628
16 Sterols and Steroids
tion to select particular sterols from those available in the diet and introduce them into the sterol
spectrum of their tissues. It also appears that all
animals, including those unable to synthesize sterols de novo, can metabolically modify those sterols taken up in the diet. Very common, though
not universal, is the removal of the alkyl substituents on C-24 (24-dealkylation) and the reduction
or creation of double bonds. Many sterols can be
autoxidized, and the accumulation of autoxidation products is common in marine invertebrates,
where storage of excretory products is more usual
than in terrestrial animals. Sterol esters can be
produced by acyl transfer to the 3~-OH group
present in almost all sterols, and cleaved again by
specific hydrolases. These are storage and transport forms of sterols and are more usual in intracellular fat droplets than in membranes. Sulphate
esters are also found at low levels in probably all
animals; only in the case of the echinoderms are
most of the sterols sulphated. Sterol glycosides
and sulphated steroid saponins are also more-orless restricted to this phylum. However, various
sterol conjugates may be formed by detoxification
processes prior to excretion.
16.2.1 Sterols of the Vertebrates
The terrestrial vertebrates have almost exclusively cholesterol; up to one-third of the total sterols in marine fish may be made up of other sterols that are quite clearly derived from sterols in
the diet. Marine teleosts also have bioactive steroid glycosides, e.g. the six different "pavoninins"
of Pardachirus marmoratus; these are steroids
with O-~-glycosidic-bound N-acetylglucosamine
that have a deterrent effect on sharks [115].
The human cholesterol requirement is usually
covered in equal proportions by the diet and by
de novo synthesis, which mainly occurs in the
liver. The cholesterol absorbed from the gut
lumen with the lipid micelles is incorporated by
the gut cells into chylomicrons which enter the
lymph and, therefore, eventually the blood circulation. As a result of the exchange and conversion processes between the different types of
plasma lipoproteins, the then esterified cholesterol is mostly found in the blood bound to LDL
(low-density lipoproteins). The esterification of
cholesterol in the circulatory system takes place
on HDL (high-density lipoproteins) by the action
of the plasma enzyme lecithin : cholesterol acyltransferase. Similar enzymes have been found in
the blood plasma of the trout Salmo alpinus and
in frog blood. The cholesterol transported in the
blood provides the starting material for the biosynthesis of steroid hormones in the gonads and
the adrenal cortex. The most important degradation products of cholesterol are the bile salts;
about 1 g cholesterol is used daily in the synthesis
of bile salts in the human liver. Because of the
limited water solubility of cholesterol and its precursors, they must be bound to carrier proteins
for metabolism and transport processes in the
liver cells. The squalene-binding protein of rat
liver (SCP-1) is essential for the biosynthetic
pathway from squalene to lanosterol, and the
sterol-binding protein (SCP-2) is required for the
pathway from lanosterol to cholesterol and for
intracellular cholesterol transport. Together with
for example, the "Z protein" and the fatty acidbinding proteins, these two proteins belong to a
family of closely related 12- to 16-kDa proteins,
representatives of which are found not only in
other rat tissues but also in shark and trout liver
[5]. A subsection of the 122-amino-acid sequence
of SCP-2 from rat liver shows significant homology to the variable domain of the heavy immunoglobulin chain [90].
16.2.2 Sterols of the Insects
Insects, like all other arthropods, are unable to
synthesize cholesterol or squalene de novo, and
require sterols as essential nutrients. The symbiontic microorganisms present in almost all insects
participate to a high degree in the satisfaction of
the host's sterol requirements, and some insect
species require no further supply of exogenous
sterols. Cholesterol is, in most cases, the optimal
source, although Drosophila pachea and Xyleborus ferrugineus are reported to require L\7-sterols.
