Image Based Question-69879

A young adult presented with a compound fracture in lower limb due to trauma.He is taken to surgery during which the Anesthesiologist notices increase rise in body temperature (102 degree F).

The operation is terminated as malignant hyperthermia is suspected.Which of the following component from the image is likely to be responsible for this phenomenon?

A. A

B. D

C. D

D. B

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Correct Answer » C Explanation

Ans:C. E

Electron Transfer Chain is shown in the image.

• A:Complex I
• B:Complex II
• C:Complex III
• D:Complex IV
• E:ATP Synthetase Complex.

• Patients with malignant hyperthermia experience uncoupling of Oxidative phosphorylation.

Oxidative Phosphorylation

Chemiosmosis:As the electrons are transferred,some electron energy is lost with each transfer.This energy is used to pump protons(H+) across the membrane from the matrix to the inner membrane space.A proton gradient is establised.

The higher negative charge in the matrix attracts the protons(H+) back from the intermembrane space to the matrix.The accumulation of protons in the intermembrane space drives protons into the matrix via diffusion.

Most protons move back to the matrix through ATP synthase.ATP synthase uses the energy of the proton gradient to synthesize ATP from ADP+Pi.

Uncouplers are amphipathic and increase the permeability of the lipoid inner mitochondrial membrane to protons,thus reducing the electrochemical potential and short circuiting the ATP synthase.

• In this way ,oxidation can proceed without phosphorylation,the energy thus released is not captured to form ATP ,rather it is released in the form of heat causing Hyperthermia.There are a number of physiological and pathological uncouplers.

• 2,4 Dinitrophenol,2,4-Dinitrocresol,CCCP,TCCP,Valinomycin,High dose of Aspirin are some of the uncouplers of Oxidative phosphorylation.

• The antibiotic Oligomycin completely blocks oxidation and phosphorylation by blocking the flow of protons through ATP Synthase.

• Long chain fatty acids,thyroxin,brown adipose tissue(thermogenin or th uncoupling protein is a physiological uncoupler found in brown adipose tissue that functions to generate body heat,particularly for the newborns and during hibernation in animals) and Calcium ions are some of the physiological uncouplers of oxidative phosphorylation.Excess calcium released in malignant hyperthermia is responsible for uncoupling of oxidative phosphorylation.

There are a number of site specific inhibitors of Electron Transport chain that act as poisons.

• Complex I is inhibited by Rotenone and Barbiturates like Amobarbital that inhibit electron transport by blocking the transfer from Fe-S to Q.

• Malonate is a competitive inhibitor of Complex II.

• Antimycin A and Dimercaprol inhibit the respiratory chain at Complex III.

• H2S,Carbon monoxide and Cyanide inhibit Complex IV.