsonR B Diasio

Abstract

Our laboratory has demonstrated recently that conjugates of 2-fluoro-beta-alanine (FBAL) and bile acids are the major biliary metabolites of 5-fluorouracil (FUra) in cancer patients. Bile acids are normally conjugated with glycine or taurine, and therefore the identification of the FBAL-bile acid conjugates suggested that FBAL may also be a substrate for the bile acid conjugating enzyme, bile acid CoA:amino acid:N-acyltransferase. Enzyme activity detected using glycine and taurine as substrates was purified 8-fold from human liver cytosol using a DEAE-cellulose column. This preparation when tested for its activity towards beta-alanine and FBAL using cholyl CoA as the bile acid substrate only catalyzed the formation of FBAL-cholate. beta-Alanine was not a substrate. Confirmation of FBAL-cholate as the enzymatic product was demonstrated by (1) coelution of the product of this reaction on HPLC with authentic FBAL-cholate, (2) specific hydrolysis of this product by cholylglycine hydrolase, and (3) molecular weight of the product (497) being identical to that of the authentic FBAL-cholate. Kinetic experiments demonstrated that the enzyme had an affinity for FBAL (Km 1.45 mM) comparable to taurine (Km 1.32 mM), but greater than glyci...Continue Reading

References

Jan 1, 1979·Methods in Enzymology·W W Cleland
Apr 1, 1989·Clinical Pharmacokinetics·R B Diasio, B E Harris
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·D J SweenyR B Diasio
Nov 1, 1968·Steroids·P P Shah, E Staple
Oct 11, 1963·Science·L PERIC-GOLIA, R S JONES

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Citations

Jan 1, 1991·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·J B KwakyeR B Diasio
Mar 24, 2016·Gut Microbes·Jason M RidlonH Rex Gaskins
May 28, 2016·Journal of Lipid Research·Nathan A StylesCharles N Falany

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