Biology of Disease

A number of fatty acids cannot be synthesized by the body including linoleic,

linolenic and arachidonic acid (Figure 10.4) and are precursors of many

biologically active and clinically relevant molecules, such as the eicosanoids

(prostaglandins, thromboxanes, prostacyclins and leukotrienes). These

molecules act like hormones and mediate a wide range of physiological

activities affecting, for example inflammatory responses, blood pressure and

clotting, reproductive activities and the sleep–wake cycle. Their actions are

local, affecting only cells near their sites of production, and they act at low

concentrations via second messengers (Chapter 7).

Humans, like all mammals, lack the enzymes needed to form a double bond

beyond C-9 or within the terminal seven carbon atoms of a fatty acid (Figure

10.5). Rather than the strict chemical convention of numbering carbon atoms

in fatty acids from the carboxyl group, the double bonds in fatty acids are often

numbered from the terminal or V carbon atom, giving rise to three families

of fatty acids with their first double bond occurring at positions V-3,V-6 and

V-9. These three families cannot be metabolically interconverted. The term

omega fatty acid has entered everyday English and the structures of a number

of examples are shown in Figure 10.6. Linoleic acid is an V-6 acid. Two forms of

linolenic acid occur, a V-3 type called @ linolenic acid (ALA) and the V-6 form,

F linolenic acid (GLA). Other V-3 EFAs are eicosapentaenoic acid (EPA) and

X]VeiZg&%/ DIET AND DISEASE

')' W^dad\nd[Y^hZVhZ

Figure 10.4 A computer generated model of

arachidonic acid. Oxygen atoms are shown in

red, carbon in black and hydrogen in gray.

H 3 CCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 COOH

1 or W 2 3 4 5 6 4 3 2 1 or A

W-series numbering Conventional numbering

Humans cannot form double

bonds in this region

6 5

Linoleic acid

A-linolenic acid

G-linolenic acid

Arachidonic acid

Eicosapentaenoic acid (EPA)

Docosahexaenoic acid (DHA)

COOH

COOH

COOH

COOH

COOH

COOH

W-6 series

W-3 series

W W W W W W

Figure 10.5 The numbering and

terminal unsaturation of fatty

acids.

Figure 10.6 The structures of some unsaturated

fatty acids.