Mechanism of Action of Nonsteroidal Anti-inflammatory Drugs

Presentation Summary : However placenta also requires these fatty acids for ... production of eicosanoids, ... Lower produce DHA and higher precursor ALA may be due to limited biosynthesis.

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Biosynthesis and metabolism of lipids mediators;

Metabolism1.0 Global and overview maps1.1 Carbohydrate metabolism1.2 Energy metabolism1.3 Lipid metabolism1.4 Nucleotide metabolism1.5 Amino acid metabolism1.6 Metabolism of other amino acids1.7 Glycan biosynthesis and metabolism1.8 Metabolism of cofactors and vitamins1.9 Metabolism of terpenoids and polyketides1.10 Biosynthesis of other secondary metabolites1.11 Xenobiotics biodegradation and metabolism1.12 Chemical structure transformation maps

of enzymes required for lipoxin biosynthesis

Lipids are digested and absorbed with the help of bile salts. Products of lipid digestion aggregate to form mixed micelles and are absorbed into the small intestine. Lipids are transported in the form of lipoproteins. Fatty acids are activated, transported across mitochondrial membrane with the help of carnitine transporter. β -oxidation of saturated fatty acids takes place in the mitochondrial matrix. Similarly oxidation of unsaturated and odd chain fatty acids also take place with additional reactions. Ketone bodies are formed in the liver but they are utilized by extra hepatic tissues. In uncontrolled diabetes mellitus and starvation, excessive ketone bodies are formed, leading to ketosis. Fatty acid biosynthesis takes place in the cytosol of cells. Fat gets deposited in the adipose tissue. Acetyl Coenzyme A is the precursor of fatty acid synthesis as well as cholesterol biosynthesis. Elevation of lipids in blood leads to deposition of cholesterol plaques in the arterial walls leading to atherosclerosis. Prostaglandins and leukotrienes are synthesized from twenty carbon unsaturated fatty acids. Phosphatidic acid is an important intermediate in the synthesis of glycerophospholipids. In sphingolipids, sphingosine is present as an alcohol.

(1976) Mechanism of action of the 12,13-epoxytrichothecene anguidine: an inhibitor of protein synthesis.
(1978) On the mechanism of action of the cytostatic drug anguidine and of the immunosuppressive agent ovalicin, two sesquiterpenes from fungi.

They are produced by almost all nucleated cells

PGE2 is another form of prostaglandin that is produced by the ovary, uterus and embryonic membranes. This form of prostaglandin also has other important roles including vasodilation, smooth muscle relaxation, and inhibition of the release of noradrenaline from sympathetic nerve terminals.

In females it's target tissue is the cervix (it is a potent cervical dilator), and the oviduct where it helps induce ovulation and the secretion of progesterone from the corpus luteum. PGE2 also plays an important role during labour where it aids the softening of the cervix in animals with a soft-type cervix(equine and human) and aids stimulation of uterine contractions. It can thus be used to prepare the tract for parturition.

PPT – EICOSANOIDS PowerPoint presentation ..

Relaxin is produced mainly by the corpus luteum in most species and in the placenta(main contributor in the equine) and ovaries throughout pregnancy. During pregnancy relaxin prevents the initiation of uterine contractions, together with progesterone. Relaxin accumulates troughtout pregnancy and is released in lare amounts a few days before partus. Its target organs are the cervix, vagina, pubic symphesis and related structures. Relaxin is responsible for the softening and relaxation of connective tissues in the cervix, muscles and ligaments in the pelvis prior to parturition. Estradiol priming is required for this. This relaxation of tissues via relaxin is performed in conjunction with prostaglandin.

Synthesis of Eicosanoids, Glycerolipids and Isoprenoids

Cholesterol biosynthesis
80% of endogenous cholesterol is formed in the liver. Enzymes involved in the synthesis are partly located in the endoplasmic reticulum and partly in the cytoplasm. Acetyl CoA is the precursor. HMG CoA, mevalonate, isopentenyl pyrophosphate, squalene are some of the important intermediate compounds formed during cholesterol synthesis. Cholesterol is transported in lipoprotein complexes. Elevation of lipids in blood leads to the deposition of cholesterol on the arterial walls leading to atherosclerosis.