Formation of urso- and ursodeoxy-cholic acids from primary bile acids by Clostridium absonum.
Eight strains of Clostridium absonum were shown to form ursocholic acid (UC) from cholic acid (C) and ursodeoxycholic acid (UDC) from chenodeoxycholic acid (CDC) but did not transform deoxycholic acid (DC) in whole cell cultures. The structures of UC and UDC were verified by mass spectroscopy, and by thin-layer chromatography using Komarowsky's spray reagent. The organism transformed C and CDC at concentrations below 1.5. 10(-3) M and 5.0. 10(-4) M, respectively; higher concentrations were inhibitory. Optimal yields of the final products were realized at about 15-22 hr and 9-15 hr of incubation, respectively, and were in the range of 60-70%. Additionally, the 7 keto-derivatives, 7 keto-deoxycholic acid (7K-DC) or 7 keto-lithocholic acid (7K-LC) were also formed from C and CDC. With longer periods of incubation, increasing yields of 7K-DC and 7K-LC and decreasing yields of UC and UDC were observed. These time course studies suggest that 7K-DC and 7K-LC are intermediates in the formation of UC and UDC from the primary bile acids. We propose the occurrence of C right harpoon over left harpoon 7K-DC right harpoon over left harpoon UC and CDC right harpoon over left harpoon 7K-LC right harpoon over left harpoon UDC with increasing dominance of back reaction of the second step on aging of the culture. When the initial pH value of the medium was manipulated within the range of 5.8-9.0, increasing yields of UDC from CDC were obtained at higher pH values (maximum yield at pH 9.0 was 83%), with total inhibition of growth and transformation at pH 5.8. In contrast, UC was produced from C at all pH values studied, with marginal differences in yields (maximum yield at pH 8.0 was 50%). In all cases, formation of UC from C was much slower than that of UDC from CDC. In contrast, C. paraperfringens transformed none of the above bile acids. We propose that C. absonum, or a biochemically similar species, may be present in the human gut and give rise to UDC (and UC) in vivo.-Macdonald, I. A., D. M. Hutchison, and T. P. Forrest. Formation of urso- and ursodeoxycholic acids from primary acids by Clostridium absonum.
D001647:Bile Acids and Salts / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002793:Cholic Acids / Q000378:metabolism*; D003013:Clostridium / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D007700:Kinetics; D013058:Mass Spectrometry; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D002793:Cholic Acids; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases; C030712:ursocholic acid