transport of acyl residues through the inner mitochondrial membrane (Fig. 15.9) also plays a role in
the conversion process, but will be discussed only
in connection with ~-oxidative degradation. The
processes of lipid metabolism in invertebrates
appear to be distributed in a similar fashion
amongst various cell compartments, although
desaturation in insects has been demonstrated in
both microsomes (Locusta) , and mitochondria
(Drosophila), and even at different rates in both
cell organelles (Ceratitis) [63]. The enzymes
involved in the formation and hydrolysis of acylCoA have, up to now, been examined in detail only
in the mammals, where there are acyl-CoA synthetases and hydrolases with varying chain-length
specificity and intracellular localization [195].
Chain elongation is the most important reaction of fatty acid metabolism after desaturation.
Thus, the palmitic acids initially formed by the
FAS of all animals are mostly converted into
unsaturated fatty acids with 18-22 C atoms. The
mammalian elongation systems are localized in
the microsomes or mitochondria, and catalyse a
reaction sequence analogous to that of FAS,
except that cytochrome bs is involved together
with NADH as hydrogen donor. The rate-limiting
condensing enzyme of this process exists in at
least three different forms in the rat liver, with
specificity for saturated, mono- or polyunsaturated fatty acids [195, 209]. Tracer experiments
have shown a capacity for elongation in all investigated invertebrates, but nothing is known about
the enzymes involved. Of particular interest is the
formation of extremely long fatty acids from palmitic acid, as seen in the sponge Jaspis stellifera
[33], and as is assumed to be the case for the longchain fatty alcohols and acids in wax esters. The
shortening of long-chain fatty acids occurs by partial ~-oxidation in the peroxisomes.
The first double bond is introduced into position 9 in animals and most other eukaryotes, i.e.
the desatnrase begins counting from the carboxyl
C. Further double bonds usually arise between
existing bonds and the carboxyl end in animals,
and the methyl end in plants; the flagellate Euglena carries out both processes. The desaturases
are both position- and chain-length specific. The
stearoyl-CoA-il 9 -desaturase from the microsomes
of mammalian liver is the only such enzyme to
have been characterized in detail so far. This is, in
principle, an electron transport chain which utilizes O2 and electrons from reduced cytochrome b s
to introduce a double bond into stearoyl-CoA or
another acyl-CoA substrate. The system consists
of an NADH:cytochrome bs reductase, cyto15.1.3 Conversion of Fatty Acids
573
chrome bs and the actual desaturase; the
sequence of the latter, determined from the
cDNA, consists of 358 mostly non-polar amino
acids. Phospholipid stabilizes the structure and is
indispensable for the enzyme activity [195, 260].
The importance of the phospholipid component
has also been demonstrated for the microsomal
desaturase of insects, e.g. for the palmitoyl-CoAspecific enzyme from the Mediterranean fruit fly
Ceratitis capitata [168]. Mammalian liver apparently contains two il 9 -desaturases which attack
acyl-CoAs of different chain length. In mammals,
further double bonds can be introduced at positions 6, 5 and 4 (Fig. 15.7), but much less is known
about the corresponding specific desaturases than
about the il 9 -desaturases [124, 195].
The stearoyl-CoA-il 9 -desaturase of rat liver
microsomes is specific for acyl-CoA and inactive
against phosphatidylcholine-bound acids. In contrast, the il s - and il 6 -desaturases of the mammals
can process both acyl compounds, although it is
not clear which is the natural substrate. The plant
desaturases are specific for phospholipid-bound
fatty acids. In the ciliate Tetrahymena pyriformis,
palmitic acid can only be desaturated in the form
of a CoA derivative; the desaturation of oleic
acid to linoleic acid, which is not found in higher
animals, occurs in this case with phosphatidylcholine or oleoyl-CoA [137]. Bacteria desaturate
their fatty acids already during de novo synthesis
and cannot produce polyunsaturated fatty acids
(PUFAs). Desaturation of fatty acids still
attached to the FAS was described some time ago
for the dipterans Calliphora erythrocephala and
Drosophila melanogaster but has not been further
investigated [63].
Polyunsaturated fatty acids (PUFAs) are
essential components of membrane lipids and the
precursors of prostaglandins. It is claimed in
many textbooks that the specificity of their des aturases prevents all animals from producing linoleic acid 18:2(n-6) and a-linolenic acid 18:3(n-3);
these are therefore essential in the diet. On the
other hand, as the starting substance of the (n-6)
and (n-3) families, these can be further desaturated and elongated in animals, just like the (n-9)
fatty acids can be (Fig. 15.7). However, the situation is not quite so straightforward. The requirement for both fatty acids has been shown clearly
in the rat. The absence of both fatty acids from
the diet results in deficiency symptoms such as
dermatitis, slower growth and kidney damage.
