Tricarboxylic acid cycle localization

A recent investigation of the current model for the tricarboxylic acid cycle in Dictyostelium discoideum may be viewed as a case study that illustrates the uses of local representation within the Power-Law Formalism (Shiraishi and Savageau, 1992a,b,c,d 1993). First, it demonstrates that systemic analysis is a powerful tool to evaluate the quality of biochemical models especially those representing the function of a complex system in vivo. Second, it demonstrates that systemic analysis allows one to diagnose deficiencies and to predict modifications that are likely to improve the model. 

The oxidation reactions involved are catalyzed by a series of nicotinamide adenine dinucleotide (NAD+) or flavin adenine dinucleotide (FAD) dependent dehydrogenases in the highly conserved metabolic pathways of glycolysis, fatty acid oxidation and the tricarboxylic acid cycle, the latter two of which are localized to the mitochondrion, as is the bulk of coupled ATP synthesis. Reoxidation of the reduced cofactors (NADH and FADH2) requires molecular oxygen and is carried out by protein complexes integral to the inner mitochondrial membrane, collectively known as the respiratory, electron transport, or cytochrome, chain. Ubiquinone (UQ), and the small soluble protein cytochrome c, act as carriers of electrons between the complexes (Fig. 13.1.1). 

Tricarboxylic acid (TCA) cycle. The cyclical process whereby acetate is completely oxidized to C02 and water, and electrons are transferred to NAD+ and flavine. The TCA cycle is localized to the mitochondria in... 

Thiamine is required by the body as the pyrophosphate (TPP) in two general types of reaction, the oxidative decarboxylation of a keto acids catalyzed by dehydrogenase complexes and the formation of a-ketols (ketoses) as catalyzed by transketolase, and as the triphosphate (TTP) within the nervous system. TPP functions as the Mg -coordinated coenzyme for so-called active aldehyde transfers in mul-tienzyme dehydrogenase complexes that affect decarboxyia-tive conversion of a-keto (2 oxo) acids to acyl-coenzyme A (acyl-CoA) derivatives, such as pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. These are often localized in the mitochondria, where efficient use in the Krebs tricarboxylic acid (citric acid) cycle follows. 

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