Mol Nutr Food Res. 2005 Nov;49(11):999-1013. Related Articles, Links
The relation of lipid peroxidation processes with atherogenesis: a new
theory on atherogenesis.
Spiteller G.
Department of Organic Chemistry, University of Bayreuth, Bayreuth,
Germany. [email hidden]
The extremely high sensitivity of polyunsaturated fatty acids (PUFAs)
to oxygen is apparently used by nature to induce stepwise appropriate
cell responses. It is hypothesized that any alteration in the cell
membrane structure induces influx of Ca2+ ions. Ca2+ ions are required
to activate degrading enzymes, such as phospholipases and lipoxygenases
(LOX) that transform PUFAs bound to membrane phospholipids to
lipidhydroperoxides (LOOHs). Enzymatic reduction products of LOOHs seem
to serve as ligands of proteins, which induce gene activation to
initiate a physiological response. Increasing external impact on cells
is connected with deactivation of LOX, liberation of the iron ion in
its active center followed by cleavage of LOOH molecules to LO *
radicals. LO * radicals induce a second set of responses leading to
generation of unsaturated aldehydic phospholipids and unsaturated
epoxyhydroxy acids that contribute to induction of apoptosis. Finally
peroxyl radicals are generated by attack of LO * radicals on
phospholipids. The latter attack nearly all types of cell constituents:
Amino- and hydroxyl groups are oxidized to carbonyl functions, sugars
and proteins are cleaved, molecules containing double bonds such as
unsaturated fatty acids or cholesterol suffer epoxidation. LOOH
molecules and iron ions at the cell wall of an injured cell are in
tight contact with phospholipids of neighboring cells and transfer to
these reactive radicals. Thus, the damaging processes proceed and cause
finally necrosis except the chain reaction is stopped by scavengers,
such as glutathione. Consequently, PUFAs incorporated into
phospholipids of the cell wall are apparently equally important for the
fate of a single organism as the DNA in the nucleus for conservation of
the species. This review intends to demonstrate the connection of cell
alteration reactions with induction of lipid peroxidation (LPO)
processes and their relation to inflammatory diseases, especially
atherosclerosis and a possible involvement of food. Previously it was
deduced that food rich in cholesterol and saturated fatty acids is
atherogenic, while food rich in n-3 PUFAs was recognized to be
protective against vascular diseases. These deductions are in
contradiction to the fact that saturated fatty acids withstand
oxidation while n-3 PUFAs are subjected to LPO like all other PUFAs.
Considering the influence of minor food constituents a new theory about
atherogenesis and the influence of n-3 PUFAs is represented that might
resolve the contradictory results of feeding experiments and chemical
experiences. Cholesterol-PUFA esters are minor constituents of
mammalian derived food, but main components of low density lipoprotein
(LDL). The PUFA part of these esters occasionally suffers oxidation by
heating or storage of mammalian derived food. There are indications
that these oxidized cholesterol esters are directly incorporated into
lipoproteins and transferred via the LDL into endothelial cells where
they induce damage and start the sequence of events outlined above. The
deduction that consumption of n-3 PUFAs protects against vascular
diseases is based on the observation that people living on a fish diet
have a low incidence to be affected by vascular diseases. Fish are rich
in n-3 PUFAs; thus, it was deduced that the protective properties of a
fish diet are due to n-3 PUFAs. Fish, fish oils, and vegetables contain
besides n-3 PUFAs as minor constituents furan fatty acids (F-acids).
These are radical scavengers and are incorporated after consumption of
these nutrients into human phospholipids, leading to the assumption
that not n-3 PUFAs, but F-acids are responsible for the beneficial
efficiency of a fish diet.
PMID: 16270286 [PubMed - in process]
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