urchin Strongylocentrotus purpuratus, although
only in the terminal regions (amino acids 1-340
and 537-932); the linker region shows hardly any
similarity to the mammalian enzyme. The human
and yeast enzymes have about 50 % amino acids in
common [4, 20, 129]. In the mammals, the highest
activities are found in the liver and gut, with significantly less in all other tissues. The enzyme
activity shows a marked diurnal rhythm with a
maximum during the night, and the enzyme can be
inactivated by phosphorylation. The proportion of
the active non-phosphorylated form, which in rat
liver is normally about 10-20 %, is increased by
insulin or glucagon and reduced by the supply of
cholesterol. Synthesis of the enzyme also responds
to feeding of cholesterol [25]. The condensation of
the isoprenoid components is catalysed by several
different enzymes, at least in the mammals, and
different end products are produced, e.g. dolichol
or the side-chain of ubiquinone. The only enzyme
to have been isolated, the 80-kDa enzyme which
produces farnesyl pyrophosphate, was obtained
from the liver of the chicken and several mammals. Condensation of two molecules of farnesyl
pyrophosphate gives rise initially to pre-squalene
pyrophosphate, which by cleavage of the pyrophosphate and reduction by NADPH is converted
to squalene. These two reaction steps may be catalysed by the same microsomal enzyme. Squalene
epoxidase, squalene cyclase and the enzymes of
the further reaction steps from lanosterol to cholesterol are bound to the membrane of the endoplasmic reticulum [25].
16.2 Sterols of Different Animal Groups
Cholesterol is the predominant sterol of the vertebrates, tunicates, annelids, arthropods and molluscs, but in most cases other sterols are also present. Marine animals, such as the Porifera, Cnidaria and echinoderms, always contain an extraordinarily large variety of sterols. Of the numerous sterols that can be identified in individuals of
these animal groups by use of present-day refined
analytical techniques, most occur only in amounts
of one or a few percent. Marine invertebrates typically possess 10-30 types of sterols; no fewer
than 74 different sterols were identified in the
sponge Axinella cannabina [51]. The marine sterols are indeed a particularly stimulating research
field for biochemists! Amongst the marine sterols
are many which are not found in terrestrial organisms. For example, many plant sterols have alkyl
16.2 Sterols of Different Animal Groups
627
substituents on C-24, whereas C-22 and C-23 substitutions are only found in marine organisms.
Sterols with cyclopropane-substituted sidechains, with reduced A rings (A-norsterols) or
without the 19-methyl group (19-norsterols), and
polyhydroxy sterols or epidioxy sterols occur only
amongst the marine sterols (Fig. 16.9). Given that
many other animals, including the mammals,
survive with only cholesterol as the predominant
sterol component of their cell membranes, the
variety of sterols in the marine invertebrates is
probably not required to satisfy specific needs as
. the result of adaptive evolutionary processes. It
appears much more likely, as in the case of the
fatty acids, that nature is "experimenting" with
different structural variants in these primitive
organisms and will "chose" the most suitable. The
predominance in most animals of cholesterol,
which is the starting point for the biosynthesis of
the other sterols, is quite compatible with this
concept. The presence of a particular sterol in an
organism may be the result of de novo synthesis
via cholesterol or of uptake in the diet and eventual metabolic modification; it may also be a
product of symbiontic algae, fungi or bacteria
[37]. Numerous tracer experiments with acetate
or mevalonate have been carried out to determine which animals are capable of de novo cholesterol synthesis; unfortunately, the results are in
some cases ambiguous. Whilst the sterol components in the diet of terrestrial animals are in general easy to define, the availability of sterols in
the diet of marine animals is almost impossible to
estimate [37].
Apparently all, or almost all, animals can synthesize isoprenoid components and polyisoprenoids such as dolichol or the side-chains of ubiquinone or menaquinone (vitamin K group);
however, many appear unable to produce cholesterol and very often also squalene. The ability to
synthesize cholesterol has been clearly demonstrated in vertebrates, tunicates, annelids, nemertines and echinoderms. It is also quite certain that
the arthropods lack this capacity. Among the molluscs, the gastropods and amphineurans have
been shown to carry out limited cholesterol biosynthesis, whereas for the bivalves and cephalopods there are more negative than positive
results. The Porifera and Cnidaria appear unable
to synthesize any sterols, although the situation is
not yet completely clear; in this case, it is difficult
to exclude fully the participation of the everpresent symbionts [37, 56].
