16 CAC Regulation

16 CAC Regulation - B iochemis ry E duca ion Department of...

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Unformatted text preview: B iochemis ry E duca ion Department of iochemistry & Molecular iology University of New Mexico BIOC 423 Int oducto y Biochemist y Glyoxylate Cycle and Regulation of the CAC OBJECTIVES • Understand the function and know the sub-cellular locations of the enzymes of the glyoxalate cycle. • Know which other metabolic pathways are fed by the citric acid cycle. • Understand the significance of anaplerotic reactions. • Understand the significance of the pyruvate carboxylase reaction. • Know which reactions in the citric acid cycle are regulated, which molecules regulate these reactions, the mechanism of regulation, and understand how these regulators integrate the reactions of citric acid cycle with demands for the products of the citric acid cycle. OUTLINE Metabolic role of CAC Intermediates Glucose synthesis Fatty acid synthesis Heme synthesis Amino acid synthesis Forbidden transitions Regulation of the CAC Cycle Energy charge Anaplerotic Reactions Pyruvate carboxylase Amino acid oxidation Malic enzyme - will be considered in a different context Glyoxalate cycle LECTURE Metabolic role of TCA Intermediates As stated in our previous lecture the CAC is the final destination for the oxidation of all our fuel molecules. Carbohydrates, lipids, amino acids and nucleic acids can all be metabolized into glycolytic or CAC intermediates and are then oxidized in the CAC to CO 2 and the reducing power is captured as NADH and FADH 2 . In addition to oxidation, intermediates of the CAC also serve as the starting material for the synthesis of several important biological compounds. Some of these compounds and their starting material are illustrated in the figure below. The problem develops when we consider that the matrix of the mitochondria cannot hold much mass and at any point in time we have relatively low concentrations of the CAC intermediates. What will happen if the signal is sent out to make glucose? Oxaloacetate will be used as the starting material for glucose synthesis; however, once it is gone there is no more oxaloacetate left to condense with acetyl-SCoA for the continued oxidation of acetate. The CAC would rapidly run out of intermediates and stop. The analogous argument can be made for the synthesis of each of the biological molecules indicated in the above figure. This concept is further complication with a common misunderstanding about the CAC. That wrong understanding is that 2 acetyl-SCoA molecules are used to make a new oxaloacetate. The failure of 2acetyl-SCoA molecules to make oxaloacetate or one of its precursors is the basis for the concept of biochemically forbidden transitions between biological fuel molecules. The diagram below is an attempt to illustrate that concept....
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16 CAC Regulation - B iochemis ry E duca ion Department of...

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