出版社：American Society for Biochemistry and Molecular Biology
摘要：Secondary bile acids, produced solely by intestinal bacteria,can accumulate to high levels in the enterohepatic circulationof some individuals and may contribute to the pathogenesis ofcolon cancer, gallstones, and other gastrointestinal (GI) diseases.Bile salt hydrolysis and hydroxy group dehydrogenation reactionsare carried out by a broad spectrum of intestinal anaerobicbacteria, whereas bile acid 7-dehydroxylation appears restrictedto a limited number of intestinal anaerobes representing a smallfraction of the total colonic flora. Microbial enzymes modifyingbile salts differ between species with respect to pH optima,enzyme kinetics, substrate specificity, cellular location, andpossibly physiological function. Crystallization, site-directedmutagenesis, and comparisons of protein secondary structurehave provided insight into the mechanisms of several bile acid-biotransformingenzymatic reactions. Molecular cloning of genes encoding bilesalt-modifying enzymes has facilitated the understanding ofthe genetic organization of these pathways and is a means ofdeveloping probes for the detection of bile salt-modifying bacteria.The potential exists for altering the bile acid pool by targetingkey enzymes in the 7/ß-dehydroxylation pathway throughthe development of pharmaceuticals or sequestering bile acidsbiologically in probiotic bacteria, which may result in theireffective removal from the host after excretion.Supplementary key words bile acids • deoxycholic acid • 7-dehydroxylation • gallstone disease • colon cancer • bile salt hydrolase • probiotics • hydroxysteroid dehydrogenase • hydrogen sulfide
Abbreviations:bai, bile acid-inducible; BSH, bile salt hydrolase; CA, cholic acid; CBAH-1, conjugated bile acid hydrolase from C. perfringens; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; GDCA, glycodeoxycholate; HSDH, hydroxysteroid dehydrogenase; LCA, lithocholic acid; TDCA, taurodeoxycholate; UDCA, ursodeoxycholic acid
/ß-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.
Supplementary key words bile acids • deoxycholic acid • 7
