Fundamentals of Molecular Biology. Part 1: Molecular Biology of the Cell - A. N. Ogodurtsov 2011

Oxidation of Glucose and Fatty Acids
Aerobic Oxidation in Mitochondria

Cell/35.html">Mitochondria are among the largest cellular Organelles, roughly comparable in size to an E. coli bacterium. In some Eukaryotic Cells, mitochondria can occupy up to 25% of the Cytosol.

A mitochondrion has two membranes: an outer membrane permeable to metabolites, and an inner membrane that houses the Electron Transport Chains and ATP synthesis systems (Figure 20).

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Figure 153 - Scheme of aerobic METABOLISM

Most oxidation reactions of Pyruvate and Fatty acids to CO₂ and H₂O, along with the coupled synthesis of ATP from ADP and P_i, take place on The inner mitochondrial membrane, within its cristae and matrix (Figure 154).

The reactions of pyruvate and Fatty acid oxidation to CO₂ and H₂O and the coupled synthesis of ATP involve numerous steps, but they can be divided into three groups of reactions, each occurring at a specific Location on the inner mitochondrial membrane:

1. Oxidation of Pyruvate and fatty acids to CO₂ coupled with the reduction of (a) NAD⊕ to NADH (Figure 151), and (b) FAD (flavin adenine dinucleotide) to FADH₂ (Figure 155). These electron carriers are often referred to as Coenzymes. Most reactions in this group occur in the matrix, while two of them are catalyzed by inner Membrane Proteins whose catalytic sites are oriented toward the matrix.

2. Electrons are transferred from NADH and FADH₂ to O₂, regenerating NAD⊕ and FAD. These reactions take place on the inner membrane and generate a proton-motive force.

3. The proton gradient is utilized to synthesize ATP via the F₀F₁ complex (ATP synthase) located on the inner membrane.

Figure 154 - Scheme of aerobic oxidation of pyruvate and fatty acids in the mitochondrion: 1 - pyruvate dehydrogenase, The Tricarboxylic Acid Cycle, and fatty acid metabolism; 2 - electron transport from NADH and FADH₂ to O₂ and Generation of the proton-motive force; 3 - ATP synthesis by ATP synthase (sometimes referred to as Complex V)

Cristae significantly increase the surface area of the inner mitochondrial membrane, thereby enhancing ATP yield. In a typical Liver cell mitochondrion, the inner membrane surface area is five times greater than that of the outer membrane. In mitochondria of cardiac or Skeletal Muscle cells (which have high ATP demands), the inner membrane surface area is three times larger still than in liver cells.

In plants, CARBOHYDRATES are stored as starch, which is hydrolyzed to glucose. Glycolysis then synthesizes pyruvate, whose molecules are transported into mitochondria just as in animal cells. Mitochondrial oxidation of pyruvate, accompanied by ATP synthesis, also occurs in photosynthetic cells during periods of darkness (dark reactions), and continuously in roots and other non-photosynthetic Tissues.

Figure 155 - Scheme of flavin adenine dinucleotide oxidation: a - oxidized form of FAD; b - reduced form of FADH₂. Ribityl: -CH₂(HCOH)₃CH₂-

Following The transport of pyruvate into the matrix, the enzyme pyruvate dehydrogenase (utilizing coenzyme A) catalyzes its conversion to acetyl-CoA (Figure 156).

In this reaction, unlike those catalyzed by Lactate dehydrogenase and Alcohol dehydrogenase (Figure 152), NAD⊕ is reduced to NADH.