Other acyl-CoA molecules such as
propionyl-CoA can be used as primers by
the fatty acid synthase complex. In this
case, odd-carbon numbered fatty acids will
be produced, most commonly of 15 or 17
carbon length. In addition, methylmalonyl-
CoA can replace malonyl-CoA in the
elongation reactions, resulting in branched-
chain (methyl-branched) fatty acids. In
most lipogenic tissues, these fatty acids are
only minor products, but in sebaceous
(skin) glands of some species the produc-
tion of methyl-branched fatty acids may be
substantial (Smith, 1994). In ruminants,
higher concentrations of odd-chain and
branched-chain fatty acids are found in
milk and adipose tissue because of the
greater synthesis of these fatty acids by
rumen bacteria.
In adipose tissue, the predominant
product of the lipogenic pathway is
palmitic acid. In the mammary gland of
lactating animals, however, large quantities
of fatty acids <16 carbons in length are
synthesized. This is due to the action of
specific chain-terminating mechanisms,
which differ between ruminants and non-
ruminants. In ruminants, the fatty acid
synthase complex allows the release of
short- and medium-chain fatty acyl-CoA
esters, which are incorporated rapidly into
milk fat. In non-ruminants, a specific
enzyme, thioesterase II, is responsible for
hydrolysing the thioester bond of the 8–14
carbon acyl chain, thus releasing the
medium-chain fatty acids (Smith, 1994).
Elongation and desaturation
The end-product of the de novo lipogenic
pathway in animal tissues is usually
palmitic acid, yet this fatty acid constitutes
only 20–30% of total fatty acids in adipose
tissue lipids (Rule et al., 1995).
Considerable amounts of stearic (18:0) and
oleic (18:1) acids are present in adipose
tissue lipids, and may arise either from
intestinally derived triacylglycerol-rich
lipoproteins or by conversion from
palmitic acid in adipose tissue. Elongation
of palmitic acid (16:0) to stearic acid occurs
by the action of fatty acid elongase, found
in the microsomal fraction (endoplasmic
reticulum) of adipocytes. Malonyl-CoA is
the source of the additional two carbons.
Fatty acid elongase is found in much larger
activities in bovine adipose tissue than in
mammary gland, liver, muscle or intestinal
mucosa (Smith, 1995).
The concentration of stearic acid in
tissue lipids is regulated by the presence of
stearoyl-CoA desaturase (9 desaturase),
which converts stearic acid to oleic acid.
This microsomal enzyme is a mixed
function oxidase that inserts a double bond
nine carbons from the methyl end of the
fatty acid. Considerable activity of stearoyl-
CoA desaturase is found in mammary
gland, muscle and duodenal muscosa, but
little activity is found in bovine liver
(Smith, 1995). The primary function of the
enzyme seems to be to regulate lipid
fluidity by preventing excessive accumula-
tion of the very high-melting stearic acid.Glycerolipid synthesis
Few free (non-esterified) fatty acids are
found in the animal body; rather, most fatty
acids are found esterified to glycerol as
glycerolipids such as triacylglycerols and
phospholipids. In adipose tissue and the
lactating mammary gland, most fatty acids
are esterified to form triacylglycerols as a
non-toxic form of energy storage or for
transfer to the young, respectively. In liver
and other tissues, most fatty acids are
esterified to form phospholipids as com-
ponents of intracellular and plasma mem-
branes. The liver actively synthesizes
triacylglycerols when presented with high
concentrations of non-esterified fatty acids
from the blood.
The enzymes necessary for glycerolipid
biosynthesis are found in the microsomal
fraction of cells. The general pathways of
esterification of fatty acids are shown in
Fig. 5.3. Acyl chains from acyl-CoA are
transferred consecutively to glycerol-3-
phosphate produced via glycolysis.
Production of diacylglycerol (diglyceride)
from phosphatidate by phosphatidate
phosphohydrolase and subsequent produc-
tion of triacylglycerol from diacylglycerol by
diacylglycerol acyltransferase may be
regulatory steps for triacylglycerol synthesis,106 J.K. Drackley