Gluconeogenesis Overview

Gluconeogenesis Overview

• Gluconeogenesis is the process of producing glucose from non-carbohydrate precursors.
• This process is essential when dietary glucose is insufficient.
• Specific tissues, such as the brain, red blood cells, and exercising muscles, require a constant supply of glucose.

Function of Gluconeogenesis

• Gluconeogenesis produces glucose when dietary or circulating glucose levels are insufficient for tissue needs
• This happens during starvation, prolonged fasting, or abnormal glucose homeostasis.

Sources of Glucose

• Food
• Stored glycogen
• Non-carbohydrate sources (e.g., glycerol, lactate, amino acids)

Need for Glucose

• Energy: While not the only source, glucose is the preferred source for some tissues (e.g., brain)
• Synthesis of ribose for nucleotide production: (e.g., DNA/RNA)
• Synthesis of glycoproteins and glycolipids.

When Gluconeogenesis Occurs

• When blood glucose levels drop too low to maintain cell/tissue demands.

Substrates for Gluconeogenesis

• Glycerol: Derived from triglycerides. The liver phosphorylates glycerol to glycerol-3-phosphate. It's then oxidized to dihydroxyacetone phosphate, an intermediate in glycolysis. This traps the glycerol molecule within the cell.
• Lactate: Derived from anaerobic glycolysis (e.g., exercising muscle). Lactate is transported to the liver and eventually converted back to glucose—part of the Cori cycle.
• Amino acids: Especially alanine, derived from protein breakdown. Catabolism produces α-keto acids like α-ketoglutarate, creating oxaloacetate—a crucial precursor to phosphoenolpyruvate.

Glycolysis vs. Gluconeogenesis

• Glycolysis and gluconeogenesis are not simply reverse processes.
• Gluconeogenesis uses unique steps to bypass the three irreversible steps of glycolysis.

Pyruvate to Phosphoenolpyruvate

• Pyruvate carboxylase converts pyruvate to oxaloacetate.
• Oxaloacetate is decarboxylated and phosphorylated by PEP carboxykinase to form phosphoenolpyruvate..

Conversion of PEP to Fructose 1,6-Bisphosphate

• The reactions involved reverse the direction of glycolysis.

Dephosphorylation of Fructose 1,6-Bisphosphate

• Fructose 1,6-bisphosphatase hydrolyzes fructose 1,6-bisphosphate bypassing the PFK-1 step in glycolysis.
• This step is hormonally regulated (e.g., high AMP, low insulin/high glucagon ratios).

Dephosphorylation of Glucose 6-Phosphate

• Glucose 6-phosphatase removes the phosphate group from glucose 6-phosphate, producing free glucose.
• The liver and kidneys are the only organs capable of this process

Regulation of Gluconeogenesis

• Glucagon plays a crucial role, influencing allosteric effectors and enzyme activity (e.g., phosphorylation of key enzymes).
• Substrate availability (e.g., amino acids, glycerol) also impacts the rate of gluconeogenesis.
• Hormonal regulation (e.g., insulin/glucagon ratio) has a significant effect.

This quiz explores the process of gluconeogenesis, which is the production of glucose from non-carbohydrate sources. It highlights the importance of this metabolic pathway during times of dietary insufficiency and examines the various sources and needs for glucose in the body. Test your understanding of when and why gluconeogenesis occurs.