578
15 Lipids
boxylated to D-methylmalonyl-CoA, isomerized
to L-methylmalonyl-CoA, and then converted
by the cobalamin-dependent methylmalonyl-CoA
mutase to succinyl-CoA, which then enters the
citrate cycle. The same reactions but operating in
the opposite direction are used by some invertebrates to produce propionate from succinate in
anaerobic metabolism, so long as vitamin B12 is
available (p. 552). Various invertebrates are relatively rich in cobalamin and catabolize propionate, just as the vertebrates do. In contrast, all
insects, regardless of whether they have a lot of
vitamin B12 (e.g. the termite Zootermopsis nevadensis) , a little (e.g. the cockroach Periplaneta
americana) or none at all (e.g. the housefly
Musca domestica) , degrade propionate by the
same cobalamin-independent pathway: this involves the formation of 3-hydroxypropionate by
modified ~-oxidation and its decarboxylation to
acetate. In the process, the C-2 of the propionate
becomes the carboxyl group of acetate, and the
C-3 becomes the methyl group [81].
The existence of a B-oxidation system in peroxisomes was first discovered in the endosperm of
beans and in the ciliate Tetrahymena; it was later
found in the rat liver and other vertebrate tissues
and is probably also present in all invertebrates
[65]. The ~-oxidation of fatty acids in Tetrahymena is restricted entirely to the peroxisomes.
Although the reactions in the peroxisomes are the
same as those which occur in the mitochondria,
the enzymes are completely different. Whereas
the first mitochondrial enzyme is a dehydrogenase, which introduces electrons into the respiration chain and yields two ATPs, the first peroxisomal enzyme is an FAD-containing acyl-CoA oxidase which produces H20 2 and yields no ATP. The
peroxide is removed by the catalase in the peroxisomes. Because acyl-CoA oxidase is practically
inactive against acyl residues with fewer than ten
C atoms, the animal peroxisomes, in contrast to
plant microbodies, cannot completely catabolize
fatty acids [235]. Enoyl-CoA hydratase and 3hydroxylacyl-CoA dehydrogenase are combined
with ~3,~2-enoyl-CoA isomerase to give a trifunctional enzyme. In contrast to the homotetrameric enzyme of the mitochondria, the 3ketoacyl-CoA thiolase is a homodimer. How fatty
acids reach the peroxisomes is still not known.
Carnitine is not required; the carnitine acyltransferase in the peroxisomes is possibly involved in
the transport of short-chain fatty acids into the
mitochondria [235].
The concept that by shortening long-chain
fatty acids the peroxisomes prepare them for
complete degradation in the mitochondria apparently does not hold for all vertebrates. Certain
copepod species, which form the principal diet
of herring, mackerel and other pelagic fish, are
relatively rich in wax esters with the alcohol
22:1(n-11); this is oxidized to the corresponding
fatty acids in the gut mucosa. However, investigations of the rainbow trout Salma gairdneri show
that the fatty acids are not processed in the peroxisomes, the activity of which decreases with
increasing chain length from C12 to CIS. The mitochondria are in fact adapted to the particular fatty
acid composition of the diet in that they can oxidize a wide fatty acid spectrum of 12: 0 to 22: 6
[94].
The hydroxylation of lignoceric acid 24: 0 to
cerebronic acid 2-0H-24:0, an important constituent of brain glycolipids, occurs by the action
of a mixed-function oxygenase [195]. In the uropygial glands of many birds, fatty acids are
hydroxylated at C-2, C-3 or terminal C atoms
and are then metabolized further; for example,
in the bunting Zonotrichia leucophrys the 2hydroxyacyl-CoA that is formed is immediately
reduced to alkane-1,2-diol. 3-Hydroxy fatty acids
probably arise by hydration of a 2-enoyl-CoA,
and w-hydroxy fatty acids arise by the action of a
microsomal cytochrome P-450 monooxygenase
[108, 134]. a-Oxidation is the name given to the
process whereby the C-1 of a fatty acid is cleaved
off as CO2, and the C-2 is oxidized to a carboxyl
group. For example, in the uropygial gland, shortening of 4-methyl fatty acids leads to 3-methyl
fatty acids, the synthesis of which is otherwise
difficult to imagine. This pathway allows the
degradation of 3-methyl-branched fatty acids in
mammalian liver and kidney; these fatty acids
cannot be directly ~-oxidized. This is important,
for example, in the degradation of phytanic acid
(3,7,11,15-tetramethylpalmitinic acid) that arises
from phytol in plant foodstuffs [195]. Oxidation
of the last or penultimate C atom [00- or (00-1)oxidation] leads to the formation of (D- or «(D-1)hydroxy fatty acids and then to dicarbonic acid,
which may be shortened still further by Boxidation. These reactions involve the participation of cytochrome P-450, require molecular oxygen and NADPH and, in addition to their occurrence in the mammalian liver and kidney and in
the uropygial gland, have been described in tr
liver of the frog Rana catesbeiana [134, 1 (
188, 195]. PUFAs can be oxidized to hyClacids by lipogenases and reduced
hydroxy acids with internal substi'
ent types of mammalian blood cell
15 Lipids
boxylated to D-methylmalonyl-CoA, isomerized
to L-methylmalonyl-CoA, and then converted
by the cobalamin-dependent methylmalonyl-CoA
mutase to succinyl-CoA, which then enters the
citrate cycle. The same reactions but operating in
the opposite direction are used by some invertebrates to produce propionate from succinate in
anaerobic metabolism, so long as vitamin B12 is
available (p. 552). Various invertebrates are relatively rich in cobalamin and catabolize propionate, just as the vertebrates do. In contrast, all
insects, regardless of whether they have a lot of
vitamin B12 (e.g. the termite Zootermopsis nevadensis) , a little (e.g. the cockroach Periplaneta
americana) or none at all (e.g. the housefly
Musca domestica) , degrade propionate by the
same cobalamin-independent pathway: this involves the formation of 3-hydroxypropionate by
modified ~-oxidation and its decarboxylation to
acetate. In the process, the C-2 of the propionate
becomes the carboxyl group of acetate, and the
C-3 becomes the methyl group [81].
