Tricarboxylic acid cycle oxidative phosphorylation

F. Wu, F. Yang, KC Vinnakota, and DA Beard, Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysio logy. J. Biol. Chem. 282(34), 24525 24537 (2007). 

Senior, A.E. Shenatt, H.S.A. (1968). Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates. Biochem. J. 110,499-509. 

By the mid-1950s, therefore, it had become clear that oxidation in the tricarboxylic acid cycle yielded ATP. The steps had also been identified in the electron transport chain where this apparently took place. Most biochemists expected oxidative phosphorylation would occur analogously to substrate level phosphorylation, a view that was tenaciously and acrimoniously defended. Most hypotheses entailed the formation of some high-energy intermediate X Y which, in the presence of ADP and P( would release X and Y and yield ATP. A formulation of the chemical coupling hypothesis was introduced by Slater in 1953,... 

The metabolic machinery responsible for the heterotrophic respiration reactions is contained in specialized organelles called mitochondria. These reactions occur in three stages (1) glycolysis, (2) the Krebs or tricarboxylic acid cycle, and (3) the process of oxidative phosphorylation also known as the electron transport chain. As illustrated in... 

The net outcome is that each rotation of the tricarboxylic acid cycle converts one acetyl residue and two molecules of H2O into two molecules of CO2. At the same time, one GTP, three NADH+H"" and one reduced ubiquinone (QH2) are produced. By oxidative phosphorylation (see p. 122), the cell obtains around nine molecules of ATP from these reduced coenzymes (see p. 146). Together with the directly formed GTP, this yields a total of 10 ATP per acetyl group. 

As a catabolic pathway, it initiates the terminal oxidation of energy substrates. Many catabolic pathways lead to intermediates of the tricarboxylic acid cycle, or supply metabolites such as pyruvate and acetyl-CoA that can enter the cycle, where their C atoms are oxidized to CO2. The reducing equivalents (see p. 14) obtained in this way are then used for oxidative phosphorylation—I e., to aerobically synthesize ATP (see p. 122). 

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

Mitochondria are also described as being the cell s biochemical powerhouse, since—through oxidative phosphorylation (see p. 112)—they produce the majority of cellular ATP. Pyruvate dehydrogenase (PDH), the tricarboxylic acid cycle, p-oxidation of fatty acids, and parts of the urea cycle are located in the matrix. The respiratory chain, ATP synthesis, and enzymes involved in heme biosynthesis (see p. 192) are associated with the inner membrane. 

UNIT II Intermediary Metabolism Chapter 6 Bioenergetics and Oxidative Phosphorylation 69 Chapter 7 Introduction to Carbohydrates 83 Chapter 8 Glycolysis 89 Chapter 9 Tricarboxylic Acid Cycle 107 Chapter 10 Gluconeogenesis 115 Chapter 11 Glycogen Metabolism 123... 

Metabolic Strategies 227 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 242 The Tricarboxylic Acid Cycle 282 Electron Transport and Oxidative Phosphorylation 305 Photosynthesis 330 Structures and Metabolism of Oligosaccharides and Polysaccharides 356... 

This chapter is mainly concerned with the contribution of the tricarboxylic acid cycle to carbohydrate metabolism. The TCA cycle is the main source of electrons for oxidative phosphorylation, and thereby the major energetic sequence in the metabolism of aerobic cells or organisms. It serves as the main distribution center of metabo-... 

Kennedy and Lehninger discovered that the tricarboxylic acid cycle, fatty acid oxidation, and oxidative phosphorylation all take place in mitochondria. 

Mitochondria Tricarboxylic acid cycle, electron transport and oxidative phosphorylation, fatty acid oxidation, urea synthesis... 

Acetyl-CoA is oxidized to C02 by the Krebs cycle, also called the tricarboxylic acid cycle or citric acid cycle. The origin of the acetyl-CoA may be pyruvate, fatty acids, amino acids, or the ketone bodies. The Krebs cycle may be considered the terminal oxidative pathway for all foodstuffs. It operates in the mitochondria, its enzymes being located in their matrices. Succinate dehydrogenase is located on the inner mitochondrial membrane and is part of the oxidative phosphorylation enzyme system as well (Chapter 17). The chemical reactions involved are summarized in Figure 18.7. The overall reaction from pyruvate can be represented by Equation (18.5) ... 

The effect of nonfatal injuries such as a 2-hour period of bilateral hind-limb ischemia or a full-thickness scald of 20% of skin surface on the LDso of DNOC and its hyperthermic effect were evaluated in male rats (Stoner 1969). The intraperitoneal LDs° of DNOC was significantly (p<0.001) reduced from 24.8 to 26.2 mg/kg to 14 mg/kg DNOC when DNOC was given 1.5- 24 hours after either type of nonfatal injury. The authors concluded that the toxicity of DNOC was increased by previous trauma. These investigators proposed that this interaction was associated with sequential blocking of the tricarboxylic acid cycle with inhibition of citrate synthetase reaction during the early part of the response to the injury. Because DNOC acts as an uncoupler of oxidative phosphorylation, less ATP is produced. Therefore, the effects of trauma will be enhanced by an uncoupling agent such as DNOC. 

Actively respiring fungal cells possess a distinct mitochondrion, which has been described as the power-house of the cell (Fig. 4.2). The enzymes of the tricarboxylic acid cycle (Kreb s cycle) are located in the matrix of the mitochondrion, while electron transport and oxidative phosphorylation occur in the mitochondrial inner membrane. The outer membrane contains enzymes involved in lipid biosynthesis. The mitochondrion is a semiindependent organelle as it possesses its own DNA and is capable of producing its own proteins on its own ribosomes, which are referred to as mitoribosomes. 

When yeast cells grow aerobically, they can oxidize the pyruvate entirely to carbon dioxide and water. These reactions take place in structures called mitochondria. The reactions form a cyclic scheme termed the tricarboxylic acid cycle (TCA cycle) or Krebs cycle in which in one cycle, the substrate, pyruvate, is converted entirely to carbon dioxide and water (Fig. 3-10). Both substrate level phosphorylation and electron transport mediated phosphorylation occur during the process. In electron... 

Fig. 3-10 The biochemical pathway of the tricarboxylic acid cycle (TCA cycle). Pyruvate, generated from glycolysis (Fig. 3-8), enters the cycle as acetyl-CoA (acetyl-coenzyme A), and is then degraded through a series of reactions to a 4-carbon compound, oxaloacetate. The energy resulting from the reactions is stored as ATP, which is produced through electron transport and oxidative phosphorylation (see Fig. 3-11).

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