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UPSC MainsBOTANY-PAPER-II20247 Marks
Q33.

Describe the process of gluconeogenesis and its significance.

How to Approach

This question requires a detailed understanding of gluconeogenesis, a crucial metabolic pathway. The answer should begin with a clear definition, then elaborate on the process, including the substrates, enzymes involved, regulation, and cellular locations. Finally, its physiological significance, particularly during fasting and exercise, must be highlighted. A structured approach, dividing the process into stages, will enhance clarity. Focus on the biochemical aspects and their relevance to maintaining blood glucose levels.

Model Answer

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Introduction

Gluconeogenesis, literally meaning “creation of new glucose,” is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and certain amino acids. This process is essential for maintaining blood glucose levels during periods of fasting, starvation, or intense exercise when glucose intake from the diet is insufficient. Unlike glycolysis, which breaks down glucose, gluconeogenesis builds it up. It’s primarily carried out in the liver and, to a lesser extent, in the kidneys, playing a vital role in glucose homeostasis.

The Process of Gluconeogenesis

Gluconeogenesis is not simply the reverse of glycolysis. While it shares several steps with glycolysis, three irreversible steps in glycolysis must be bypassed by different enzymes in gluconeogenesis. These bypasses are crucial and require significant energy expenditure.

1. Pyruvate to Phosphoenolpyruvate (PEP)

This is a two-step process:

  • Step 1: Pyruvate is converted to oxaloacetate (OAA) by pyruvate carboxylase, a mitochondrial enzyme. This reaction requires ATP and biotin as a cofactor.
  • Step 2: OAA is converted to PEP by phosphoenolpyruvate carboxykinase (PEPCK). This reaction occurs in both the mitochondria and the cytosol and requires GTP.

2. Fructose-1,6-bisphosphate to Fructose-6-phosphate

The irreversible step of phosphofructokinase-1 (PFK-1) in glycolysis is bypassed by fructose-1,6-bisphosphatase. This enzyme hydrolyzes fructose-1,6-bisphosphate to fructose-6-phosphate, releasing inorganic phosphate.

3. Glucose-6-phosphate to Glucose

The irreversible step of hexokinase/glucokinase in glycolysis is bypassed by glucose-6-phosphatase, an enzyme found primarily in the liver and kidneys. This enzyme hydrolyzes glucose-6-phosphate to glucose, releasing inorganic phosphate. This is the final step in gluconeogenesis.

Substrates for Gluconeogenesis

Several substrates can be used for gluconeogenesis:

  • Lactate: Produced during anaerobic glycolysis in muscles, transported to the liver via the Cori cycle.
  • Glycerol: Released from the breakdown of triglycerides in adipose tissue.
  • Amino Acids: Glucogenic amino acids (e.g., alanine, glycine, serine) can be converted to pyruvate or intermediates of the citric acid cycle.

Regulation of Gluconeogenesis

Gluconeogenesis is tightly regulated to maintain blood glucose homeostasis. Key regulatory mechanisms include:

  • Hormonal Control: Glucagon and cortisol stimulate gluconeogenesis, while insulin inhibits it.
  • Allosteric Regulation:
    • Acetyl-CoA: High levels of acetyl-CoA (indicating abundant energy) activate PEPCK.
    • AMP: High levels of AMP (indicating low energy) inhibit fructose-1,6-bisphosphatase.
  • Gene Expression: Glucagon and cortisol increase the expression of genes encoding enzymes involved in gluconeogenesis (e.g., PEPCK, glucose-6-phosphatase).

Cellular Location

Gluconeogenesis occurs primarily in the liver and, to a lesser extent, in the kidneys. The initial steps (conversion of pyruvate to OAA) take place in the mitochondria, while the remaining steps occur in the cytosol.

Glycolysis Gluconeogenesis
Glucose → Pyruvate Pyruvate → Glucose
10 steps 11 steps (bypasses 3 irreversible steps of glycolysis)
Energy producing (ATP, NADH) Energy consuming (ATP, GTP, NADH)
Occurs in cytosol Mitochondria & Cytosol

Conclusion

Gluconeogenesis is a vital metabolic pathway that ensures a constant supply of glucose, particularly during periods of fasting or increased energy demand. Its regulation is complex, involving hormonal signals and allosteric control, highlighting its importance in maintaining glucose homeostasis. Disruptions in gluconeogenesis can lead to hypoglycemia or contribute to metabolic disorders like type 2 diabetes. Understanding this pathway is crucial for comprehending overall metabolic regulation and its clinical implications.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

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Additional Resources

Key Definitions

Glucose Homeostasis
The maintenance of stable glucose concentrations in the body fluids. This is crucial for providing a constant energy supply to cells, especially the brain.
Allosteric Regulation
The regulation of an enzyme's activity by the binding of a molecule (the allosteric effector) to a site on the enzyme different from the active site, causing a conformational change that alters the enzyme's activity.

Key Statistics

Approximately 90% of gluconeogenesis occurs in the liver, with the remaining 10% taking place in the kidneys.

Source: Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 7th ed. New York: W.H. Freeman; 2017.

Approximately 60-90% of post-absorptive glucose production comes from gluconeogenesis, with the remainder from glycogenolysis.

Source: Berg JM, Tymoczko JL, Stryer L. Biochemistry. 7th ed. New York: W.H. Freeman; 2012.

Examples

Cori Cycle

During strenuous exercise, muscles produce lactate as a byproduct of anaerobic glycolysis. This lactate is transported to the liver, where it is converted back to glucose via gluconeogenesis. The glucose is then released back into the bloodstream to fuel muscle activity. This cyclical process is known as the Cori cycle.

Frequently Asked Questions

▶What happens to gluconeogenesis in individuals with type 2 diabetes?

In type 2 diabetes, gluconeogenesis is often dysregulated, leading to excessive glucose production by the liver even when blood glucose levels are already high. This contributes to hyperglycemia and insulin resistance.

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