The ETC (except for cytochrome c, see p. 75) is located in the inner mitochondrial membrane and is the final common pathway by which electrons derived from different fuels of the body flow to oxygen (O2), reducing it to H2O (see Fig. 6.6).
1. Mitochondrial membranes: The mitochondrion contains an outer and an inner membrane separated by the intermembrane space. Although the outer membrane contains special channels (formed by the protein porin), making it freely permeable to most ions and small molecules, the inner membrane is a specialized structure that is impermeable to most small ions, including H+, and small molecules such as ATP, ADP, pyruvate, and other metabolites important to mitochondrial function (Fig. 6.7). Specialized carriers or transport systems are required to move ions or molecules across this membrane. The inner mitochondrial membrane is unusually rich in proteins, over half of which are directly involved in oxidative phosphorylation. It also contains convolutions, called cristae, which greatly increase its surface area.
2. Mitochondrial matrix: The gel-like solution of the matrix (interior) of mitochondria is also rich in proteins. These include the enzymes responsible for the oxidation of pyruvate, amino acids, and fatty acids (by β-oxidation) as well as those of the tricarboxylic acid (TCA) cycle. The synthesis of glucose, urea, and heme occurs partially in the matrix of mitochondria. In addition, the matrix contains NAD+ and FAD (the oxidized forms of the two coenzymes that are required as electron acceptors), and ADP and Pi, which are used to produce ATP. [Note: The matrix also contains mitochondrial deoxyribonucleic acid (mtDNA), ribonucleic acid (mtRNA), and ribosomes.]
B. Organization
The inner mitochondrial membrane contains four separate protein complexes, called Complexes I, II, III, and IV that each contain part of the ETC (Fig. 6.8). These complexes accept or donate electrons to the relatively mobile electron carrier coenzyme Q (CoQ) and cytochrome c. Each carrier in the ETC can receive electrons from an electron donor and can subsequently donate electrons to the next acceptor in the chain. The electrons ultimately combine with O2 and H+ to form H2O. This requirement for O2 makes the electron transport process the respiratory chain, which accounts for the greatest portion of the body’s use of O2.
C. Reactions
With the exception of CoQ, which is a lipid-soluble quinone, all members of the ETC are proteins. These may function as enzymes as is the case with the flavin-containing dehydrogenases, may contain iron as part of an iron-sulfur (Fe-S) center, may contain iron as part of the porphyrin prosthetic group of heme as in the cytochromes, or may contain copper (Cu) as does the cytochrome a + a3 complex.
1.
NADH formation: NAD+ is reduced to NADH by dehydrogenases that remove two hydrogen atoms from their substrate. [Note: For examples of these reactions, see the discussion of the dehydrogenases of the TCA cycle, p. 112.] Both electrons but only one H+ (that is, a hydride ion [:H−]) are transferred to the NAD+, forming NADH plus a free H+.
2.
NADH dehydrogenase: The free H+ plus the hydride ion carried by NADH are transferred to NADH dehydrogenase, a protein complex (Complex I) embedded in the inner mitochondrial membrane. Complex I has a tightly bound molecule of flavin mononucleotide (FMN), a coenzyme structurally related to FAD (see Fig. 28.15, p. 384) that accepts the two hydrogen atoms (2 electrons + 2 H+), becoming FMNH2.