BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART II. GENERATION AND STORAGE OF METABOLIC ENERGY

CHAPTER 14. OXIDATIVE PHOSPHORYLATION

Summary

In Oxidative Phosphorylation, a proton gradient across The inner mitochondrial membrane couples ATP synthesis to the flow of electrons from NADH or FADH₂ to O₂. Electron transport through three asymmetrically oriented transmembrane complexes drives the extrusion of protons from the mitochondrial matrix, generating a Membrane Potential. ATP synthesis is driven by the reverse flow of protons back into the matrix through a channel within the ATP-synthesizing complex, known as mitochondrial ATPase. Oxidative phosphorylation exemplifies a central concept in Bioenergetics: the Transduction of Free energy via proton gradients.

The electron carriers of the Respiratory Chain in the inner mitochondrial membrane include flavins, iron-sulfur clusters, Quinones, and cytochrome heme groups. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q reductase, the first of the three complexes, which also contains Fe-S centers. Electrons then emerge in QH₂, the reduced form of ubiquinone (Q). Highly mobile, QH₂ transports its electrons to QH₂-cytochrome c reductase, a complex containing Cytochromes b and c, along with an Fe-S center. This second complex reduces cytochrome c, a Water-soluble peripheral membrane protein. Like Q, cytochrome c is a mobile carrier that shuttles electrons to cytochrome c oxidase, the third complex, which contains cytochromes a and a₃. A copper ion in this oxidase transfers the electrons to the ultimate acceptor, O₂, yielding H₂O.

The passage of a pair of electrons through each of these three complexes generates a proton gradient sufficient to drive the synthesis of one molecule of ATP. Consequently, three ATP molecules are formed per oxidized NADH, whereas only two ATP molecules are generated per oxidized FADH₂, because its electrons enter the chain at the level of QH₂, bypassing the first proton-pumping site. Similarly, only two ATP molecules are produced upon The oxidation of cytosolic NADH, as one ATP equivalent is consumed in transporting the electrons into the Cell/35.html">Mitochondria via the glycerol phosphate shuttle. The entry of ADP into the mitochondria is coupled to the export of ATP through a process known as facilitated exchange diffusion. Complete oxidation of a glucose molecule to CO₂ and H₂O yields 36 molecules of ATP. Under normal conditions, Electron transport is tightly coupled to phosphorylation; the oxidation of NADH and FADH₂ occurs only when ADP is simultaneously phosphorylated to ATP. This regulation, termed Respiratory Control, can be uncoupled by agents such as DNP, which dissipates the proton gradient by carrying protons across the inner mitochondrial membrane.