Introduction to Human Nutrition

Nutrition and Metabolism of Lipids 109

Chain elongation of saturated and unsaturated
fatty acids occurs primarily in the endoplasmic retic-
ulum, although it has also been demonstrated to
occur in mitochondria. Unlike the desaturation steps
immediately before and after, the elongation steps do
not appear to be rate limiting in the metabolism of
linoleate or α-linolenate.
Despite the capacity to insert at least three double
bonds in both n-3 and n-6 polyunsaturates, there is
no proof that a Δ^4 desaturase exists to insert the fi nal
double bond in docosapentaenoate (22:5n-6) or doc-
osahexaenoate (Figure 6.13). Rather, it appears that
the precursors to these two fatty acids undergo a
second elongation, repeated Δ^6 desaturation followed
by chain shortening in peroxisomes. This unexpect-
edly convoluted series of steps is corroborated by the
docosahexaenoate defi ciency observed in disorders
of peroxisomal biogenesis such as Zellweger’s
syndrome.

Hydrogenation

Opposite to the desaturation process is hydrogena-
tion or removal of unsaturated bonds in lipids. Rumen

bacteria are the only organisms known to have this

capability. As in chemical hydrogenation practiced by

the food industry, biohydrogenation in the rumen can

be incomplete, resulting in the formation of small

amounts of trans isomers, particularly of oleate, lino-

leate, and α-linolenate, which are found in milk fat.

Eicosanoids

Eicosanoids are 20-carbon, oxygen-substituted

cyclized metabolites of dihomo-γ-linolenate, arachi-

donate, or eicosapentaenoate. They are produced via

a cascade of steps starting with the cyclooxygenase or

lipoxygenase enzymes present in microsomes. The

main cyclooxygenase products comprise the classical

prostaglandins, prostacyclin and the thromboxanes.

The main lipoxygenase products are the leukotrienes

(slow-reacting substances of anaphylaxis) and the

noncyclized hydroperoxy derivatives of arachidonate

that give rise to the hepoxylins and lipoxins (Figure

6.14).

Eicosanoids are considered to be fast-acting local

hormones, the presence of which in the plasma and

urine is largely a spillover from localized production,

w 6 Polyunsaturates w 3 Polyunsaturates

Linoleic

γ-Linolenic

Dihomo-γ-Linolenic

Arachidonic

Adrenic

ω6-Docosapentaenoic Docosahexaenoic

α-Linolenic

Stearidonic

ω3-Eicosatrienoic

ω3-Docosapentaenoic

Eicosapentaenoic

Δ^6 Desaturation

Δ^5 Desaturation

Chain elongation

Chain elongation

Chain elongation,

peroxisomal

chain shortening

Figure 6.13 Conversion of linoleic (18:2n-6) and

α-linolenic (18:3n-3) acids to their respective longer

chain, more unsaturated polyunsaturates. In mem-

branes, linoleic and arachidonic acids are the prin-

cipal n-6 polyunsaturates, while docosahexaenoic

acid is the principal n-3 polyunsaturate. Hence,

these two families of fatty acids have different

affi nities for the desaturation and chain-elongation

enzymes. This pathway is principally based in the

endoplasmic reticulum but appears to depend on

peroxisomes for the fi nal chain shortening, which

involves 24 carbon intermediates that are not

illustrated.