Transporters tricarboxylate

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). 

Figure21-4. The provision of acetyl-CoA and NADPH for lipogenesis. (PPP, pentose phosphate pathway T, tricarboxylate transporter K, a-ketoglutarate transporter P, pyruvate transporter.)...

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

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 citric acid cycle, also called the Krebs cycle or the tricarboxylic add (TCA) cyde, is in the mitochondria. Although oxygen is not directly required in the cyde, the pathway will not occur anaerobically because NADH and FADH will accumulate if oxygen is not available for the electron transport chain. 

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). 

How complex can the proteome of hydrogenosomes in T. vaginalis be expected to be Trichomonad hydrogenosomes have lost many standard metabolic capacities of mitochondria like—and consequently most of the proteins involved in—the tricarboxylic cycle, membrane-bound electron transport and ATP-production (Muller 1993), or fatty acid synthesis (Beach et al. 1990). Because of the absence of a genome (Clemens and Johnson 2000) the complex machineries of DNA replication and repair, gene transcription and protein synthesis are also absent from these organelles. On the other hand, experimental evidence exists for only a small number of metabolic... 

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). 

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