602
15 Lipids
terminal third of the sequence is made up, like
collagen, of two dozen tripeptides with the structure Gly-X-Y, where hydroxyproline is common
in position Y. An SP-A-like protein of 43 kDa was
recently found in the rat and designated SP-D.
The surfactant proteins SP-B and SP-C are
extremely hydrophobic. Rat SP-B has 376 amino
acids and agrees in 69 % of its sequence with the
corresponding dog and human protein; SP-C has
only 34-35 amino acids. SP-B and SP-C arise
from larger precursors, whereby the precursor of
SP-C has 197 amino acids and is an integral membrane protein with its N-terminus retained in the
cytoplasm, i.e. it shows type-I orientation. The
transmembrane segment corresponds to the
mature SP-C [128, 274].
The bis-(monoacylglycero )phosphates are
composed of two or three glycerol molecules linked by phosphoric acid residues and esterified
with two to five fatty acids (Fig. 15.20f). These
rather unusual lipids are observed only in the
alveolar macrophages of humans and other mammals and during a rare pathological lipid accumulation, the Niemann-Pick disease [89]. Equally
uncommon in its distribution is N-acylphosphatidylethanolamine, which carries one of
the usual CI6 or CIS fatty acids bound in an amidelike fashion to the ethanolamine residue; this
occurs in amounts of up to 1 % of the total lipid in
the brains of pike and carp, but has otherwise
been found only in bacteria and plant seeds [186].
Hydrolytic cleavage of the fatty acid bound at
position sn-2 gives rise to Iysoglycerophospholipids, whose name derives from their lytic activity
on erythrocytes. They usually make up only a
small proportion of the structural lipids (Tables 15.14-15.16) but reach high levels in the blood
plasma of some mammals, e.g. 23 % in the rat
[89]. Haemolytic effects have also been attributed
to the ether phospholipids, which carry an alkyl
or l' -alkenyl residue instead of an acyl bound
ether-like at position sn-l (Fig. 15.20i,j). Hydrolytic cleavage of the l' -alkenyl residue and enolketo conversion gives rise to a long-chain aldehyde. From the term "plasmal" to describe this
aldehyde come the names "plasmalogens" for
1-(1' -alkenyl)-2-acyl-glycerophospholipids
and
"plasmal reaction" for their histochemical colour detection. Ether phospholipids are ubiquitous in the animal kingdom [63, 194, 265]. The
most common are the plasmalogens that are produced by dehydrogenation of the corresponding
l-alkyl-Iyso compound. In the elasmobranch and
marine invertebrates, l-alkyl-2-acyl-glycerophospholipids give rise to the common l-alkyl2,3-diacylglycerols, mentioned in Section 15.2.3
as storage lipids. The proportions of alkyl phospholipids and plasmalogens vary greatly with the
species, organ and phospholipid class. In the
mammals, the proportion of plasmalogens in the
phospholipids varies from 1 % in the liver to
23-25 % in the brain and muscle; thus, in humans
19 % of the total body phospholipids fall into this
category. From the elasmobranchs to the mammals, the plasmalogens make up between 46 and
68 % of the ethanolamine phospholipids in the
brain [58, 89]. A large part of the phospholipids
in many marine invertebrates (cnidarians, annelids, molluscs, arthropods, echinoderms and tunicates) consists of plasmalogens and l-alkyl-2acyl-glycerol compounds [38, 89]. Alkyl compounds also form a significant part of the membrane lipids of the ciliates Tetrahymena and Paramecium (Table 15.15).
15.4.2 Biosynthesis of the Phospholipids
The general scheme of phospholipid biosynthesis
in vertebrates has been known for more than two
decades (Fig. 15.22), although the nature of the
enzymes and the reaction mechanisms have by no
means been fully defined. In particular, it is not
known how the proportions of the different types
are regulated. This gap in our knowledge is due to
the fact that the enzymes of lipid biosynthesis are
bound tightly to the micro somes or mitochondrial
membranes and are difficult to approach experimentally [89]. For this reason, comparative biochemical investigations of lipid biosynthesis are
restricted almost entirely to tracer studies, which,
as it happens, are in general agreement with the
current scheme for the vertebrates. Both mitochondria and microsomes are capable of lipid biosynthesis but differ in the enzymes involved.
Thus, the methylation of phosphatidylethanolamine to phosphatidy1choline occurs only in the
endoplasmic reticulum, and cardiolipin synthesis
and the decarboxylation of phosphatidylserine to
phosphatidylethanolamine occur only in the
mitochondria. Both cell compartments contain
different isoenzymes of glycerophosphate acyltransferase (Fig. 15.22, reaction 1) and acyl-CoA
synthetase. We can only speculate about why lipid
biosynthesis is distributed between two cell compartments in such a complicated fashion. Prokaryotes produce mainly phosphatidylethanolamine, phosphatidylglycerol and cardiolipin;
hence, phosphatidylethanolamine and cardiolipin
are synthesized in the mitochondria, which,
15 Lipids
terminal third of the sequence is made up, like
collagen, of two dozen tripeptides with the structure Gly-X-Y, where hydroxyproline is common
in position Y. An SP-A-like protein of 43 kDa was
recently found in the rat and designated SP-D.
