Bile acid transformations by Alcaligenes recti.
Metabolism of cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid by the grown cells of the bacterium Alcaligenes recti suspended in water was studied. Each isolated metabolite was characterized by the application of various spectroscopic methods. Cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid yielded methylated derivatives 3 alpha-methoxy-7 alpha, 12 alpha-dihydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 alpha-hydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 beta-hydroxy-5 beta-cholanoic acid, and 3 alpha-methoxy-12 alpha-hydroxy-5 beta-cholanoic acid, respectively. In addition, cholic acid furnished 7 alpha, 12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid; chenodeoxycholic acid gave 7 alpha-hydroxy-3-oxo-5 beta-cholanoic acid and 7 alpha-hydroxy-3-oxochol-4-en-24-oic acid while ursodeoxycholic acid yielded 7 beta-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid. The formation of various metabolites showed that two competitive enzymic reactions, i.e., selective methylation of the 3 alpha-hydroxy group and dehydrogenation in the A/B rings, were operative. The methylation process was found to be enzymic involving an S-adenosyl-L-methionine (AdoMet)-dependent methyl transferase, and this reaction appeared to be inhibitory to the process of degradation of the ring system. In the other reaction sequence, degradation of the ring system was initiated by dehydrogenation of the 3 alpha-hydroxy group. A 7 beta-dehydratase activity producing the delta 6 double bond was also noticeable in the metabolism of ursodeoxycholic acid.
Mazumder
I
I
Indian Institute of Chemical Biology, Calcutta.
Mahato
S B
SB
D000421:Alcaligenes / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D015394:Molecular Structure; D012436:S-Adenosylmethionine / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014580:Ursodeoxycholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D012436:S-Adenosylmethionine; D008780:Methyltransferases; D019826:Cholic Acid