Case study- Malignant hyperthermia (Electron transport chain and oxidative phosphorylation)

Basic concept

Electron Transport Chain

  • The electron transport chain (ETC) is a series of membrane-bound electron carriers (Figure-1)
  • Embedded in the mitochondrial inner membrane
  • Electrons from NADH and FADH2 are transferred to complexes of the ETC
  • Each complex transfers the electrons to the next complex in the chain.

COMPLEXES OF ELECTRON TRANSPORT CHAIN

  • Electrons flow through the respiratory chain through a redox span of 1.1 V from NAD+/NADH to O2/2H2O passing through three large protein complexes;
  • NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (Q) (also called ubiquinone);
  • Q-cytochrome c oxidoreductase (Complex III), which passes the electrons on to cytochrome ; and
  • Cytochrome c oxidase (Complex IV), which completes the chain, passing the electrons to O2 and causing it to be reduced to H2O .
  • Some substrates with more positive redox potentials than NAD+/NADH (eg, succinate) pass electrons to Q via, succinate Q reductase (Complex II), rather than Complex I.
  • The four complexes are embedded in the inner mitochondrial membrane, but Q and cytochrome c are mobile.
  • Q diffuses rapidly within the membrane, while Cytochrome c is a soluble protein.
  • The flow of electrons through Complexes I, III, and IV results in the pumping of protons from the matrix across the inner mitochondrial membrane into the intermembrane space (figure-1).

ETC

Figure-1- Organization of Electron transport chain

 ATP SYNTHASE COMPLEX

  • ATP synthase is embedded in the inner membrane, together with the respiratory chain complexes .
  • Several subunits of the protein form a ball-like shape arranged around an axis known as F1, which projects into the matrix and contains the phosphorylation mechanism .
  • F1 is attached to a membrane protein complex known as F0, which also consists of several protein subunits (Figure-2).
  • F0 spans the membrane and forms a proton channel.
  • The flow of protons through F0 causes it to rotate, driving the production of ATP in the F1 complex.

ATP synthase complex

Figure-2-The enzyme complex consists of an F0 sub complex which is a disk of “C” protein subunits. Attached is a Υ subunit in the form of a “bent axle.” Protons passing through the disk of “C” units cause it and the attached Υ subunit to rotate. The Υ subunit fits inside the F1 sub complex of three α and three βsubunits, which are fixed to the membrane and do not rotate.

Question of the day

A 23-year-old college foot ball player sustains a compound fracture on the field. He is taken to surgery, during which the anesthesiologist notes a significantly increased body temperature (102 0 F). The operation is terminated without completion, as malignant hyperthermia is suspected. Which of the following components of ETC is likely to be responsible for this phenomenon?

A. Complex I

B. Complex II

C. Complex III

D. Complex IV

E. ATP synthase complex

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2 Responses

  1. Well done Leena ! Keep it up !

  2. Ans.E.ATP synthase complex

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