Prostaglandins, from arachidonic

Figure 7.9 Pathway for the biosynthesis of prostaglandins from arachidonic acid. Steps 2 and 5 are radical addition reactions to 02 steps 3 and 4 are radical additions to carbon-carbon double bonds.

Lipoxygenases (LOX), cycloxygenases (COXs), and xanthine oxidase (XO) are metalloen-zymes whose catalytic cycle involves ROS such as lipid peroxyl radicals, superoxide, and hydrogen peroxide. LOXs and COXs catalyze important steps in the biosynthesis of leuco-trienes and prostaglandins from arachidonic acid, which is an important cascade in the development of inflammatory responses. XO catalyzes the ultimate step in purine biosynthesis, the conversion of xanthine into uric acid. XO inhibition is an important issue in the... 

In biological reactions, the situation is different from that in the laboratory. Only one substrate molecule at a time is present in the active site of the enzyme where reaction takes place, and that molecule is held in a precise position, with coenzymes and other necessary reacting groups nearby. As a result, biological radical reactions are both more controlled and more common than laboratory or industrial radical reactions. A particularly impressive example occurs in the biosynthesis of prostaglandins from arachidonic acid, where a sequence of four radical additions take place. The reaction mechanism was discussed briefly in Section 5.3. 

Figure 26-i I Synthesis of prostaglandins from arachidonic precursor. PG. Prostaglandin TX, thromboxane HPETE. HETE, HHT, l2-l-hydroxy-5,8, lO-heptadecatrienoic acid. 

NSAIDs exert their therapeutic action by blocking the enzyme cyclo oxygenase, which prevents the formation of prostaglandins from arachidonic acid, produced when tissue is damaged prostaglandins are major contributors... 

A summary of the synthesis of several prostaglandins from arachidonic acid. 

The production of reactive oxygen species e.g. superoxides is implicated in the biosynthesis of prostaglandins from arachidonic acid during tissue inflammation. Oxygen can be reduced to superoxide by plasma membrane bound NADPH-oxidase in rabbit and human cell neutrophils. The tsitsixenicins inhibited (> 80% at a concentration of approximately 30 pM) the production of superoxide in isolated rabbit neutrophils with only 94 retaining this level of activity on ten-fold dilution. The results observed with rabbit neutrophils cannot usually be directly extrapolated to human neutrophils and only 93 and 94 exhibited moderate activity when the assay was repeated using the latter neutrophils [91]-... 

Cascade of biosynthesis of prostaglandins from arachidonic acid and the role of aspirin (acetylsalicylic acid) in blocking biosynthesis and easing inflammation... 

Nowak, J., Kaijser, L. and Wennmalm, A. (1980). Cardiac synthesis of prostaglandins from arachidonic acid in man. Prostagl. Med., 4, 205-214... 

Lipid hydroperoxides play an important role in the biosynthesis of prostaglandins from arachidonic acid. The control of the concentration of hydroperoxides, also referred to as peroxide tone, is important for the maintenance of normal cell functions. Hydroperoxides can either stimulate cyclooxygenase activity at low concentrations (0.01 /jM) or inhibit this enzyme at high concentrations (1 M). The enzymes glutathione peroxidase and... 

Also known as aldehydo glycerides, or 2Vi glycerides) aldehydes attached to a glyceride or phospholipid Respirator enzyme that undergoes reduction and oxidation Enzyme catalysing the formation of prostaglandins from arachidonic acid... 

The enzymes that catalyze the synthesis of prostaglandins from arachidonic acid are known as cyclooxygenases, and the term COX refers to cyclooxygenase activity. By convention, the enzyme responsible for the production of... 

In 1971, Vane and Piper found that NSAIDs inhibit the biosynthesis of prostaglandins from arachidonic acid by preventing the substrate from binding to the COX enzyme active site. As it was... 

MECHANISM 26.4 BIOSYNTHESIS OF PROSTAGLANDINS FROM ARACHIDONIC ACID... 

Ibuprofen is the generic name for the pain reliever known by the trade names of Motrin and Advil. Like aspirin, ibuprofen acts as an anti-inflammatory agent by blocking the synthesis of prostaglandins from arachidonic acid. One step in a commercial synthesis of ibuprofen involves the reaction of a nucleophilic enolate with an electrophilic carbonyl group. In Chapter 24, we learn about the carbon-carbon bond-forming reactions of enolates with carbonyl electrophiles. 

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