However, rats can be normally reared through
two generations with linoleic acid alone, and linolenic acid alone only partially prevents the sym-
the conversion process, but will be discussed only
in connection with ~-oxidative degradation. The
processes of lipid metabolism in invertebrates
appear to be distributed in a similar fashion
amongst various cell compartments, although
desaturation in insects has been demonstrated in
both microsomes (Locusta) , and mitochondria
(Drosophila), and even at different rates in both
cell organelles (Ceratitis) [63]. The enzymes
involved in the formation and hydrolysis of acylCoA have, up to now, been examined in detail only
in the mammals, where there are acyl-CoA synthetases and hydrolases with varying chain-length
specificity and intracellular localization [195].
Chain elongation is the most important reaction of fatty acid metabolism after desaturation.
Thus, the palmitic acids initially formed by the
FAS of all animals are mostly converted into
unsaturated fatty acids with 18-22 C atoms. The
mammalian elongation systems are localized in
the microsomes or mitochondria, and catalyse a
reaction sequence analogous to that of FAS,
except that cytochrome bs is involved together
with NADH as hydrogen donor. The rate-limiting
condensing enzyme of this process exists in at
least three different forms in the rat liver, with
specificity for saturated, mono- or polyunsaturated fatty acids [195, 209]. Tracer experiments
have shown a capacity for elongation in all investigated invertebrates, but nothing is known about
the enzymes involved. Of particular interest is the
formation of extremely long fatty acids from palmitic acid, as seen in the sponge Jaspis stellifera
[33], and as is assumed to be the case for the longchain fatty alcohols and acids in wax esters. The
shortening of long-chain fatty acids occurs by partial ~-oxidation in the peroxisomes.
The first double bond is introduced into position 9 in animals and most other eukaryotes, i.e.
the desatnrase begins counting from the carboxyl
C. Further double bonds usually arise between
existing bonds and the carboxyl end in animals,
and the methyl end in plants; the flagellate Euglena carries out both processes. The desaturases
are both position- and chain-length specific. The
stearoyl-CoA-il 9 -desaturase from the microsomes
of mammalian liver is the only such enzyme to
have been characterized in detail so far. This is, in
principle, an electron transport chain which utilizes O2 and electrons from reduced cytochrome b s
to introduce a double bond into stearoyl-CoA or
another acyl-CoA substrate. The system consists
of an NADH:cytochrome bs reductase, cyto15.1.3 Conversion of Fatty Acids
573
chrome bs and the actual desaturase; the
sequence of the latter, determined from the
cDNA, consists of 358 mostly non-polar amino
acids. Phospholipid stabilizes the structure and is
indispensable for the enzyme activity [195, 260].
The importance of the phospholipid component
has also been demonstrated for the microsomal
desaturase of insects, e.g. for the palmitoyl-CoAspecific enzyme from the Mediterranean fruit fly
Ceratitis capitata [168]. Mammalian liver apparently contains two il 9 -desaturases which attack
acyl-CoAs of different chain length. In mammals,
further double bonds can be introduced at positions 6, 5 and 4 (Fig. 15.7), but much less is known
about the corresponding specific desaturases than
about the il 9 -desaturases [124, 195].
The stearoyl-CoA-il 9 -desaturase of rat liver
microsomes is specific for acyl-CoA and inactive
against phosphatidylcholine-bound acids. In contrast, the il s - and il 6 -desaturases of the mammals
can process both acyl compounds, although it is
not clear which is the natural substrate. The plant
desaturases are specific for phospholipid-bound
fatty acids. In the ciliate Tetrahymena pyriformis,
palmitic acid can only be desaturated in the form
of a CoA derivative; the desaturation of oleic
acid to linoleic acid, which is not found in higher
animals, occurs in this case with phosphatidylcholine or oleoyl-CoA [137]. Bacteria desaturate
their fatty acids already during de novo synthesis
and cannot produce polyunsaturated fatty acids
(PUFAs). Desaturation of fatty acids still
attached to the FAS was described some time ago
for the dipterans Calliphora erythrocephala and
Drosophila melanogaster but has not been further
investigated [63].
Polyunsaturated fatty acids (PUFAs) are
essential components of membrane lipids and the
precursors of prostaglandins. It is claimed in
many textbooks that the specificity of their des aturases prevents all animals from producing linoleic acid 18:2(n-6) and a-linolenic acid 18:3(n-3);
these are therefore essential in the diet. On the
other hand, as the starting substance of the (n-6)
and (n-3) families, these can be further desaturated and elongated in animals, just like the (n-9)
fatty acids can be (Fig. 15.7). However, the situation is not quite so straightforward. The requirement for both fatty acids has been shown clearly
in the rat. The absence of both fatty acids from
the diet results in deficiency symptoms such as
dermatitis, slower growth and kidney damage.
However, rats can be normally reared through
two generations with linoleic acid alone, and linolenic acid alone only partially prevents the sym-