Food Lipids: Chemistry, Nutrition, and Biotechnology

The reciprocal response of the �6 and �5 compared with that of the �9 desaturase
is intriguing and may reflect a truly interactive regulation. For example, it
is not clear if the suppression of the �9 desaturase by growth hormone is an effect
solely of growth hormone or also of the metabolic products of the enhanced desaturation
by the �6 and �5 desaturases. Arachidonic acid, the product of the �6
and �5 desaturases, is known to directly down-regulate the adipose SCD [23]. Such
effects argue compellingly that the regulation of PUFA metabolism is sensitive to
the products of metabolism whether formed de novo or ingested. This will likely be
a focus of research in the future.
C. Elongation
The elongation of presynthesized fatty acids is critical to fatty acid metabolism in
animals. C16 and C18 fatty acids are the primary products of both plant and animal
fatty acid biosynthesis and, consequently, acyl chains longer than C18 must be elongated
post de novo synthesis. Many PUFAs critical to the structure and physiology
of animals are longer than C18; hence the need for an effective elongation system.
In addition, the sequential desaturase activities involved in producing more unsaturated
derivatives of n-fatty acids require intermediate elongation steps. This is not
accomplished through further cycling of fatty acid synthase, but rather through independent
activities located in the endoplasmic reticulum (ER) and the mitochondria.
These systems are quite distinct and even use different substrates for condensation.
Mitochondria and the ER add acetyl CoA and malonyl CoA as elongation substrate,
respectively [50]. Although the mitochondria are very active in the production of
acetyl CoA and � oxidation, the ER appears to possess the majority of elongase
activity. The ER system for acyl elongation appears to prefer unsaturated fatty acids
for further elongation, although this preference varies among tissues [50]. There is
evidence that a third elongase activity is present in the peroxisomes and that it is
related to the peroxisome proliferation response [51]. Although the majority of elongation
occurs in the liver, other tissues also express activity.
D. Peroxisomal PUFA Synthesis
Whereas the majority of fatty acid modifications involve elongation and/or desaturation,
some long chain PUFAs are produced by the removal of two carbons by one
cycle of oxidation. Long chain unsaturated fatty acids are retroconverted in peroxisomes
to produce acyl chains with two or four fewer carbon units. The most common
example of this type of acyl modification involves the synthesis of the long chain
PUFA, DHA. DHA is produced by the elongation of 22:5n-3 to 24:5n-3 followed
by a �6 desaturation and one cycle of � oxidation to produce 22:6n-3 [8,9,52]. There
is also evidence that the �6 desaturase involved in this pathway is distinct from the
�6 desaturase associated with typical PUFA production [53]. Several other fatty acids
are produced by this pathway, although it is not known if this is the primary source
of their biosynthesis. Voss et al. [54] showed that arachidonic acid can be produced
via the retroconversion pathway in rats injected with 22:4n-6. Hagve and Christophersen
[55] demonstrated that isolated rat liver cells were capable of retroconverting
22:4n-6 and 22:6n-3 to 20:4n-6 and 20:5n-3, respectively, suggesting that retroconversion
is actively utilized for the production of PUFAs in vivo. The semitoxic erucic
acid was retroconverted to oleic acid in cultured human fibroblasts [56].
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.