Question

Question: As described in Section 9.16, the leukotrienes, important components in the asthmatic response, are synthesized from arachidonic acid via the hydroperoxide 5-HPETE. Write a stepwise mechanism for the conversion of arachidonic acid to 5-HPETE with O₂ .

Short answer

Answer

Step-by-step solution

Leukotrienes

Leukotrienes are essential mediators of inflammatory and allergic mechanisms within the body. Arachidonic acid is converted to (5S)-5-hydroperoxy-6,8,11,14-eicosatetraneonoic acid (5-HPETE). Leukotrienes are synthesized from 5-HPETE by using a nonheme iron-rich enzyme 5-lipoxygenase (5-LO) and its activating protein (FLAP) in the leucocytes of the blood.

A molecule of oxygen abstracts a proton from arachidonic acid to form a free radical. The presence of the electron initiates homolysis of the neighboring double bond. The two free electrons would undergo a combination to form a new bond.

Formation of free radical

Series of free radical reactions

The free radical reacts with another molecule of oxygen. The compound is treated with another molecule of arachidonic acid to abstract a proton to form the hydroperoxide 5-HPETE.

Formation of 5-HPETE