Question

How are glycolysis and gluconeogenesis are reciprocally regulated in the liver? Answer this question by providing explanations on all levels of pathway regulation. Discuss the reciprocal/opposite regulation in the categories shown in the following sections. However, this is not just a listing of the regulated enzymes and conditions or substances which are effectors of those reactions; you need to address types of regulation which are examples of reciprocal or opposite regulation of the two pathways.

Identify the most highly regulated steps of these pathways. Give the full reactions including reactants, produces and enzymes. For each identify the most highly regulated step AND other reactions which are regulated.  

What does “opposite” or “reciprocal” regulation of opposite pathways mean?

Discuss how reciprocal/opposite “allosteric” regulation of the most highly regulated steps of these two pathways.

Discuss the reciprocal/opposite “hormonal” regulation of the most highly regulated steps of these two pathways.

Discuss the reciprocal/opposite “reversible covalent modification” of these two pathways.

Discuss any other recipocal/opposite type of regulation that occurs in the regulation of these two pathways of glucose metabolism.

Answer 1

By reversible covalent modification-

Glucagon and epinephrine that are responsive to a decrease in blood glucose level inhibit glycolysis and stimulates gluconeogenesis in the liver by increasing concentration of cAMP. This, in turn, activates cAMP-dependent protein kinase leading to the phosphorylation and inactivation of mainly two enzymes-

1. Pyruvate kinase- It's activated form is dephosphorylated and its inactive form is phosphorylated. Insulin activates this enzyme by causing dephosphorylation through stimulating phosphatase enzyme while glucagon inactivates this enzyme by bringing about c AMP mediated phosphorylation. In the inhibited state of pyruvate kinase phosphoenolpyruvate is channelled towards glucose production.

The second enzyme to be affected by phosphorylation cascade is phosphofructokinase 2 that is inactivated but fructose 2,6 bisphosphate is reduced. PFK-`1 gets inhibited but FBPase gets stimulated. Thus when glucose is abundant as during fed state glycolysis is stimulated and when glucose is limiting glycolysis is inhibited

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