Probably by means of absorption, catabolic,
and excretory processes, all animals are in a posi-
only in the terminal regions (amino acids 1-340
and 537-932); the linker region shows hardly any
similarity to the mammalian enzyme. The human
and yeast enzymes have about 50 % amino acids in
common [4, 20, 129]. In the mammals, the highest
activities are found in the liver and gut, with significantly less in all other tissues. The enzyme
activity shows a marked diurnal rhythm with a
maximum during the night, and the enzyme can be
inactivated by phosphorylation. The proportion of
the active non-phosphorylated form, which in rat
liver is normally about 10-20 %, is increased by
insulin or glucagon and reduced by the supply of
cholesterol. Synthesis of the enzyme also responds
to feeding of cholesterol [25]. The condensation of
the isoprenoid components is catalysed by several
different enzymes, at least in the mammals, and
different end products are produced, e.g. dolichol
or the side-chain of ubiquinone. The only enzyme
to have been isolated, the 80-kDa enzyme which
produces farnesyl pyrophosphate, was obtained
from the liver of the chicken and several mammals. Condensation of two molecules of farnesyl
pyrophosphate gives rise initially to pre-squalene
pyrophosphate, which by cleavage of the pyrophosphate and reduction by NADPH is converted
to squalene. These two reaction steps may be catalysed by the same microsomal enzyme. Squalene
epoxidase, squalene cyclase and the enzymes of
the further reaction steps from lanosterol to cholesterol are bound to the membrane of the endoplasmic reticulum [25].
16.2 Sterols of Different Animal Groups
Cholesterol is the predominant sterol of the vertebrates, tunicates, annelids, arthropods and molluscs, but in most cases other sterols are also present. Marine animals, such as the Porifera, Cnidaria and echinoderms, always contain an extraordinarily large variety of sterols. Of the numerous sterols that can be identified in individuals of
these animal groups by use of present-day refined
analytical techniques, most occur only in amounts
of one or a few percent. Marine invertebrates typically possess 10-30 types of sterols; no fewer
than 74 different sterols were identified in the
sponge Axinella cannabina [51]. The marine sterols are indeed a particularly stimulating research
field for biochemists! Amongst the marine sterols
are many which are not found in terrestrial organisms. For example, many plant sterols have alkyl
16.2 Sterols of Different Animal Groups
627
substituents on C-24, whereas C-22 and C-23 substitutions are only found in marine organisms.
Sterols with cyclopropane-substituted sidechains, with reduced A rings (A-norsterols) or
without the 19-methyl group (19-norsterols), and
polyhydroxy sterols or epidioxy sterols occur only
amongst the marine sterols (Fig. 16.9). Given that
many other animals, including the mammals,
survive with only cholesterol as the predominant
sterol component of their cell membranes, the
variety of sterols in the marine invertebrates is
probably not required to satisfy specific needs as
. the result of adaptive evolutionary processes. It
appears much more likely, as in the case of the
fatty acids, that nature is "experimenting" with
different structural variants in these primitive
organisms and will "chose" the most suitable. The
predominance in most animals of cholesterol,
which is the starting point for the biosynthesis of
the other sterols, is quite compatible with this
concept. The presence of a particular sterol in an
organism may be the result of de novo synthesis
via cholesterol or of uptake in the diet and eventual metabolic modification; it may also be a
product of symbiontic algae, fungi or bacteria
[37]. Numerous tracer experiments with acetate
or mevalonate have been carried out to determine which animals are capable of de novo cholesterol synthesis; unfortunately, the results are in
some cases ambiguous. Whilst the sterol components in the diet of terrestrial animals are in general easy to define, the availability of sterols in
the diet of marine animals is almost impossible to
estimate [37].
Apparently all, or almost all, animals can synthesize isoprenoid components and polyisoprenoids such as dolichol or the side-chains of ubiquinone or menaquinone (vitamin K group);
however, many appear unable to produce cholesterol and very often also squalene. The ability to
synthesize cholesterol has been clearly demonstrated in vertebrates, tunicates, annelids, nemertines and echinoderms. It is also quite certain that
the arthropods lack this capacity. Among the molluscs, the gastropods and amphineurans have
been shown to carry out limited cholesterol biosynthesis, whereas for the bivalves and cephalopods there are more negative than positive
results. The Porifera and Cnidaria appear unable
to synthesize any sterols, although the situation is
not yet completely clear; in this case, it is difficult
to exclude fully the participation of the everpresent symbionts [37, 56].
Probably by means of absorption, catabolic,
and excretory processes, all animals are in a posi-