Question

1. Bypassing the pyruvate kinase reaction. Gluconeogenesis and glycolysis are opposing pathways that share seven enzymes. The exergonic steps in glycolysis cannot be simply reversed because that would be too energetically costly. Thus, these steps are "bypassed" in gluconeogenesis with a separate set of enzymes.

a. Explain why the reaction catalyzed by pyruvate kinase is energetically favorable and essentially irreversible in the cells.

b.Explain how the cells that run gluconeogenesis are able to bypass this step with specific reactions that are also exergonic and irreversible.

Answer 1

1. Bypassing the pyruvate kinase reaction. Gluconeogenesis and glycolysis are opposing pathways that share seven enzymes. The exergonic steps in glycolysis cannot be simply reversed because that would be too energetically costly. Thus, these steps are "bypassed" in gluconeogenesis with a separate set of enzymes.

a. Explain why the reaction catalyzed by pyruvate kinase is energetically favorable and essentially irreversible in the cells.

Answer:  The  irreversible transfer of phosphate from phosphoenolpyruvate(PEP) to adenosine diphosphate (ADP) yielding one molecule of pyruvate and one molecule of ATP, is catalysed by enzyme pyruvate kinase. The phosphorylation of ADP makes the pathway energetically favourable ( PEP higher in energy then ATP, exergonic reaction with stablilty of the product) and irreversible in the cells.

Higher  regulated step  because pyruvate is a crucial intermediate building block for further metabolic pathways like  TCA( Kreb's cycle) cycle for further production of ATP under aerobic conditions, or conversion  into lactic acid or ethanol under anaerobic conditions.

b.Explain how the cells that run gluconeogenesis are able to bypass this step with specific reactions that are also exergonic and irreversible.

Answer: Gluconeogenesis pathway is the reverse of glycolysis. And conversion of puruvate to phosphoenol pathway( PEP) will be energetically too costly so it needs to be bypasses with specific reactions.

1) Pyruvate to PEP: Pyruvate synthesized by glycolysis, in the mitochondria is  first converted to 4-C oxaloacetate( supplying 1 carbon by CO2 to puruvate) by the enzyme pyruvate carboxylase. The reaction is coupled to ATP hydrolysis.

2) Oxaloacetate is shuttled out to the cytoplasm and converted to PEP( phosphoenol puruvate) by the enzyme PEP carboxykinase. CO2 is removed and energy in the form of 2 GTP high energy molecules are  utilized with a total free energy change( $\Delta$ G- 62 kJ/mol) are used up for the formation of PEP. These reactions are also hence exergonic and irreversible.