3. LIPIDS: STEROID METABOLISM
187
(117). This results in the appearance of considerable quantities if conjugated deoxycholic acid in rabbit gall bladder bile, which might be
thought to have been formed in the liver. However, when a bile fistula
is established in the rabbit the deoxycholic acid disappears from the
fistula bile and is replaced by cholic acid. Investigations with animals
having bile fistulas have their own complications. When the enterohepatic circulation is thus interrupted and bile salts are not returned
to the liver, the rate of bile acid biosynthesis in the rat is greatly increased (106). This may be related to the fact that the rat is exceptional in not possessing a gall bladder. In bile-fistula dogs when the
collected bile is fed back to the dog the rate of excretion of bile salt is
greatly increased (118). In the intact dog much of the endogenous bile
acid may be transformed by intestinal bacteria to substances that cannot be reabsorbed.
5. Gallstone Formation
Gallstones consist in man almost entirely of cholesterol (119) and
occur very much more commonly in man than in other species. Their
formation may possibly be due to failure of man to adapt himself to a
relatively high cholesterol (flesh) diet (107). Other primates do not
have such a diet. Moreover, in man glycine conjugation of bile acids
occurs predominantly (120, 121) and the glycoconjugates may lack the
cholesterol-dissolving power of the tauroconjugates typical of the carnivore (dog) bile (119).
6. Bile Salts and Evolution
Haslewood (107) has suggested that investigation of bile salts may
be of value in the elucidation of the evolutionary history of different
species. Bile salts (regarded as "primitive") containing C 27 to C 29 bile
acids have been found in some teleostean and elasmobranch fishes,
amphibians, reptiles, and birds, but not in mammals. All animals found
so far to possess "primitive" bile salts show other primitive characteristics. Marine invertebrates and other lower animals possess sterols
having 28 or 29 carbon atoms, whereas the C 27 cholesterol is the characteristic sterol of higher animals. One might therefore reasonably expect to find in lower animals C 28 and C 29 bile alcohols and acids derived as shown in reaction sequence (1), where R is
# CH 3 or ·ΟΗ 2 ·ΟΗ 3 .
Such compounds may be unable to undergo oxidation at C-24, which,
occurring in the case of cholesterol (R = H), leads to the C 24 bile acids.
Hence in an evolutionary sense bile salt formation may be restricted to
C 28 or C 29 compounds in those animals which possess C 28 or C 29 sterols.
"Thus a vertebrate having bile salts of this kind may be said to have a
187
(117). This results in the appearance of considerable quantities if conjugated deoxycholic acid in rabbit gall bladder bile, which might be
thought to have been formed in the liver. However, when a bile fistula
is established in the rabbit the deoxycholic acid disappears from the
fistula bile and is replaced by cholic acid. Investigations with animals
having bile fistulas have their own complications. When the enterohepatic circulation is thus interrupted and bile salts are not returned
to the liver, the rate of bile acid biosynthesis in the rat is greatly increased (106). This may be related to the fact that the rat is exceptional in not possessing a gall bladder. In bile-fistula dogs when the
collected bile is fed back to the dog the rate of excretion of bile salt is
greatly increased (118). In the intact dog much of the endogenous bile
acid may be transformed by intestinal bacteria to substances that cannot be reabsorbed.
5. Gallstone Formation
Gallstones consist in man almost entirely of cholesterol (119) and
occur very much more commonly in man than in other species. Their
formation may possibly be due to failure of man to adapt himself to a
relatively high cholesterol (flesh) diet (107). Other primates do not
have such a diet. Moreover, in man glycine conjugation of bile acids
occurs predominantly (120, 121) and the glycoconjugates may lack the
cholesterol-dissolving power of the tauroconjugates typical of the carnivore (dog) bile (119).
6. Bile Salts and Evolution
Haslewood (107) has suggested that investigation of bile salts may
be of value in the elucidation of the evolutionary history of different
species. Bile salts (regarded as "primitive") containing C 27 to C 29 bile
acids have been found in some teleostean and elasmobranch fishes,
amphibians, reptiles, and birds, but not in mammals. All animals found
so far to possess "primitive" bile salts show other primitive characteristics. Marine invertebrates and other lower animals possess sterols
having 28 or 29 carbon atoms, whereas the C 27 cholesterol is the characteristic sterol of higher animals. One might therefore reasonably expect to find in lower animals C 28 and C 29 bile alcohols and acids derived as shown in reaction sequence (1), where R is
# CH 3 or ·ΟΗ 2 ·ΟΗ 3 .
Such compounds may be unable to undergo oxidation at C-24, which,
occurring in the case of cholesterol (R = H), leads to the C 24 bile acids.
Hence in an evolutionary sense bile salt formation may be restricted to
C 28 or C 29 compounds in those animals which possess C 28 or C 29 sterols.
"Thus a vertebrate having bile salts of this kind may be said to have a