FISH NUTRITION
445
present in prokaryotes (Rothfield and Finkelstein, 1968). The bulk
of cholesterol in animals is found associated with membrane systems.
Second, cholesterol is the direct precursor of bile salts and bile acids
that are produced in the liver and are essential in fat absorption as
well as excretion of cholesterol itself. Third, cholesterol is an important
precursor of the steroid hormones, including the androgens, the
oestrogens and the corticosteroids. This last role is extremely important,
although only small quantities of cholesterol are involved.
In mammals it is known that virtually all tissues are capable of
synthesizing cholesterol though, quantitatively, the most important
tissues are the intestine, the liver and the skin (Srere et al., 1950;
Dietschy and Siperstein, 1967). The pathway for cholesterol biosynthesis is very well understood apart from detailed steps and may be
summarized thus :
acetyl coenzyme A + mevalonic acid -+ squalene --f
squalene oxide --f lanosterol -+ cholesterol.
In mammals this pathway is controlled very largely at the stage where
acetyl coenzyme A is converted to mevalonic acid, though subsidiary
controls may also exist between mevalonic acid and squalene and
between squalene and squalene oxide (Siperstein and Guest, 1959 ;
Bucher et al., 1960 ; Siperstein and Fagan, 1966 ; Dorsey and Porter,
1968 ; Siperstein and Luby, 1969). Important studies with the rainbow
trout have also confirmed that, in this species, the major control point
in cholesterol biosynthesis in liver is between acetyl coenzyme A and
mevalonic acid (Siperstein and Luby, 1969). I n the latter work it was
shown that hepatomas, induced in trout liver by feeding the dietary
carcinogen aflatoxin (Halver, 1967), showed an unusually high rate of
cholesterol biosynthesis due to the fact that the normal feedback
inhibition exerted by cholesterol on the enzyme 8-hydroxyl-8-methylglutaryl coenzyme A reductase was abolished. In normal trout livers
the rate of biosynthesis of cholesterol was similar to that observed in
rat liver and the pathway was qualitatively the same. It is noteworthy
that trout contains adiposite muscle rather than adiposite liver so that
the latter organ in trout probably functions largely in a similar fashion
to mammalian liver.
The situation concerning the control of the overall levels of cholesterol in mammals is still not fully understood despite intensive
research in this area in relation to human arteriosclerosis. Factors
involved in cholesterol turnover in man have recently been reviewed
by Nestel (1970). It is known, however, that the final cholesterol levels
in tissues represent a balance between input of dietary cholesterol and
445
present in prokaryotes (Rothfield and Finkelstein, 1968). The bulk
of cholesterol in animals is found associated with membrane systems.
Second, cholesterol is the direct precursor of bile salts and bile acids
that are produced in the liver and are essential in fat absorption as
well as excretion of cholesterol itself. Third, cholesterol is an important
precursor of the steroid hormones, including the androgens, the
oestrogens and the corticosteroids. This last role is extremely important,
although only small quantities of cholesterol are involved.
In mammals it is known that virtually all tissues are capable of
synthesizing cholesterol though, quantitatively, the most important
tissues are the intestine, the liver and the skin (Srere et al., 1950;
Dietschy and Siperstein, 1967). The pathway for cholesterol biosynthesis is very well understood apart from detailed steps and may be
summarized thus :
acetyl coenzyme A + mevalonic acid -+ squalene --f
squalene oxide --f lanosterol -+ cholesterol.
In mammals this pathway is controlled very largely at the stage where
acetyl coenzyme A is converted to mevalonic acid, though subsidiary
controls may also exist between mevalonic acid and squalene and
between squalene and squalene oxide (Siperstein and Guest, 1959 ;
Bucher et al., 1960 ; Siperstein and Fagan, 1966 ; Dorsey and Porter,
1968 ; Siperstein and Luby, 1969). Important studies with the rainbow
trout have also confirmed that, in this species, the major control point
in cholesterol biosynthesis in liver is between acetyl coenzyme A and
mevalonic acid (Siperstein and Luby, 1969). I n the latter work it was
shown that hepatomas, induced in trout liver by feeding the dietary
carcinogen aflatoxin (Halver, 1967), showed an unusually high rate of
cholesterol biosynthesis due to the fact that the normal feedback
inhibition exerted by cholesterol on the enzyme 8-hydroxyl-8-methylglutaryl coenzyme A reductase was abolished. In normal trout livers
the rate of biosynthesis of cholesterol was similar to that observed in
rat liver and the pathway was qualitatively the same. It is noteworthy
that trout contains adiposite muscle rather than adiposite liver so that
the latter organ in trout probably functions largely in a similar fashion
to mammalian liver.
The situation concerning the control of the overall levels of cholesterol in mammals is still not fully understood despite intensive
research in this area in relation to human arteriosclerosis. Factors
involved in cholesterol turnover in man have recently been reviewed
by Nestel (1970). It is known, however, that the final cholesterol levels
in tissues represent a balance between input of dietary cholesterol and