What are the EICOSANOIDS? Importance of EICOSANOIDS

The term Eicosanoids refers to the oxidative metabolites of the Essential fatty Acids (EFA) containing 20 carbon atoms (in Greek Eicosa means twenty), and includes prostaglandins, prostacyclins, thromboxanes and leukotrienes. Prostaglandins (PG) were discovered by von Euler at about the same time that Burr and Burr discovered the EFA. The material was so named on the mistaken assumption that it originated from the prostate gland. There are more than 100 neutral PGs, isomers and their metabolites. Thromboxanes, prostacyclins and leukotrienes are derivatives of the PGs.

Eicosanoids Formation

The Eicosanoids formation may proceed through one of several alternative enzymatic routes. The precursor highly unsaturated fatty acids (HUFA) are esterified with cholesterol. They are made accessible on a stimulus reaching the cell surface, and acylhydrolases release the poly unsaturated fatty acids (PUFA) from the membrane, which will then be metabolized along one of three enzymatic routes.

1. The cyclooxygenase pathway
2. 5-lipooxygenase pathway
3. 12-lipooxygenase pathway

Dietary Fatty acids and Eicosanoids Metabolism

Desaturation and elongation of the essential fatty acids, linoleic (18:2,n-6) and alpha-linolenic (18:3,n-3) lead to the formation of dihomo-gamma-linolenic acid, DHLA (20:3,n-6), arachidonic acid, AA (20:4, N-6) and timnodonic acid (20:5,n-3;5,8,11,14,17-eicosa pentaenoic acid) more commonly known as EPA.these fatty acids are the precursors of prostaglandins of the 1,2 and 3 series, respectively. AA and EPA may be converted to leukotrienes of the 4 and 5 series, respectively. DHLA lacks a double bond at C5 and it is therefore not a substrate for 5-lipooxygenase.

Eicosanoids and Hemostasis

The major cyclooxygenase product in platelets is TXA2, a potent and important inducer of platelet aggregation and vaso-constriction. TXA2, formed during platelet activation, is highly unstable, with half life of 30 seconds, being rapidly hydrolyzed to inactive TXB2. Platelet aggregation is probably induced by prostaglandin endoperoxide PGG2 also. In vascular tissue the major eicosanoid released is prostacyclins, PGI2, a potent vasodilator and an inhibitor of platelet aggregation.

Greenland Eskimos have a low incidence of thrombotic episodes such as myocardial infarction, of atherosclerosis, of rheumatoid arthritis, of psoriasis and their bleeding tendancy is higher than that of other people.This has been attributed to high intake of fish food, containing large amount of EPA and its derivatives.

Lipid peroxidation and impact on Eicosanoids production

Many studies have implicated oxygen radicals and lipid peroxidation in various diseases. Poly unsaturated fatty acid (PUFA) is one component of cells that is liable to damage by free radicals. Attack by free radicals may result in;

1. The loss of PUFA cell membrane, with lowered ability to produce Eicosanoids.
2. The formation of lipid peroxides and related compounds which can themselves cause damage to other cellular component.

Above process can lead to formation of cancers.

Eicosanoids deficiency

Acute deficiency of essential fatty acids (EFA) in children results in growth failure and increased susceptible to infection. A chronic deficiency (a low ratio of EFA to non-essential fatty acids in the body) causes faulty structure of cell membranes and increased prevalence of chronic degenerative diseases such as atherosclerosis.

Requirements of Eicosanoids

In children, the minimal daily requirement of n-3 fatty acids has been estimated as 0.54% of total dietary energy.In adults it ranges from 0.2% to 0.3%. maximum being 0.5% to 1%, of total dietary energy.