Introduction to Human Nutrition

112 Introduction to Human Nutrition

3 substrate and end-product inhibition
4 cofactor nutrients.

Specifi city
An n-6 PUFA cannot be converted to an n-3 or n-9
PUFA. Thus, defi ciency of one family of polyunsatu-
rates cannot be corrected by excess of those in a dif-
ferent family and, indeed, is exacerbated by excess
intake of the other families.

Competition
The three families of PUFAs appear to use a common
series of desaturases and chain elongases. The prefer-
ence of these enzymes is for the more unsaturated
fatty acids so, everything else being equal, more α-
linolenate will be desaturated than linoleate or oleate.
However, in practice, more linoleate is consumed
than α-linolenate and, as a result, more arachidonate
is produced endogenously than eicosapentaenoate.
Furthermore, this competition for desaturation and
chain elongation between linoleate and α-linolenate
can lead to exacerbation of symptoms of defi ciency
of one or other fatty acid family. Thus, as has been
demonstrated both clinically and experimentally,
excess linoleate intake using sunfl ower oil is a common
way to accelerate defi ciency of n-3 PUFA.

Inhibition
Excess linoleate or α-linolenate intake appears to
inhibit production of the respective long-chain prod-
ucts in the same fatty acid family, i.e., high α-lino-
lenate intake inhibits synthesis of docosahexaenoate.
Likewise, the main end-products of desaturation and
chain elongation tend to inhibit further metabolism
through this pathway, so arachidonate inhibits its
own synthesis. Similarly, dietary defi ciency of linole-
ate increases activity of the Δ^6 and Δ^5 desaturases,
presumably to restore depleted levels of long-chain
n-6 polyunsaturates such as arachidonate.

Cofactors
The cofactor requirements of the desaturation chain-
elongation enzymes are not yet well understood, but
a few relationships are known. The desaturases are
metalloenzymes containing iron, and iron defi ciency
therefore inhibits desaturase activity. Magnesium is
needed for microsomal desaturase activity in vitro.
Zinc defi ciency inhibits Δ^6 and Δ^5 desaturation, appar-
ently by interrupting the fl ow of electrons from

NADH. This effect is severe enough that inherited

forms of zinc defi ciency such as acrodermatitis

enteropathica cause a precipitous decline in plasma

arachidonate, greater than usually observed with

dietary defi ciency of n-6 polyunsaturates.

6.9 Nutritional and metabolic effects of

dietary fatty acids

Two types of issue exist in relation to the nutritional

and health implications of individual dietary lipids.

1 Whether synthesized endogenously or only

obtained from the diet, what are the specifi c mem-

brane, precursor, or metabolic effects of dietary

lipids beyond that of providing energy?

2 Whether synthesized endogenously or obtained

from the diet, does an excess amount of a dietary

lipid have benefi cial or deleterious implications for

health?

Short- and medium-chain fatty acids

Short-chain fatty acids (1–6 carbons) are mostly

derived from carbohydrate fermentation in the large

bowel and appear to be mainly used for energy,

although they are also substrates in several pathways.

Butyrate may have an important role as an energy

substrate for enterocytes. Medium-chain fatty acids

(8–14 carbons) naturally appear in mammalian milk

and are almost exclusively used as energy substrates.

They may also be chain elongated to palmitate.

Saturated fatty acids

Palmitate and stearate constitute a major proportion

of the acyl groups of membrane phospholipids and

all mammals have the capacity to synthesize them.

Hence, empirically, they presumably have an impor-

tant function in energy metabolism, cell structure,

normal development, and growth. The 20- to 24-

carbon saturates are also important constituents of

myelin. However, in any of these functions, it is

unlikely that a dietary source of saturates is necessary.

In fact, the brain is unable to acquire saturated

fatty acids from the circulation and relies on its

own endogenous synthesis for these fatty acids.

Furthermore, chronic excess intake and/or synthesis

of palmitate and stearate is associated with an

increased risk of diabetes and coronary artery

disease.