Metabolism 4: Gluconeogenesis

Question 1

During overnight fast, _____ is the major source of ATP for gluconeogenesis

Answer 1

Fatty acid oxidation

Question 2

What occurs during the Cori Cycle?

Answer 2

In liver:
2 lactate + 6 ATP –> Gluconeogenesis –> Glucose

In RBCs/Skeletal m.:
Glucose from liver –> Glycolysis –> 2 lactate + 2 ATP –> lactate goes to liver

Question 3

What occurs during the Alanine Cycle?

Answer 3

In liver:
2 alanine:
–> + 4 ATP –> Ureogenesis –> Urea –> kidney
–> 2 Pyruvate + 6 ATP –> Gluconeogenesis –> Glucose

In muscle:
Glucose from liver –> Glycolysis –> 2 pyruvate –> 2 alanine

Question 4

Name the 4 enzymes of Gluconeogenesis

Answer 4

1. Pyruvate Carboxylase (pyruvate –> Oxaloacetate)
2. PEP Carboxykinase (Oxaloacetate –> PEP)
3. Fructose-1,6-bisphosphatase (F-1,6-bisP –> F-6-P)
4. Glucose-6-Phosphatase (G-6-P –> Glucose)

Question 5

What are the symptoms and causes of Pyruvate Carboxylase Deficiency?

Answer 5

Symptoms: Failure to thrive, developmental delay, recurrent seizures, metabolic acidosis

Due to: accumulation of plasma pyruvate –> lactate (by LDH) –> increased plasma lactic acid

Diagnostic: high serum alanine

Question 6

How does ethanol ingestion cause hypoglycemia?

Answer 6

Inhibits gluconeogenesis

• Ethanol Dehydrogenase increases NADH/NAD+ ratio, which promotes conversion of pyruvate –> lactate and oxaloacetate –> malate, thereby removing 2 glucogenic precursors from pool
• Increased NADH causes increased Lactate