Metabolism | Regulation of Gluconeogenesis

Summary

This video explores the regulation of glycolysis, gluconeogenesis, and related cycles, focusing on the enzymatic control of fructose 2,6-bisphosphate. It explains how hormones like glucagon and epinephrine activate protein kinase A, which phosphorylates and regulates key enzymes such as PFK2 and fructose 2,6-bisphosphatase. The phosphorylation inhibits glycolysis and promotes gluconeogenesis, thus ensuring glucose homeostasis. The content delves into the Cory cycle and the glucose-alanine cycle, providing a clear, step-by-step explanation of these complex metabolic processes for better understanding.

Takeaways

• 😀 The enzyme PFK-2 regulates the balance between glycolysis and gluconeogenesis through its dual activities of phosphofructokinase and fructose 2,6-bisphosphatase.
• 😀 When PFK-2 is phosphorylated, its PFK-2 activity is inhibited while its fructose 2,6-bisphosphatase activity is activated.
• 😀 Fructose 2,6-bisphosphate (F2,6BP) is a key regulator of glycolysis, stimulating PFK-1 and inhibiting fructose 1,6-bisphosphatase (FBPase-1).
• 😀 A decrease in fructose 2,6-bisphosphate concentration results in the inhibition of PFK-1 and the activation of FBPase-1, promoting gluconeogenesis.
• 😀 Hormones such as glucagon, epinephrine, and norepinephrine activate protein kinase A (PKA), which leads to the phosphorylation of PFK-2 and changes in glucose metabolism.
• 😀 Phosphorylation of PFK-2 by PKA reduces the concentration of fructose 2,6-bisphosphate, inhibiting glycolysis and stimulating gluconeogenesis.
• 😀 The regulation of gluconeogenesis involves the interplay of enzymes like fructose 1,6-bisphosphatase, which is activated when fructose 2,6-bisphosphate levels drop.
• 😀 The Cori cycle involves the conversion of lactate into glucose via gluconeogenesis, maintaining blood glucose levels during anaerobic conditions.
• 😀 The glucose-alanine cycle helps transfer nitrogen to the liver for urea cycle processing while providing glucose to muscles for energy.
• 😀 The video concludes by emphasizing the importance of these regulatory cycles in maintaining energy homeostasis in the body.

Q & A

What is the role of fructose-2,6-bisphosphate in regulating glycolysis?

Fructose-2,6-bisphosphate acts as a key regulator of glycolysis by stimulating PFK-1, which is crucial for the conversion of fructose-6-phosphate into fructose-1,6-bisphosphate, thereby promoting glycolysis.

How does phosphorylation of PFK-2 affect its activity?

Phosphorylation of PFK-2 inhibits its activity, preventing the conversion of fructose-6-phosphate into fructose-2,6-bisphosphate, thus lowering the concentration of fructose-2,6-bisphosphate.

What happens when the concentration of fructose-2,6-bisphosphate decreases?

When the concentration of fructose-2,6-bisphosphate decreases, it no longer stimulates PFK-1, which inhibits glycolysis, and also relieves the inhibition of fructose-1,6-bisphosphatase, promoting gluconeogenesis.

What is the effect of glucagon and epinephrine on the enzyme complex consisting of PFK-2 and F2,6BPase?

Glucagon, epinephrine, and norepinephrine activate protein kinase A (PKA), which phosphorylates the enzyme complex, leading to the inhibition of PFK-2 and stimulation of F2,6BPase.

What is the function of fructose-1,6-bisphosphatase in gluconeogenesis?

Fructose-1,6-bisphosphatase plays a key role in gluconeogenesis by converting fructose-1,6-bisphosphate into fructose-6-phosphate, which can then be used to synthesize glucose.

How does decreased fructose-2,6-bisphosphate affect glycolysis and gluconeogenesis?

Decreased fructose-2,6-bisphosphate results in the inhibition of glycolysis (due to the reduced activation of PFK-1) and the stimulation of gluconeogenesis (by relieving the inhibition of fructose-1,6-bisphosphatase).

What is the overall effect of the phosphorylation of the PFK-2/F2,6BPase enzyme complex?

Phosphorylation of the PFK-2/F2,6BPase enzyme complex promotes gluconeogenesis by reducing the concentration of fructose-2,6-bisphosphate, which inhibits glycolysis and stimulates glucose production.

What are the signaling molecules involved in the phosphorylation of the PFK-2/F2,6BPase complex?

Glucagon, epinephrine, and norepinephrine are the key signaling molecules that activate protein kinase A (PKA), which then phosphorylates the PFK-2/F2,6BPase enzyme complex.

What happens to the concentration of fructose-6-phosphate when fructose-2,6-bisphosphate is low?

When fructose-2,6-bisphosphate is low, the activity of PFK-1 is reduced, leading to a decreased conversion of fructose-6-phosphate into fructose-1,6-bisphosphate, and inhibiting glycolysis.

What cycle and processes are covered in the video regarding the regulation of gluconeogenesis?

The video covers the regulation of gluconeogenesis, including the Cory cycle and the glucose-alanine cycle, explaining how these pathways support glucose production and regulation.