FISH NUTRITION
447
cholesterol occurs ; when radioactive mevalonate is injected into
Scyliorhinus a similar picture emerges except that significant incorporation of mevalonic acid into bile sterols (bile salts and bile alcohol esters)
also occurs (Sargent et al., 1970). The latter findings probably imply
that Scyliorhinus has damped down the endogenous biosynthesis of
cholesterol in the liver due to the relatively high levels of cholesteryl
esters (2%) stored in the adiposite liver oil. Small amounts of additional
cholestertJ1 appearing in the liver are probably rapidly converted to bile
sterols. I n this way the animal can regulate the level of cholesterol in
its liver and may possibly also regulate the biosynthetic activity of the
intestine through the gut level of bile sterols. In these experiments
very little metabolism of acetate to squalene occurs, implying that the
pathway of cholesterol biosynthesis in Scyliorhinus liver is controlled
at the stages acetyl coenzyme A to mevalonate and squalene to
squalene oxide.
Similar experiments show that fractions of the liver of cod and plaice
do not have the ability to synthesize squalene from mevalonate
(Sargent and Towse, unpublished observations). These results again are
more likely to reflect damping down of endogenous cholesterol biosynthesis by adiposite liver cholesterol rather than a complete inability
of these species to synthesize cholesterol,
Differences do not occur between freshwater and salt-water fish
with respect to cholesterol biosynthesis ; the livers of freshwater and
marine bass both synthesized cholesterol at the same rate, although
this rate was much less than that present in rat livers (Blondin et al.,
1966). Cholesterol synthesis is as rapid in the livers of freshwater
rainbow trout as in the livers of salt-water rainbow trout (Sargent
and Towse, unpublished observations).
While considering cholesterol biosynthesis in fish it may be noteworthy that an important step in the pathway, viz. the oxidation of
squalene to squalene oxide prior to cyclization to lanosterol, involves
both NADPH" and molecular oxygen, i.e. a mixed function oxidase is
operating (Dean et al., 1967; Yamamoto and Bloch, 1970). Mixed
function oxidases utilizing NADPH and molecular oxygen are also
involved in demethylation steps between lanosterol and cholesterol.
It is now well established that such oxidases in general are located in
the endoplasmic reticulum of mammalian livers and are conventionally
isolated in the microsome fraction of liver homogenates (see e.g.
Siekevitz, 1963). Other important functions associated with these
electron transfer systems of microsomes are (1) detoxification of foreign
compounds (Remmer, 1964 ; Cooper et al., 1965), (2) lipid peroxidation,
* Reduoed niootinamide adenine dinuoleotide phosphate.
447
cholesterol occurs ; when radioactive mevalonate is injected into
Scyliorhinus a similar picture emerges except that significant incorporation of mevalonic acid into bile sterols (bile salts and bile alcohol esters)
also occurs (Sargent et al., 1970). The latter findings probably imply
that Scyliorhinus has damped down the endogenous biosynthesis of
cholesterol in the liver due to the relatively high levels of cholesteryl
esters (2%) stored in the adiposite liver oil. Small amounts of additional
cholestertJ1 appearing in the liver are probably rapidly converted to bile
sterols. I n this way the animal can regulate the level of cholesterol in
its liver and may possibly also regulate the biosynthetic activity of the
intestine through the gut level of bile sterols. In these experiments
very little metabolism of acetate to squalene occurs, implying that the
pathway of cholesterol biosynthesis in Scyliorhinus liver is controlled
at the stages acetyl coenzyme A to mevalonate and squalene to
squalene oxide.
Similar experiments show that fractions of the liver of cod and plaice
do not have the ability to synthesize squalene from mevalonate
(Sargent and Towse, unpublished observations). These results again are
more likely to reflect damping down of endogenous cholesterol biosynthesis by adiposite liver cholesterol rather than a complete inability
of these species to synthesize cholesterol,
Differences do not occur between freshwater and salt-water fish
with respect to cholesterol biosynthesis ; the livers of freshwater and
marine bass both synthesized cholesterol at the same rate, although
this rate was much less than that present in rat livers (Blondin et al.,
1966). Cholesterol synthesis is as rapid in the livers of freshwater
rainbow trout as in the livers of salt-water rainbow trout (Sargent
and Towse, unpublished observations).
While considering cholesterol biosynthesis in fish it may be noteworthy that an important step in the pathway, viz. the oxidation of
squalene to squalene oxide prior to cyclization to lanosterol, involves
both NADPH" and molecular oxygen, i.e. a mixed function oxidase is
operating (Dean et al., 1967; Yamamoto and Bloch, 1970). Mixed
function oxidases utilizing NADPH and molecular oxygen are also
involved in demethylation steps between lanosterol and cholesterol.
It is now well established that such oxidases in general are located in
the endoplasmic reticulum of mammalian livers and are conventionally
isolated in the microsome fraction of liver homogenates (see e.g.
Siekevitz, 1963). Other important functions associated with these
electron transfer systems of microsomes are (1) detoxification of foreign
compounds (Remmer, 1964 ; Cooper et al., 1965), (2) lipid peroxidation,
* Reduoed niootinamide adenine dinuoleotide phosphate.