Describe the role of the citric acid cycle as a central metabolic mechanism. Explain what happens to the cells’ abilities to oxidize acetyl CoA when intermediates of the cycle are drained off for amino acid biosynthesis. Glucose is a source of energy that is metabolized into glycolysis to pyruvate yielding ATP. To become more efficient, pyruvate must be oxidized into carbon dioxide and water. This combustion of carbon dioxide and water to generate ATP is called cellular respiration (Tymoczko, Berg & Stryer, 2013, p. 315). In eukaryotic cells, this aerobic process is used because of the efficiency. Cellular respiration is divided into parts: carbon fuels are completely oxidized with a concomitant generation of high transfer potential electrons in a series of reactions called citric acid cycle, tricarboxylic acid cycle, or Krebs cycle (Tymoczko, p. 318); the acetyl groups are fed into the citric cycle which are oxidized to CO2 and the energy released in conserved reduced electron carriers- NADH and FADH; the high transfer potential electrons transferred to oxygen to form water in a series of oxidation-reduction reactions called oxidative phosphorylation (Tymoczko, p. 318). The citric acid cycle takes place in the mitochondria and is the central metabolic hub in the cell; the gateway to aerobic metabolism of all fuel molecules (Tymoczko, p. 318). This cycle is important source for the building blocks of molecules such as amino acids, nucleotide bases, and porphyrin. Pyruvate can convert into different molecules depending on the aerobic (acetyl coenzyme A) or anaerobic condition (lactic acid or ethanol). In the presence of oxygen, acetyl CoA is able to enter the citric acid cycle because this is the most acceptable fuel input into the cell. The path that the pyruvate takes depends on the energy needs of the cell and the oxygen availability (Tymoczko, p. 318). Pyruvate dehydrogenase complex consist of three distinct enzymes each with its own active site: Pyruvate dehydrogenase catalyzes the decarboxylation of pyruvate and the formation of acetyllipoamide, dihydrolipoyl transacetylase forms acetyl CoA, and dihydrolipoly dehydrogenase regenerates the active transacetylase (Tymoczko, p. 319). These three enzymes participate with five coenzymes: thiamine pyrophosphate, lipoic acid, coenzyme A, NAD+, and FAD. Acetyl CoA undergoes oxidation by donating the acetyl group to the four-carbon compound oxaloacetate to form the six-carbon citrate. Citrate is transformed to isocitrate (six-carbon molecule), that is dehydrogenated with the loss of CO2 (twice) to yield a five-carbon compound a-ketoglutarate (oxoglutarate). A-ketoglutarate undergoes loss of CO2 yielding a four-carbon succinate and second molecule of CO2. Succinate is enzymatically converted into a three step four-carbon oxaloacetate. Citric acid cycle removes electrons from citrate and uses these electrons to form NADH and FADH2. These electrons carriers yield nine molecules of ATP when oxidized by O2 in oxidative phosphorylation. Electrons released in the reoxidations of NADH and FADH2 flow through a series of membrane proteins (electron-transport chain) generating a proton gradient across the membrane. This proton gradient is used to generate ATP from ADP and inorganic phosphate (Tymoczko, p. 330). The citric acid is comprised of two stages: Each turn of the cycle, one acetyl group (two-carbon) enters the acetyl-CoA and two molecules of CO2 leave-one molecule of oxaloacetate is used to form citrate then metabolized to a four carbon molecule; the remaining four carbon molecule is metabolized after many reactions- oxaloacetate is regenerated. The citric acid cycle has eight steps:
1. The formation of citrate is the condensation of acetyl-CoA with oxaloacetate to form citrate and is catalyzed by citrate synthase. This occurs by the condensation of four-carbon unit, oxaloacetate, and a two-carbon unit, the acetyl group of acetyl CoA. Oxaloacetate reacts...
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