2. The precise biochemical mechanisms underlying the rapid shutdown of glycolysis in skeletal muscle upon termination of muscle contraction have remained poorly understood for many decades. It is known that glycolytic flux declines after exercise even though Pi, ADP, and AMP remain high; however, while these adenosine-5'- nucleotides are allosteric activators of phosphofructokinase-1 (PFK-1), this enzyme remains of low ac- tivity despite their presence. The diagrams (A and B) on the right illustrate the increase in the concentrations of glycolytic in- termediates downstream of PFK-1 during exercise for 60 sec followed by the abrupt decline in their concentrations upon ces- sation of muscle contraction. Diagram C shows changes in the concentrations of phosphate metabolites pre- and post-exer- cise. A. Summed concentration of glycolytic intermediates down- stream of PFK-1 (F1,6P2 + DHAP + G3P + GAP + 1,3BPG + 3PG + 2PG + PEP; G3P, glycerol-3-phosphate). B: PFK-1 flux (grey) and the PGK + PK flux (black). C. Changes in concentrations of ATP, hexose phosphates (HP), and phosphocreatine (PCr) (C1) pre- and (C2) post- exercise measured by P-31 NMR. (a) ( 6) Write the reactions for the payoff phase of gly- colysis under anaerobic conditions. Use structural formulas, name all intermediates, enzymes, and cofactors, and indi- cate whether the reaction is readily reversible or not reversi- ble. HP intermediates 2 1.5 A 1.5 1 1 0.5 0.5 PFK1 flux (grey line) and PGK+PYK (black line) flux (mM/s) sum of glycolytic downstream of PFK1 (mM) 2 PCr B 40 55 60 65 70 75 80 80 time (s) 120 160 3 2 40 95 60 65 70 75 80 55 80 time (s) 120 160 C₁1 ATP HP Pi PCr ATP C2 T 10 5 0 -5 -10 10 5 -5 -10 ppm ppm Question #2, continued: (b) ( ) During periods of active contraction of skeletal muscle, ATP is synthesized by the action of creatine kinase. This is especially the case when ATP is not generated fast enough through oxidative phosphorylation. Write the reaction catalyzed by creatine kinase in the direction of ATP synthesis, nam- ing reactants and products and using structural formulas. (c) ( ) On the basis of the diagrams A - C above, what factor or condition underlies the down- regulation of phosphofructokinase-1 (PFK-1)? Justify your answer on the basis of the data in diagrams A - C.

2. The precise biochemical mechanisms underlying the rapid shutdown of glycolysis in skeletal muscle upon termination of muscle contraction have remained poorly understood for many decades. It is known that glycolytic flux declines after exercise even though Pi, ADP, and AMP remain high; however, while these adenosine-5'- nucleotides are allosteric activators of phosphofructokinase-1 (PFK-1), this enzyme remains of low ac- tivity despite their presence. The diagrams (A and B) on the right illustrate the increase in the concentrations of glycolytic in- termediates downstream of PFK-1 during exercise for 60 sec followed by the abrupt decline in their concentrations upon ces- sation of muscle contraction. Diagram C shows changes in the concentrations of phosphate metabolites pre- and post-exer- cise. A. Summed concentration of glycolytic intermediates down- stream of PFK-1 (F1,6P2 + DHAP + G3P + GAP + 1,3BPG + 3PG + 2PG + PEP; G3P, glycerol-3-phosphate). B: PFK-1 flux (grey) and the PGK + PK flux (black). C. Changes in concentrations of ATP, hexose phosphates (HP), and phosphocreatine (PCr) (C1) pre- and (C2) post- exercise measured by P-31 NMR. (a) ( 6) Write the reactions for the payoff phase of gly- colysis under anaerobic conditions. Use structural formulas, name all intermediates, enzymes, and cofactors, and indi- cate whether the reaction is readily reversible or not reversi- ble. HP intermediates 2 1.5 A 1.5 1 1 0.5 0.5 PFK1 flux (grey line) and PGK+PYK (black line) flux (mM/s) sum of glycolytic downstream of PFK1 (mM) 2 PCr B 40 55 60 65 70 75 80 80 time (s) 120 160 3 2 40 95 60 65 70 75 80 55 80 time (s) 120 160 C₁1 ATP HP Pi PCr ATP C2 T 10 5 0 -5 -10 10 5 -5 -10 ppm ppm Question #2, continued: (b) ( ) During periods of active contraction of skeletal muscle, ATP is synthesized by the action of creatine kinase. This is especially the case when ATP is not generated fast enough through oxidative phosphorylation. Write the reaction catalyzed by creatine kinase in the direction of ATP synthesis, nam- ing reactants and products and using structural formulas. (c) ( ) On the basis of the diagrams A - C above, what factor or condition underlies the down- regulation of phosphofructokinase-1 (PFK-1)? Justify your answer on the basis of the data in diagrams A - C.

Biochemistry

6th Edition

ISBN:9781305577206

Author:Reginald H. Garrett, Charles M. Grisham

Publisher:Reginald H. Garrett, Charles M. Grisham

Chapter27: Metabolic Integration And Organ Specialization

Section: Chapter Questions

Problem 3P

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