The existence of a B-oxidation system in peroxisomes was first discovered in the endosperm of
beans and in the ciliate Tetrahymena; it was later
found in the rat liver and other vertebrate tissues
and is probably also present in all invertebrates
[65]. The ~-oxidation of fatty acids in Tetrahymena is restricted entirely to the peroxisomes.
Although the reactions in the peroxisomes are the
same as those which occur in the mitochondria,
the enzymes are completely different. Whereas
the first mitochondrial enzyme is a dehydrogenase, which introduces electrons into the respiration chain and yields two ATPs, the first peroxisomal enzyme is an FAD-containing acyl-CoA oxidase which produces H20 2 and yields no ATP. The
peroxide is removed by the catalase in the peroxisomes. Because acyl-CoA oxidase is practically
inactive against acyl residues with fewer than ten
C atoms, the animal peroxisomes, in contrast to
plant microbodies, cannot completely catabolize
fatty acids [235]. Enoyl-CoA hydratase and 3hydroxylacyl-CoA dehydrogenase are combined
with ~3,~2-enoyl-CoA isomerase to give a trifunctional enzyme. In contrast to the homotetrameric enzyme of the mitochondria, the 3ketoacyl-CoA thiolase is a homodimer. How fatty
acids reach the peroxisomes is still not known.
Carnitine is not required; the carnitine acyltransferase in the peroxisomes is possibly involved in
the transport of short-chain fatty acids into the
mitochondria [235].
The concept that by shortening long-chain
fatty acids the peroxisomes prepare them for
complete degradation in the mitochondria apparently does not hold for all vertebrates. Certain
copepod species, which form the principal diet
of herring, mackerel and other pelagic fish, are
relatively rich in wax esters with the alcohol
22:1(n-11); this is oxidized to the corresponding
fatty acids in the gut mucosa. However, investigations of the rainbow trout Salma gairdneri show
that the fatty acids are not processed in the peroxisomes, the activity of which decreases with
increasing chain length from C12 to CIS. The mitochondria are in fact adapted to the particular fatty
acid composition of the diet in that they can oxidize a wide fatty acid spectrum of 12: 0 to 22: 6
[94].
The hydroxylation of lignoceric acid 24: 0 to
cerebronic acid 2-0H-24:0, an important constituent of brain glycolipids, occurs by the action
of a mixed-function oxygenase [195]. In the uropygial glands of many birds, fatty acids are
hydroxylated at C-2, C-3 or terminal C atoms
and are then metabolized further; for example,
in the bunting Zonotrichia leucophrys the 2hydroxyacyl-CoA that is formed is immediately
reduced to alkane-1,2-diol. 3-Hydroxy fatty acids
probably arise by hydration of a 2-enoyl-CoA,
and w-hydroxy fatty acids arise by the action of a
microsomal cytochrome P-450 monooxygenase
[108, 134]. a-Oxidation is the name given to the
process whereby the C-1 of a fatty acid is cleaved
off as CO2, and the C-2 is oxidized to a carboxyl
group. For example, in the uropygial gland, shortening of 4-methyl fatty acids leads to 3-methyl
fatty acids, the synthesis of which is otherwise
difficult to imagine. This pathway allows the
degradation of 3-methyl-branched fatty acids in
mammalian liver and kidney; these fatty acids
cannot be directly ~-oxidized. This is important,
for example, in the degradation of phytanic acid
(3,7,11,15-tetramethylpalmitinic acid) that arises
from phytol in plant foodstuffs [195]. Oxidation
of the last or penultimate C atom [00- or (00-1)oxidation] leads to the formation of (D- or «(D-1)hydroxy fatty acids and then to dicarbonic acid,
which may be shortened still further by Boxidation. These reactions involve the participation of cytochrome P-450, require molecular oxygen and NADPH and, in addition to their occurrence in the mammalian liver and kidney and in
the uropygial gland, have been described in tr
liver of the frog Rana catesbeiana [134, 1 (
188, 195]. PUFAs can be oxidized to hyClacids by lipogenases and reduced
hydroxy acids with internal substi'
ent types of mammalian blood cell