Nutrition and Metabolism of Lipids 105Plasma and milk lipids
In a way, plasma and milk lipids are an exception to
the general rule distinguishing membrane and storage
lipids. Plasma and milk lipids are present mostly as
lipoproteins, comprising mostly phospholipids and
cholesterol in the surrounding membrane and TAG
in the core (see Section 6.5). Plasma lipids contain the
only signifi cant pool of free fatty acids or NEFAs in
the body. Free fatty acids are not components of lipo-
proteins but are transported bound to albumin. They
are liberated mostly from adipose tissue when plasma
glucose and insulin are low. Plasma also contains pro-
portionally more fatty acids esterifi ed to cholesterol
(cholesteryl esters) than are found in tissues.
Whole body content and organ profi le of
fatty acids
An estimate of the whole body content of lipids in a
healthy adult human is given in Table 6.5. Additional
body fat is deposited during pregnancy, but the fatty
acid composition remains similar to that of nonpreg-
nant adults and refl ects dietary fat intake. The total lipid
content of plasma rises in the third trimester, with a
proportionally greater increase in saturated fatty acids
than PUFAs. This downward trend in the percentage of
PUFA towards term has led to some concern about the
possible adverse consequences for the fetus of defi -
ciency of PUFA. However, the actual amount of PUFA
in blood lipids rises but less so than for saturated fatty
acids; resulting in a proportional decrease in PUFA.
Soon after birth, body lipid composition starts to
change. Brain cholesterol rises moderately from under
40% to nearly 50% of brain lipids. Docosahexaenoate
also rises rapidly in brain lipids, followed a little later
by an increasing content of long-chain saturates and
monounsaturates as myelin develops. Adipose tissue
contains very little linoleate or α-linolenate at birth
but their content increases rapidly with milk feeding.
Plasma cholesterol is relatively low at birth and in
infancy, but increases by more than twofold by
adulthood.
In general, regardless of the profi le of dietary fatty
acids, saturated and monounsaturated fatty acids pre-
dominate in adipose tissue, whereas there is a closer
balance between saturates, monounsaturates, and
polyunsaturates in structural lipids. Long-chain
PUFAs such as docosahexaenoate are present in high
concentrations in specialized membranes, including
those of the retina photoreceptor, in synapses of the
brain, and in sperm.6.7 Long-chain fatty acid metabolism
Synthesis
Synthesis of fatty acids occurs in the cytosol. It begins
with acetyl-CoA being converted to malonyl-CoA by
acetyl-CoA carboxylase, an enzyme dependent on
biotin. Malonyl-CoA and a second acetyl-CoA then
condense via β-ketothiolase. This is subsequently
reduced, dehydrated, and then hydrogenated to yield
a four-carbon product that recycles through the same
series of steps until the most common long-chain
fatty acid product, palmitate, is produced (Figure
6.10). Acetyl-CoA is primarily an intramitochondrial
product. Thus, the transfer of acetyl-CoA to the
cytosol for fatty acid synthesis appears to require its
conversion to citrate to exit the mitochondria before
being reconverted to acetyl-CoA in the cytosol.
There are three main features of long-chain fatty
acid synthesis in mammals:
1 inhibition by starvation
2 stimulation by feeding carbohydrate after fasting
3 general inhibition by dietary fat.
Carbohydrate is an important source of carbon for
generating acetyl-CoA and citrate used in fatty acid
synthesis. Enzymes of carbohydrate metabolism also
help to generate the NADPH needed in fatty acid
synthesis. Acetyl-CoA carboxylase is a key control
point in the pathway and is both activated and induced
to polymerize by citrate. Acetyl-CoA carboxylase isTable 6.5 Body fat content of major fatty acids in humans
Fatty acid Content (g)
Palmitic acid 3320
Stearic acid 550
Oleic acid 6640
Linoleic acid 1560
Arachidonic acid 80
α-Linolenic acid 130
Eicosapentaenoic acid < 10
Docosahexaenoic acid < 10
Total 12 300
Data are based on a 70 kg adult human with 20% (14 kg) body fat.
Fat tissue contains about 88% actual fatty acids by weight, yielding
about 12.3 kg fatty acids in this example.