Name the key glycolytic and gluconeogenic enzymes and how they are regulated by insulin and glucagon.

• A. Glycolysis: PFK-1; gluconeogenesis: PEPCK and pyruvate carboxylase; F2,6BP increases with insulin and decreases with glucagon; insulin favors glycolysis.
• B. Glycolysis: PK, LDH; Gluconeogenesis: G6PD; F2,6BP unaffected by hormones.
• C. Glycolysis: Hexokinase; Gluconeogenesis: Pyruvate dehydrogenase; Insulin inhibits glycolysis.
• D. Glycolysis: PFK-1; Gluconeogenesis: PEPCK and pyruvate carboxylase; F2,6BP regulated by insulin decreases and glucagon increases.

Answer: (A)

This question is about how insulin and glucagon coordinate glucose metabolism by tuning a major glycolytic checkpoint and the main gluconeogenic steps. The glycolytic enzyme at the heart of this control is PFK-1, the key rate-limiting enzyme that commits glucose to breakdown. Its activity is strongly boosted by fructose-2,6-bisphosphate (F2,6BP), a regulator produced by the bifunctional enzyme that responds to insulin and glucagon. In the fed state, insulin promotes dephosphorylation and activation of this enzyme, raising F2,6BP, which in turn activates PFK-1 and drives glycolysis. In contrast, glucagon activates the phosphorylated form of the same bifunctional enzyme, lowering F2,6BP, decreasing PFK-1 activity, and shifting metabolism away from glycolysis.

For gluconeogenesis, the main control points are pyruvate carboxylase, which converts pyruvate to oxaloacetate in mitochondria, and PEP carboxykinase (PEPCK), which converts oxaloacetate to phosphoenolpyruvate. Glucagon, signaling fasting, upregulates these enzymes via cAMP/PKA pathways to drive glucose production. Insulin counteracts this by suppressing their expression and activity, reducing hepatic gluconeogenesis.

Putting it together, the best choice identifies PFK-1 for glycolysis and PEPCK plus pyruvate carboxylase for gluconeogenesis, and the regulatory effect that insulin increases F2,6BP to promote glycolysis while glucagon lowers it to promote gluconeogenesis.