Tricarboxylic acid transport

Carboxylic acids such as pyruvate, succinate, and citrate are transported into the matrix by the pyruvate transporter, the dicarboxylic acid transporter, and the tricarboxylic acid transporter, respectively. Pymvate transport operates as an antiporter with hydroxide ion. The other transporters are driven by concentration gradients for their substrates. For example, high concentrations of citrate in the matrix lead to export of citrate to the cytoplasm, where it can inhibit phospho-fmctokinase (see Chapter 9). 

FIGURE 20.1 Pyruvate produced hi glycolysis is oxidized in the tricarboxylic acid (TCA) cycle. Electrons liberated in this oxidation flow through the electron transport chain and drive the synthesis of ATP in oxidative phosphorylation. In eukaryotic cells, this overall process occurs in mitochondria. 

This complex consists of four subunits, all of which are encoded on nuclear DNA, synthesized on cytosolic ribosomes, and transported into mitochondria. The succinate dehydrogenase (SDH) component of the complex oxidizes succinate to fumarate with transfer of electrons via its prosthetic group, FAD, to ubiquinone. It is unique in that it participates both in the respiratory chain and in the tricarboxylic acid (TC A) cycle. Defects of complex II are rare and only about 10 cases have been reported to date. Clinical syndromes include myopathy, but the major presenting features are often encephalopathy, with seizures and psychomotor retardation. Succinate oxidation is severely impaired (Figure 11). 

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). 

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... 

Marine organisms concentrate metals in their tissues and skeletal materials. Many of these trace metals are classified as micronutrients because they are required, albeit in small amounts, for essential metabolic functions. Some are listed in Table 11.4, illustrating the role of metals in the enzyme systems involved in glycolysis, the tricarboxylic acid cycle, the electron-transport chain, photosynthesis, and protein metabolism. These micronutrients are also referred to as essential metals and, as discussed later, have the potential to be biolimiting. 

Under aerobic conditions, the pyravate is oxidized to CO and H O via the tricarboxylic acid or Krebs cycle and the electron transport system. The net yield for glycolysis followed by complete oxidation is 38 moles ATP per mole glucose, although there is evidence that the yield for bacteria is 16 moles ATP per mole glucose (Aiba et al., 1973). Thus, 673 kcal are liberated per mole glucose, much of which is stored as ATP. 

The most important process in the degradation of fatty acids is p-oxidation—a metabolic pathway in the mitochondrial matrix (see p. 164). initially, the fatty acids in the cytoplasm are activated by binding to coenzyme A into acyl CoA [3]. Then, with the help of a transport system (the carnitine shuttle [4] see p. 164), the activated fatty acids enter the mitochondrial matrix, where they are broken down into acetyl CoA. The resulting acetyl residues can be oxidized to CO2 in the tricarboxylic acid cycle, producing reduced... 

During periods of hunger, muscle proteins serve as an energy reserve for the body. They are broken down into amino acids, which are transported to the liver. In the liver, the carbon skeletons of the amino acids are converted into intermediates in the tricarboxylic acid cycle or into acetoacetyl-CoA (see p. 175). These amphibolic metabolites are then available to the energy metabolism and for gluconeogenesis. After prolonged starvation, the brain switches to using ketone bodies in order to save muscle protein (see p. 356). 

This type of effect can occur in all tissues and is caused by a metabolic inhibitor such as azide or cyanide, which inhibits the electron transport chain. Inhibition of one or more of the enzymes of the tricarboxylic acid cycle such as that caused by fluoroacetate (Fig. 6.7) also results in inhibition of cellular respiration (for more details of cyanide and fluoroacetate see chap. 7). 

Many of the biochemical processes that generate chemical energy for the cell take place in the mitochondria. These organelles contain the biochemical equipment necessary for fatty acid oxidation, di- and tricarboxylic acid oxidation, amino acid oxidation, electron transport, and ATP generation. In this experiment, a mitochondrial fraction will be isolated from beef heart muscle. The mitochondria will be analyzed for protein content and fractionated into submitochondrial particles. Each fraction will be analyzed for malate dehydrogenase and monoamine oxidase activities. 

Fig. S.26. Summary of the potential energy released from oxidation of carbon materials to carbon dioxide and water via the tricarboxylic acid cycle and electronc transport in the...

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... 

Under aerobic conditions, the glycolytic pathway becomes the initial phase of glucose catabolism (fig. 13.2). The other three components of respiratory metabolism are the tricarboxylic acid (TCA) cycle, which is responsible for further oxidation of pyruvate, the electron-transport chain, which is required for the reoxidation of coenzyme molecules at the expense of molecular oxygen, and the oxidative phosphorylation of ADP to ATP, which is driven by a proton gradient generated in the process of electron transport. Overall, this leads to the potential formation of approximately 30 molecules of ATP per molecule of glucose in the typical eukaryotic cell. 

The components of respiratory metabolism include glycolysis, the tricarboxylic acid (TCA) cycle, the electron-transport chain, and the oxidative phosphorylation of ADP to ATP. Glycolysis converts glucose to pyruvate the TCA cycle fully oxidizes the pyruvate (by means of acetyl-CoA) to C02 by transferring electrons stepwise to... 

Whereas a major function of biological membranes is to maintain the status quo by preventing loss of vital materials and entry of harmful substances, membranes must also engage in selective transport processes. Living cells depend on an influx of phosphate and other ions, and of nutrients such as carbohydrates and amino acids. They extrude certain ions, such as Na+, and rid themselves of metabolic end products. How do these ionic or polar species traverse the phospholipid bilayer of the plasma membrane How do pyruvate, malate, the tricarboxylic acid citrate and even ATP move between the cytosol and the mitochondrial matrix (see figs. 13.15 and 14.1) The answer is that biological membranes contain proteins that act as specific transporters, or permeases. These proteins behave much like conventional enzymes They bind substrates and they release products. Their primary function, however, is not to catalyze chemical reactions but to move materials from one side of a membrane to the other. In this section we discuss the general features of membrane transport and examine the structures and activities of several transport proteins. 

We now explore the remarkable process by which a long-chain saturated fatty acid is converted into two-carbon units (acetate), which can be oxidized to C02 and H20 via the tricarboxylic acid cycle and the electron-transport chain. Fatty acids that enter cells are activated to their CoA derivatives by the enzyme acyl-CoA ligase and transported into the mitochondria for /3 oxidation as we discuss later in this chapter. 

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