Compare and contrast glycolysis and gluconeogenesis by answering the following questions:

a) Which reactions are common between the two pathways? (Use enzyme names since the reactions addressed by only numbers are different for each pathway.)

b) Which reactions are unique to glycolysis, and which are unique to gluconeogenesis? (Identify by enzyme names.)

c) Explain in biochemical terms why the glycolytic pathway cannot just be simply reversed to achieve glucose synthesis. (Provide two reasons.)

b) Unique to glycolysis: Pyruvate kinase and lactate dehydrogenase. Unique to gluconeogenesis: Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and more.

Explanation:

In both glycolysis and gluconeogenesis, several enzymatic reactions are shared. These include the actions of hexokinase/glucokinase, phosphofructokinase-1, aldolase, triose phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, and enolase. These common reactions ensure the core carbon backbone is preserved as the intermediates shuttle back and forth between glucose breakdown and synthesis.

Distinctive to glycolysis are the irreversible reactions catalyzed by pyruvate kinase and lactate dehydrogenase. In contrast, gluconeogenesis possesses unique enzymes and reactions that facilitate the synthesis of glucose from pyruvate, such as pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. These enzymes enable gluconeogenesis to circumvent the irreversible steps of glycolysis and ultimately generate glucose.

Glycolysis cannot be directly reversed to achieve glucose synthesis due to two main reasons. Firstly, the reactions catalyzed by phosphofructokinase-1 and pyruvate kinase in glycolysis are highly exergonic and irreversible, requiring a substantial input of energy to proceed in the reverse direction. Secondly, bypass reactions in gluconeogenesis are necessary to bypass these high-energy barriers and convert pyruvate into glucose, highlighting the need for additional enzymes and steps. This ensures that glucose synthesis is energetically favorable and distinct from the glucose breakdown pathway.

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