Glucose Synthesis

# Concept

Glucose synthesis is the process of creating glucose from intermediate products such as pyruvate, lactate, amino acids, and other oses. This process is also known as gluconeogenesis.

# Pathways of Glucose Synthesis

There are four main pathways for glucose synthesis:

• From pyruvate

• From lactate

• From amino acids

• From other oses

# Glucose Synthesis from Pyruvate

• Note: The breakdown of glucose to pyruvate has three irreversible reactions. To synthesize glucose from pyruvate, these three reactions need to be reversed.

• Three irreversible reactions in glucose breakdown:

1. Phosphoenolpyruvate → Pyruvate

2. F6P → F1,6DiP

3. G6P → Glucose

• Reversal of three irreversible reactions:

• Reaction 1:

• Lactate → Pyruvate (by LDH, using NAD+, producing NADH+H+)

• Pyruvate → Oxaloacetate (by pyruvate carboxylase, using ATP and CO2, producing ADP, Pi)

• Oxaloacetate → Phosphoenolpyruvate (by phosphoenolpyruvate carboxykinase)

• Reaction 2: F1,6DiP → F6P (by F1,6 diphosphatase)

• Reaction 3: G6P → Glucose (by glucose 6 phosphatase)

# Glucose Synthesis from Lactate

• Other names: Cori cycle, lactate cycle

• Process: Glycogen in muscles breaks down to G6P → Pyruvate → Lactate → Enters blood → Liver cells → Pyruvate → G6P → Glucose → Enters blood to provide energy for the body.

# Glucose Synthesis from Amino Acids

• Divided into three groups:

• Group 1: Amino acids that are converted to pyruvate

• Group 2: Amino acids that are converted to intermediate products of the Krebs cycle

• Group 3: Amino acids that are converted to phosphoglycerate

• List of amino acids by group:

• Group 1 (pyruvate): Threonine, glycine, serine, tryptophan, alanine, cysteine, hydroxyproline

• Group 2 (Krebs cycle intermediates): Proline, arginine, histidine, glutamic acid, glutamine, valine, isoleucine, methionine, threonine, phenylalanine, tyrosine, aspartic acid, asparagine.

• Group 3 (phosphoglycerate): Threonine, glycine, serine, hydroxyproline

# Glucose Synthesis from Oses

• Oses involved: Galactose, mannose, fructose

• Glucose synthesis from fructose:

• Fructose → F1,6DiP (fructokinase) → F6P (F16 disphosphatase) → G6P (phosphohexose isomerase) → Glucose (G6 phosphatase)

• Glucose synthesis from mannose:

• Mannose → Man.6P (hexokinase) → F6P (man.isomerase) (similar to fructose)

• Glucose synthesis from galactose:

• Galactose → Gal1P (galactose kinase) → UDP gal (gal uridyl transferase) → UDP G (epimerase) → Glycogen (glycogen synthetase) → G1P (phosphorylase) → G6P (phospho glucomutase)