The isoprostanes are
prostaglandin
Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...
-like compounds formed ''in vivo'' from the free radical-catalyzed
peroxidation
of
essential fatty acid
Essential fatty acids, or EFAs, are fatty acids that are required by humans and other animals for normal physiological function that cannot be synthesized in the body. As they are not synthesized in the body, the essential fatty acids al ...
s (primarily
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes.
Together with omega−3 fatty acids an ...
) without the direct action of
cyclooxygenase
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...
(COX) enzymes. These
nonclassical eicosanoid Nonclassic eicosanoids are biologically active Lipid signaling, signaling molecules made by oxygenation (medicine), oxygenation of twenty-carbon fatty acids other than the classic eicosanoids.
Terminology
:
"Eicosanoid" is the collective
term fo ...
s possess potent
biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
as
inflammatory mediators that augment the perception of
pain
Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
.
[
] These compounds are accurate markers of
lipid peroxidation
Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives.{{Cite journal , last1=Ayala , first1=Antonio , last2=Muñoz ...
in both animal and human models of
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
.
Elevated levels of isoprostanes are suspected of contributing to increased risk of heart attack in patients taking
Coxibs. Isoprostanes and their metabolites have also been shown to be elevated in the urine of cigarette smokers, and have been suggested as biomarkers of oxidative stress in smokers.
Abundance
Polyunsaturated fatty acids other than arachidonic acid are also vulnerable to reactive oxygen species and produce isoprostanes.
For example, in addition to the four classes of F2-isoprostanes that can arise from
arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes.
Together with omega−3 fatty acids an ...
, peroxidation of
eicosapentaenoic acid
Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega−3 fatty acid. In physiological literature, it is given the name 20:5(''n''−3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid wi ...
(EPA) is predicted to lead to the generation of six classes of F3 isoprostanes, α-linolenic and γ-linolenic acids to two classes of E1- and F1-isoprostanes, and
docosahexaenoic acid
Docosahexaenoic acid (DHA) is an omega−3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(''n''−3). It can be synthesized from alpha-linolenic acid or ...
to eight classes of D4-isoprostanes and eight classes of E4-isoprostanes. Each of the classes comprise up to eight racemic isomers, leading to an astounding number of isoprostane molecules.
History
The isoprostanes were reported in 1990 by L. Jackson Roberts and Jason D. Morrow in the Division of Clinical Pharmacology at Vanderbilt University.
[COX activity produces H2O2 which may non-enzymatically produce isoprostanes.][
{{cite journal , author=Morrow JD, Roberts LJ , title=The isoprostanes. Current knowledge and directions for future research , journal=Biochem. Pharmacol. , volume=51 , issue=1 , pages=1–9 , year=1996 , pmid=8534261 , doi=10.1016/0006-2952(95)02072-1
]
See also
*
Neuroprostanes
The neuroprostanes are prostaglandin-like compounds formed ''in vivo'' from the free radical-catalyzed peroxidation
of essential fatty acids (primarily docosahexaenoic acid) without the direct action of cyclooxygenase (COX) enzymes. The result ...
*
Prostaglandin
Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...
*
Isofurans
References
Prostaglandins