Gluconeogenesis Overview

Gluconeogenesis

• Gluconeogenesis is the process of synthesizing glucose from non-carbohydrate precursors
• It occurs primarily in the liver and kidneys
• Muscle proteins breakdown to supply amino acids
• These amino acids are transported to the liver and join gluconeogenesis
• Three key glycolysis reactions are essentially irreversible:
  • Hexokinase (or Glucokinase)
  • Phosphofructokinase
  • Pyruvate Kinase
• These steps must be bypassed in gluconeogenesis
• Specific enzymes are used in gluconeogenesis:
  • Pyruvate carboxylase: Catalyzes the conversion of pyruvate to oxalacetate
  • PEP carboxykinase: Catalyzes the conversion of oxalacetate to phosphoenolpyruvate
  • Fructose 1,6-bisphosphatase: Catalyzes the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate
  • Glucose 6-phosphatase: Catalyzes the conversion of glucose 6-phosphate to glucose
• The remaining gluconeogenesis reactions are catalyzed by the same enzymes as glycolysis but in the reverse direction

Gluconeogenic Precursors

• Intermediates of glycolysis: Used to synthesize glucose
• Intermediates of the citric acid cycle: Converted to oxalacetate, then to glucose
• Lactate: Lactic acid, produced from anaerobic glycolysis in cells like red blood cells (RBCs) and exercising skeletal muscles, is transported in the blood to the liver where it is converted into pyruvate, then to glucose. This process is known as the Cori cycle.
• Glycerol: Derived from lipids (triacylglycerol) in adipose tissue and converted into dihydroxyacetone phosphate (DHAP), then to glucose.
• Glucogenic amino acids: Deaminated to form α-ketoacids, which are converted to pyruvate or intermediates of the citric acid cycle, and then to glucose.

The Cori Cycle

• The Cori cycle is a metabolic pathway that involves the interconversion of glucose and lactate
• The cycle occurs between the liver and the muscles.
• In the muscles, glucose is broken down into pyruvate through glycolysis, and, under anaerobic conditions, pyruvate is converted into lactate
• The lactate is transported to the liver, where it is converted back into glucose via gluconeogenesis
• The cycle allows for the recycling of lactate
• Importance:
  • Prevents the loss of lactic acid in the urine
  • Supplies RBCs and contracting muscles with glucose for energy production

Glucogenic Amino Acids

• These are amino acids that can be converted into glucose via gluconeogenesis.
• Examples: Alanine, glycine, serine, and cysteine

Clinical Application of Gluconeogenesis

• Fructose 1,6-bisphosphatase deficiency:
  • Characterized by fasting hypoglycemia and lactic acidosis
  • Treatment: High carbohydrate diet and avoidance of fasting
• Hypoglycemia in neonates:
  • Premature babies are more susceptible to hypoglycemia due to their immature enzymes for gluconeogenesis
  • They often have low adipose tissue mass, which further exacerbates this issue.

This quiz covers the essential process of gluconeogenesis, focusing on the synthesis of glucose from non-carbohydrate precursors primarily in the liver and kidneys. Key enzymes and irreversible glycolysis reactions involved in this process are highlighted to deepen your understanding of metabolic pathways.