Formation of Other Primary Bile Acids

Chenodeoxycholic acid is converted into a-muricholic acid (3a,6i8,7a-trihydroxy-5jS-cholanoic acid) and j8-muricholic acid (3a,6)J,7/J-trihydroxy-5j8-cholanoic acid) in the mouse and the rat and probably also in man (68, 102, Chapter 11 in this volume). a-Muricholic acid is a precursor of jS-muri-cholic acid in a reaction involving the intermediary formation of the 7-oxo compound (Chapter 11 in this volume). In the rat, /8-muricholic acid has been shown to be formed also from 3a,7j8-dihydroxy-5i8-cholanoic acid, which is a minor metabolite of chenodeoxycholic acid, and from 3a,6)9-dihydroxy-5)5-cholanoic acid, which is a metabolite of lithocholic acid (Chapter 11 in this volume). The microsomal 6i8-hydroxylase system in rat liver catalyzing the conversion of (tauro)chenodeoxycholic ac d into (tauro)a-muricholic acid has been studied by Hsia and collaborators (103-105), who 

Deoxycholic acid is predominantly if not exclusively a secondary bile acid formed from cholic acid (Chapter 11 in this volume). Deoxycholic acid has been shown to be formed from cholest-5-ene-3/3,12a-diol in ra(s and rabbits with a biliary fistula (53,54). However, only minute amounts of cholest-5-ene-3/ ,12a-diol are formed from cholesterol in the presence of the 20,000g supernatant fiuid of rat liver homogenate (55). Rosenfeld and Hell-man (109) have shown that 5/S-cholestan-3a-ol is converted efiiciently into deoxycholic acid in man, but there is at present no evidence that 5/ -cholestan-3a-ol is formed in the liver. 

In the guinea pig, 3a-hydroxy-7-oxo-5/9-cholanoic acid is partly a primary bile acid and partly a secondary bile acid formed from chenodeoxycholic acid (Chapter 11 in this volume) The pathway for the formation of 3a-hydroxy-7-oxo-5/9-cholanoic acid in the liver has not been established. It might be mentioned that 3/3-hydroxy-5-cholesten-7-one is not a precursor of this acid (110). 

Lithocholic acid, formed through the reactions described by Mitro-poulos and Myant (c/. Fig. 5 and Section III), is by definition a primary bile acid. Lithocholic acid is predominantly a secondary bile acid formed from chenodeoxycholic acid (Chapter 11 in this volume). Lithocholic acid is transformed by rat liver into 3a,6/S-dihydroxy-5/3-cholanoic acid, chenodeoxycholic acid, and a- and /S-muricholic acids (Chapter 11 in this volume). 

Allocholanoic acids (5a-cholanoic acids) are found mainly in lower animals (68,76), but small amounts of allocholic acid (3a,7a,12a-trihydroxy-5a-cholanoic acid), allodeoxycholic acid (3a,12a-dihydroxy-5a-cholanoic acid), and probably also allochenodeoxycholic acid (3a,7a-dihydroxy-5a-cholanoic acid) may be present in bile and feces of mammals (68,76,102). Karavolas et al. (Ill) and Ziller et al. (112) have shown that cholestanol is converted into allocholic acid and allochenodeoxycholic acid in rats with a biliary fistula. The conversion of cholestanol into allocholic acid has also been shown in the rabbit (113). Allodeoxycholic acid is a secondary bile acid, formed from allocholic acid (113,114) and deoxycholic acid (115,116). The early steps in the sequence of reactions from cholestanol to allocholic acid (Fig. 6) have been the subject of two recent investigations. Shefer et al. (17) have shown that the microsomal fraction of rat liver homogenate fortified with NADPH catalyzes 7a-hydroxylation of cholestanol. Bjorkhem and Gustafsson (117) have compared the rates of 7a-hydroxylation of cholestanol, 

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