The surfactant proteins SP-B and SP-C are
extremely hydrophobic. Rat SP-B has 376 amino
acids and agrees in 69 % of its sequence with the
corresponding dog and human protein; SP-C has
only 34-35 amino acids. SP-B and SP-C arise
from larger precursors, whereby the precursor of
SP-C has 197 amino acids and is an integral membrane protein with its N-terminus retained in the
cytoplasm, i.e. it shows type-I orientation. The
transmembrane segment corresponds to the
mature SP-C [128, 274].
The bis-(monoacylglycero )phosphates are
composed of two or three glycerol molecules linked by phosphoric acid residues and esterified
with two to five fatty acids (Fig. 15.20f). These
rather unusual lipids are observed only in the
alveolar macrophages of humans and other mammals and during a rare pathological lipid accumulation, the Niemann-Pick disease [89]. Equally
uncommon in its distribution is N-acylphosphatidylethanolamine, which carries one of
the usual CI6 or CIS fatty acids bound in an amidelike fashion to the ethanolamine residue; this
occurs in amounts of up to 1 % of the total lipid in
the brains of pike and carp, but has otherwise
been found only in bacteria and plant seeds [186].
Hydrolytic cleavage of the fatty acid bound at
position sn-2 gives rise to Iysoglycerophospholipids, whose name derives from their lytic activity
on erythrocytes. They usually make up only a
small proportion of the structural lipids (Tables 15.14-15.16) but reach high levels in the blood
plasma of some mammals, e.g. 23 % in the rat
[89]. Haemolytic effects have also been attributed
to the ether phospholipids, which carry an alkyl
or l' -alkenyl residue instead of an acyl bound
ether-like at position sn-l (Fig. 15.20i,j). Hydrolytic cleavage of the l' -alkenyl residue and enolketo conversion gives rise to a long-chain aldehyde. From the term "plasmal" to describe this
aldehyde come the names "plasmalogens" for
1-(1' -alkenyl)-2-acyl-glycerophospholipids
and
"plasmal reaction" for their histochemical colour detection. Ether phospholipids are ubiquitous in the animal kingdom [63, 194, 265]. The
most common are the plasmalogens that are produced by dehydrogenation of the corresponding
l-alkyl-Iyso compound. In the elasmobranch and
marine invertebrates, l-alkyl-2-acyl-glycerophospholipids give rise to the common l-alkyl2,3-diacylglycerols, mentioned in Section 15.2.3
as storage lipids. The proportions of alkyl phospholipids and plasmalogens vary greatly with the
species, organ and phospholipid class. In the
mammals, the proportion of plasmalogens in the
phospholipids varies from 1 % in the liver to
23-25 % in the brain and muscle; thus, in humans
19 % of the total body phospholipids fall into this
category. From the elasmobranchs to the mammals, the plasmalogens make up between 46 and
68 % of the ethanolamine phospholipids in the
brain [58, 89]. A large part of the phospholipids
in many marine invertebrates (cnidarians, annelids, molluscs, arthropods, echinoderms and tunicates) consists of plasmalogens and l-alkyl-2acyl-glycerol compounds [38, 89]. Alkyl compounds also form a significant part of the membrane lipids of the ciliates Tetrahymena and Paramecium (Table 15.15).
15.4.2 Biosynthesis of the Phospholipids
The general scheme of phospholipid biosynthesis
in vertebrates has been known for more than two
decades (Fig. 15.22), although the nature of the
enzymes and the reaction mechanisms have by no
means been fully defined. In particular, it is not
known how the proportions of the different types
are regulated. This gap in our knowledge is due to
the fact that the enzymes of lipid biosynthesis are
bound tightly to the micro somes or mitochondrial
membranes and are difficult to approach experimentally [89]. For this reason, comparative biochemical investigations of lipid biosynthesis are
restricted almost entirely to tracer studies, which,
as it happens, are in general agreement with the
current scheme for the vertebrates. Both mitochondria and microsomes are capable of lipid biosynthesis but differ in the enzymes involved.
Thus, the methylation of phosphatidylethanolamine to phosphatidy1choline occurs only in the
endoplasmic reticulum, and cardiolipin synthesis
and the decarboxylation of phosphatidylserine to
phosphatidylethanolamine occur only in the
mitochondria. Both cell compartments contain
different isoenzymes of glycerophosphate acyltransferase (Fig. 15.22, reaction 1) and acyl-CoA
synthetase. We can only speculate about why lipid
biosynthesis is distributed between two cell compartments in such a complicated fashion. Prokaryotes produce mainly phosphatidylethanolamine, phosphatidylglycerol and cardiolipin;
hence, phosphatidylethanolamine and cardiolipin
are synthesized in the mitochondria, which,