Food Lipids: Chemistry, Nutrition, and Biotechnology

stability is a characteristic of some eicosanoids, stable analogs may be measured in
place of the compound of interest.
The leukotrienes are not cyclized and, as the name implies, contain three double
bonds in the acyl chain. Arachidonic acid is metabolized by 5-lipoxygenase to leukotriene
A 4. This eicosanoid can be metabolized by an epoxide hydrolase to leukotriene
B 4 or via glutathione S-transferase to leukotriene C 4. The latter reaction results
in the addition to the fatty acid of cysteine, glycine, and glutamic acid. Leukotriene
C 4 can then be metabolized to D 4 by �-glutamyltransferase, which removes the glutamic
acid. Finally, D 4 can be metabolized to leukotriene E 4 by cysteinyl-glycine
dipeptidase, which removes the glycine and leaves only the cysteine residue on the
acyl chain. These compounds are critical mediators of a variety of inflammatory
responses (e.g., anaphylaxis, increased vascular permeability, attraction of leukocytes
and their activation).
Other eicosanoid products include thromboxanes, which are synthesized by
platelets and cause platelet aggregation and vascular constriction. Finally, prostacyclin
(PGI 2) is produced by blood vessels and inhibits platelet aggregation. These
categories of eicosanoids do not appear to participate in regulation of immune responses;
rather, they are altered in response to the dietary manipulation that affect
the prostaglandins and leukotrienes.
Currently, there is considerable debate about the quantitative requirements for
�3 fatty acids; it is fairly well established that the (EFA) requirement of both rodents
and humans is on the order of 0.5% of energy. The EFA requirement is satisfied
primarily by intake of linoleic acid (there is relatively little arachidonic acid in commonly
consumed foods) plus consumption of a smaller amount of linolenic acid or
its fatty acid metabolites, which are concentrated in fish oils. Alterations in some
immune functions can be seen with both low and high intake of EFA. This can be
conceptualized as a curve with a flattened top (Fig. 2), in which the normal range
of immune function is seen over a wide range of adequate EFA intake, whereas
decreased immune responses are seen with either deficient or excessive intakes. The
presumptive primary mechanisms are changes in the membrane microenvironment
and/or precursors of the eicosanoids, although a number of other possible links have
been suggested.
II. IMMUNE SYSTEM
A brief review of the components of the immune system will facilitate an understanding
of the effects of dietary fat on the immune response. The immune system
is the most dispersed network of cells in the body that are not in physical contact
yet cooperate functionally. It is composed of both fixed and mobile cells that protect
against invading organisms and the development of abnormal (malignant) cells. If,
however, it overreacts to self, the result is autoimmunity; if it overreacts to nonself,
there is an allergic response. Some of these immune cells have very short lives but
others, which form the basis of immunological memory, exist for many years and
perhaps for the lifetime of the host. Fixed cells of the reticuloendothelial system
(RES) are found primarily in the liver, spleen, bone marrow, thymus, lymph nodes,
lungs, and intestines. Mobile cells are found throughout the circulation in high numbers,
which increase quickly in response to the presence of foreign antigens. It is
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.