Sakae Mukaino

Proceedings of the 19th autumn meeting from October 18 to 20, 1977-Nara, Japan

The first step in the formation of bile acids is 7uhydroxylation of cholesterol. Subsequently 7ahydroxycholest-4-en-3-one is formed, which is a common precursor of the two primary bile acids, cholic acid and chenodeoxycholic acid. 5,BCholestane-3~t , 7a -d io l , a p recursor of chenodeoxycholic acid is formed from the A4-3-keto intermediate by a pathway which involves the reduction of the keto group and the saturation of the double bond but not a hydroxylation at C-12, while a pathway involving the 12a-hydroxylation of the A4-3-keto intermediate leads to the formation of 5flcholestane-3~, 7a, 12a-triol, which is a precursor of cholic acid. The C2~-bile alcohol intermediates , 5flcholestane-3a, 7t~-diol and 5,g-cholestane-3tz, 7t~, 1 2 ~ t r i o l , a r e t h e n t r a n s f o r m e d i n t o chenodeoxycholic acid and cholic acid by the degradation of the side chain which entails an moxidation followed by fl-oxidation. Chenodeoxycholic acid is also formed by a number of different pathways differing only with respect to the stage of nuclear transformation at which oxidation of the side chain is initiated. A number of cholestanepolyols such as 5flcholestane-3ct, 70t, 12ct, 25-tetrol are accumulated in the bile and feces of patients with cerebrotendinous xanthomatosis. No 26-hydroxylated bile alcohols are accumulated. The results suggest that there exists an alternative pathway of cholic acid biosynthesis involving the 25-hydroxylated bile alcohol as an intermediate. (2) Analytical methods of bile acids in biological materials