Pathway matrix, biochemical reactions

Systems of biochemical reactions like glycolysis, the citric acid cycle, and larger and smaller sequential and cyclic sets of enzyme-catalyzed reactions present challenges to make calculations and to obtain an overview. The calculations of equilibrium compositions for these systems of reactions are different from equilibrium calculations on chemical reactions because additional constraints, which arise from the enzyme mechanisms, must be taken into account. These additional constraints are taken into account when the stoichiometric number matrix is used in the equilibrium calculation via the program equcalcrx, but they must be explicitly written out when the conservation matrix is used with the program equcalcc. The stoichiometric number matrix for a system of reactions can also be used to calculate net reactions and pathways. 

The first two reactions in the biochemical pathway that converts NFL,+ to urea (i.e., the formation of carbamoyl phosphate and citrulline) occur in the mitochondrial matrix. Subsequent reactions that convert citrulline to ornithine and urea occur in the cytosol. Both citrulline and ornithine are transported across the inner membrane by specific carriers. 

The citric acid cycle is the final pathway for the degradation of carbohydrates, amino acids, and fatty acids. The citric acid cycle occurs in the matrix of the mitochondria. It is a cyclic series of biochemical reactions that accomplishes the complete oxidation of the carbon skeletons of food molecules. 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

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