Introduction to Human Nutrition

Nutrition and Metabolism of Lipids 111

ductus arteriosus shortly after birth. Many anti-infl am-
matory and anti-pyretic drugs are inhibitors of eico-
sanoid synthesis. One potentially dangerous side-effect
of inhibiting eicosanoid synthesis is gastric erosion
and bleeding. Receptor antagonists of leukotrienes are
effective in reducing the symptoms of asthma.

6.8 Nutritional regulation of long-chain
fatty acid profi les and metabolism

Phospholipids of all cellular and subcellular mem-
branes contain a diverse range of long-chain fatty
acids, the profi le of which is subject to both dietary
infl uence and endogenous control. A few organs,
notably the brain, maintain extraordinarily strict
control of their membrane composition. However,
the fatty acid profi le of most organs is usually respon-
sive to the infl uence of changes in dietary fatty acid
composition and other nutritional variables, yet
maintains the vital “gatekeeper” functions of all mem-
branes. Hence, when changes in dietary fat alter
membrane fatty acid profi les, appropriate membrane
fl uidity can be maintained by the addition or removal
of other lipids such as cholesterol. Insuffi cient energy
intake and the presence of disease have important
consequences for fatty acid synthesis, desaturation,
and chain elongation and, consequently, tissue fatty
acid profi les.

Saturates and monounsaturates

Inadequate energy intake increases macronutrient
oxidation, including fatty acids. Short-term fasting

followed by refeeding a carbohydrate-rich meal is the

classic way to stimulate fatty acid synthesis. Insulin is

implicated in this process. When repeated, fasting/

refeeding or weight cycling induces a gradual increase

in the proportion of saturated and monounsaturated

compared with PUFAs in tissues, especially body fat.

This shift occurs because of the increase in fatty acid

synthesis, easier oxidation of polyunsaturates, and the

inhibition of desaturation and chain elongation by

fasting. The implications of such an alteration in tissue

fatty acid profi les have not yet been extensively studied,

but probably involve changes in insulin sensitivity and

other hormone effects. Protein defi ciency also inhibits

desaturation and chain elongation of PUFAs.

Copper supplementation increases Δ^9 desaturase

activity in animals, resulting in higher oleate levels.

This effect was fi rst observed when copper was used

to reduce gastrointestinal infection in pigs, but also

led to softer back fat. Opposite to the effects of copper

supplementation, copper defi ciency inhibits synthesis

of both oleate and docosahexaenoate.

Polyunsaturated fatty acids

There are four key features of the nutritional regula-

tion of the profi les and metabolism of PUFAs. These

attributes govern the effects of defi ciency or excess of

one or more of these families of fatty acids almost as

much as their level in the diet. These key features

are:

1 specifi city within families

2 competition between families

Arachidonic acid

Eicosapentaenoic

acid

Dihomo-γ-

linolenic acid

Cyclooxygenase Lipoxygenase

1 series

PGs

2 series

PGs

3 series

PGs

3 series

LTs

4 series

LTs

5 series

LTs

Figure 6.15 Arachidonic acid is not

the only 20-carbon polyunsaturated

fatty acid that can be metabolized via

the cyclooxygenases and lipoxygen-

ases; both dihomo-γ-linolenic acid

(20:3n-6) and eicosapentaenoic acid

(20:5n-3) are well-established precur-

sors as well, and produce prostaglan-

dins (PGs) and leukotrienes (LTs) that

are frequently competitive with those

produced from arachidonate, thereby

neutralizing the effects of the arachido-

nate cascade (see Figure 6.14). This

provides a critical balance in the overall

reaction to cell injury.