According to the results of many feeding experiments, sterol requirements can almost always be
met by many different sterols, although the
demands of individual species can differ markedly [112]. Herbivorous insects in particular have
a versatile capacity for converting plant ~8 and
C29 sterols into cholesterol, i.e. for removing the
alkyl substituent on C-24. Other insects, e.g. the
hide beetle Dermestes maculatus, the housefly
Musca domestica and certain predatory Hemiptera, lack the capacity for 24-dealkylation. The
silkworm Bombyx mori requires sterols with the
cholestan side-chain; however, these can be variously ring desaturated. Sterols in the insects function as membrane components and as precursors
of the moulting hormones, and these different
16 Sterols and Steroids
tion to select particular sterols from those available in the diet and introduce them into the sterol
spectrum of their tissues. It also appears that all
animals, including those unable to synthesize sterols de novo, can metabolically modify those sterols taken up in the diet. Very common, though
not universal, is the removal of the alkyl substituents on C-24 (24-dealkylation) and the reduction
or creation of double bonds. Many sterols can be
autoxidized, and the accumulation of autoxidation products is common in marine invertebrates,
where storage of excretory products is more usual
than in terrestrial animals. Sterol esters can be
produced by acyl transfer to the 3~-OH group
present in almost all sterols, and cleaved again by
specific hydrolases. These are storage and transport forms of sterols and are more usual in intracellular fat droplets than in membranes. Sulphate
esters are also found at low levels in probably all
animals; only in the case of the echinoderms are
most of the sterols sulphated. Sterol glycosides
and sulphated steroid saponins are also more-orless restricted to this phylum. However, various
sterol conjugates may be formed by detoxification
processes prior to excretion.
16.2.1 Sterols of the Vertebrates
The terrestrial vertebrates have almost exclusively cholesterol; up to one-third of the total sterols in marine fish may be made up of other sterols that are quite clearly derived from sterols in
the diet. Marine teleosts also have bioactive steroid glycosides, e.g. the six different "pavoninins"
of Pardachirus marmoratus; these are steroids
with O-~-glycosidic-bound N-acetylglucosamine
that have a deterrent effect on sharks [115].
The human cholesterol requirement is usually
covered in equal proportions by the diet and by
de novo synthesis, which mainly occurs in the
liver. The cholesterol absorbed from the gut
lumen with the lipid micelles is incorporated by
the gut cells into chylomicrons which enter the
lymph and, therefore, eventually the blood circulation. As a result of the exchange and conversion processes between the different types of
plasma lipoproteins, the then esterified cholesterol is mostly found in the blood bound to LDL
(low-density lipoproteins). The esterification of
cholesterol in the circulatory system takes place
on HDL (high-density lipoproteins) by the action
of the plasma enzyme lecithin : cholesterol acyltransferase. Similar enzymes have been found in
the blood plasma of the trout Salmo alpinus and
in frog blood. The cholesterol transported in the
blood provides the starting material for the biosynthesis of steroid hormones in the gonads and
the adrenal cortex. The most important degradation products of cholesterol are the bile salts;
about 1 g cholesterol is used daily in the synthesis
of bile salts in the human liver. Because of the
limited water solubility of cholesterol and its precursors, they must be bound to carrier proteins
for metabolism and transport processes in the
liver cells. The squalene-binding protein of rat
liver (SCP-1) is essential for the biosynthetic
pathway from squalene to lanosterol, and the
sterol-binding protein (SCP-2) is required for the
pathway from lanosterol to cholesterol and for
intracellular cholesterol transport. Together with
for example, the "Z protein" and the fatty acidbinding proteins, these two proteins belong to a
family of closely related 12- to 16-kDa proteins,
representatives of which are found not only in
other rat tissues but also in shark and trout liver
[5]. A subsection of the 122-amino-acid sequence
of SCP-2 from rat liver shows significant homology to the variable domain of the heavy immunoglobulin chain [90].
16.2.2 Sterols of the Insects
Insects, like all other arthropods, are unable to
synthesize cholesterol or squalene de novo, and
require sterols as essential nutrients. The symbiontic microorganisms present in almost all insects
participate to a high degree in the satisfaction of
the host's sterol requirements, and some insect
species require no further supply of exogenous
sterols. Cholesterol is, in most cases, the optimal
source, although Drosophila pachea and Xyleborus ferrugineus are reported to require L\7-sterols.
According to the results of many feeding experiments, sterol requirements can almost always be
met by many different sterols, although the
demands of individual species can differ markedly [112]. Herbivorous insects in particular have
a versatile capacity for converting plant ~8 and
C29 sterols into cholesterol, i.e. for removing the
alkyl substituent on C-24. Other insects, e.g. the
hide beetle Dermestes maculatus, the housefly
Musca domestica and certain predatory Hemiptera, lack the capacity for 24-dealkylation. The
silkworm Bombyx mori requires sterols with the
cholestan side-chain; however, these can be variously ring desaturated. Sterols in the insects function as membrane components and as precursors
of the moulting hormones, and these different