Ch 17: Gluconeogenesis

Carbon energy source for neurons and RBC

Glucose

Neuron’s energy source

Oxidative metabolism

RBC energy source

Lactic fermentation (no mitochondria)

Glycogen stores

keep glycemia constant

Glycemia

% [glucose] present in blood

Fasting

period from the moment when glucose from the diet is exhausted from the blood; both gluconeogenesis and glycogen degredation; decreasing insulin, high glucagon

Starvation

only gluconeogenesis is available, no glycogen stores; low insulin, high glucagon

Normoglycemia

blood glucose level at 5mM

Fed

dietary carbohydrates are processed in the gut to deliver glucose; high insulin, low glucagon

Gluconeogenesis

glycogen, glycerol, and amino acids to glucose in liver

Cori cycle

glycolysis fermentation (anaerobic) in muscles during intense activity produce lactate which is transported to liver to regenerate glucose via gluconeogenesis; active in conditions of fasting and starvation

Purpose of Cori Cycle

clears lactic acid to prevent buildup which causes muscle cramps

High ATP demand

muscle, kidney, brain

High rate of fermentation

kidneys and muscle; supply of oxygen will become limited

Lactate metabolism

Reactants: Lactate, NAD+

Products: Pyruvate, NADH, H+

Enzyme: LDH

Alanine metabolism

Reactants: Alanine, a-ketoglutarate

Products: Pyruvate, Glutamic acid

Enzyme: Alanine aminotransferase

Glycerol metabolism

Reactants:

Products:

Enzyme:

Step 1 (Pyruvate to PEP)

Reactants: Pyruvate, CO2, ATP

Products: Oxaloacetate, ADP, Pi

Enzyme: Pyruvate carboxylase

(Mitochondria)

Step 2 (Pyruvate to PEP)

Reactants: Oxaloacetate, NADH, H+

Products: Malate, NAD+

Enzyme: Malate dehydrogenase

(Mitochondria)

Step 3 (Pyruvate to PEP)

Reactants: Malate, NAD+

Products: Oxaloacetate, NADH, H+

Enzyme: Malate dehydrogenase

(Cytosol)

Step 4 (Pyruvate to PEP)

Reactants: Oxaloacetate, GTP

Products: PEP, GDP, CO2

Enzyme: PEP carboxykinase

Glycolytic conditions

• increase in AMP

• increase in F-2,6-bisP

• increase in insulin

• fed

Gluconeogenic conditions

• increase in ATP

• increase in citrate

• increase in acetyl-CoA

• fasting

• increase in glucagon

Main fuel to regenerate ATP

Fatty acids (high NADH/NAD+ ratio)

Why is malate favored instead of aspartate?

more NADH inside matrix than outside in cytosol, leads to high NADH/NAD+ ratio (fatty acid metabolism)

How is a futile cycle of pyruvate to PEP avoided?

pyruvate kinase is inhibited by PKA by covalent modification (phosphorylation)