186
JAMES K. GRANT
HMabeled cholesterol injected into a dog is transformed into labeled
cholic acid and the quantitative importance of this pathway of cholesterol metabolism has been demonstrated in the rat (109). In man, however, isotope studies indicate that injected cholesterol is incorporated
more into fecal sterol than into the fecal bile acid fraction (110).
A tentative scheme for the biosynthesis of bile acids is shown in
Fig. 5. Hydroxylation of the cholesterol rings apparently must occur
before side-chain oxidation. An exception to this is the 7«-hydroxylation
of deoxycholic acid (XXXIII) which appears to be a reaction specific
for the rat—it does not occur in rabbit nor in man (111). Until recently
bile acid formation in the pig was regarded as unique among mammals
in so far as this species effected hydroxylation at the 6a-position. The
main bile acids of the pig include hyodeoxycholic acid (XXXVIII) and
hyocholic acid (XXXVII) (112). Bile acids with 6^-hydroxy substituents, however, have recently been isolated from rat bile (105).
3. Conjugation of Bile Acids
It has been shown (113) that the conjugation of bile acids involves
the intervention of coenzyme A, thus
Cholic acid + ATP + CoA -+ Cholyl CoA + AMP + PP
The enzyme system present in liver cell microsomes shows specificity
toward the amino acid involved. In presence of taurine and glycine
rabbit liver preparations give glycocholate only; chicken liver, taurocholate; and rat liver, both bile salts. Glycine conjugation has been observed only in mammalian species (112). Conjugated bile acids have
not been found in feces, bacteria of the large intestine being able to
effect hydrolysis (114).
4. Action of Intestinal Bacteria
The study of the formation of bile acids is complicated by the fact
that these substances are transformed by intestinal bacteria. Thus although cholic and chenodeoxycholic acids (XXXVI) account for over
90% of the bile acids in rat bile many more compounds appear in the
feces (106). One of the main transformations brought about by intestinal bacteria is removal of the hydroxyl at C-7 to give deoxycholic
acid. When germ-free rats (115) or animals given antibiotics (116)
are used, this reaction does not occur and the feces contain the same
bile salts as the bile. Deoxycholic acid thus formed in the rat may be
partially absorbed from the intestine and can undergo rehydroxylation
at the 7«-position in the liver. In the case of the rabbit, however,
deoxycholic acid formed by the intestinal bacteria is not rehydroxylated
JAMES K. GRANT
HMabeled cholesterol injected into a dog is transformed into labeled
cholic acid and the quantitative importance of this pathway of cholesterol metabolism has been demonstrated in the rat (109). In man, however, isotope studies indicate that injected cholesterol is incorporated
more into fecal sterol than into the fecal bile acid fraction (110).
A tentative scheme for the biosynthesis of bile acids is shown in
Fig. 5. Hydroxylation of the cholesterol rings apparently must occur
before side-chain oxidation. An exception to this is the 7«-hydroxylation
of deoxycholic acid (XXXIII) which appears to be a reaction specific
for the rat—it does not occur in rabbit nor in man (111). Until recently
bile acid formation in the pig was regarded as unique among mammals
in so far as this species effected hydroxylation at the 6a-position. The
main bile acids of the pig include hyodeoxycholic acid (XXXVIII) and
hyocholic acid (XXXVII) (112). Bile acids with 6^-hydroxy substituents, however, have recently been isolated from rat bile (105).
3. Conjugation of Bile Acids
It has been shown (113) that the conjugation of bile acids involves
the intervention of coenzyme A, thus
Cholic acid + ATP + CoA -+ Cholyl CoA + AMP + PP
The enzyme system present in liver cell microsomes shows specificity
toward the amino acid involved. In presence of taurine and glycine
rabbit liver preparations give glycocholate only; chicken liver, taurocholate; and rat liver, both bile salts. Glycine conjugation has been observed only in mammalian species (112). Conjugated bile acids have
not been found in feces, bacteria of the large intestine being able to
effect hydrolysis (114).
4. Action of Intestinal Bacteria
The study of the formation of bile acids is complicated by the fact
that these substances are transformed by intestinal bacteria. Thus although cholic and chenodeoxycholic acids (XXXVI) account for over
90% of the bile acids in rat bile many more compounds appear in the
feces (106). One of the main transformations brought about by intestinal bacteria is removal of the hydroxyl at C-7 to give deoxycholic
acid. When germ-free rats (115) or animals given antibiotics (116)
are used, this reaction does not occur and the feces contain the same
bile salts as the bile. Deoxycholic acid thus formed in the rat may be
partially absorbed from the intestine and can undergo rehydroxylation
at the 7«-position in the liver. In the case of the rabbit, however,
deoxycholic acid formed by the intestinal bacteria is not rehydroxylated