Introduction to Human Nutrition

106 Introduction to Human Nutrition

inhibited by long-chain fatty acids, especially PUFAs
such as linoleate. This is probably one important
negative feedback mechanism by which both starva-
tion and dietary fat decrease fatty acid synthesis. High
amounts of free long-chain fatty acids would also
compete for CoA, leading to their β-oxidation.
Elongation of palmitate to stearate, etc., can occur in
mitochondria using acetyl-CoA, but is more com-
monly associated with the endoplasmic reticulum
where malonyl-CoA is the substrate.
Humans consuming >25% dietary fat synthesize
relatively low amounts of fat (<2 g/day). Compared
with other animals, humans also appear to have a
relatively low capacity to convert stearate to oleate
and linoleate or α-linolenate to the respective longer
chain polyunsaturates. Hence, the fatty acid profi les
of most human tissues generally refl ect the intake of
dietary fatty acids; when long-chain n-3 PUFAs are
present in the diet, this is evident in both free-living
humans as well as in experimental animals. Neverthe-
less, fatty acid synthesis is stimulated by fasting/
refeeding or weight cycling, so these perturbations in

normal food intake can markedly alter tissue fatty

acid profi les.

Oxidation

β-Oxidation is the process by which fatty acids are

utilized for energy. Saturated fatty acids destined for

β-oxidation are transported as CoA esters to the outer

leafl et of mitochondria by FABP. They are then

translocated inside the mitochondria by carnitine

acyl-transferases. The β-oxidation process involves

repeated dehydrogenation at sequential two-carbon

steps and reduction of the associated fl avoproteins

(Figure 6.11). Five ATP molecules are produced

during production of each acetyl-CoA. A further 12

ATP molecules are produced after the acetyl-CoA

condenses with oxaloacetate to form citrate and goes

through the tricarboxylic acid cycle.

C—C—CO (Malonyl SA) + C—CO (Acetyl SS)

Condensation

CO 2 + C—CO—C—CO (Acetoacetyl SA)

C—COH—C—CO (β-Hydroxybutyryl SA)

C—C—C—CO (Butyryl SA)

First reduction

Dehydration

Second reduction

C—C C—CO (Crotonyl SA)

H 2 O

——

Figure 6.10 Principal steps in fatty acid synthesis. The individual
steps occur with the substrate being anchored to the acyl carrier
protein. SA, S-acyl carrier protein; SS, S-synthase.

FAD

FADH

NAD1

NADH

CoA

R—CH 2 —CH 2 —CH 2 —CO—CoA

H 2 O

R—CH 2 —CH—CH—CO—CoA—

R—CH 2 —CHOH—CH 2 —CO—CoA

R—CH 2 —CO—CH 2 —CO—CoA

R—CH 2 —CO—CoA CH 2 —CO—CoA

Figure 6.11 Principal steps in β-oxidation of a saturated fatty acid.

The steps shown follow fatty acid “activation” (binding to coenzyme

A) and carnitine-dependent transport to the inner surface of the mito-

chondria. Unsaturated fatty acids require additional steps to remove

the double bonds before continuing with the pathway shown. FAD,

fl avin adenine dinucleotide; FADH reduced fl avin adenine dinucleo-

tide; R, 12 carbons.