Biochem423 - Gluconeogenesis

Gluconeogenesis

Creating glucose from endogenous sources

Occurs primarily in the liver (and a little in the kidneys)

Glycolysis net production

+2 ATP

+2 NADH

2 Pyruvate

catabolic reaction

Gluconeogenesis net production

1 Glucose

-4 ATP

-2 GTP

-2 NADH

anabolic reaction

Different enzymes between Glycolysis and Gluconeogenesis

Glycolysis: Hexokinase (IV or II), PFK-1, Pyruvate Kinase

Gluconeogenesis: Pyruvate carboxylase, PEPCK, FBPase-1, G6Pase

Pyruvate Carboxylase

Anaplerotic reaction for TCA (creating OAA)

Converts Pyruvate to Oxaloacetate

Uses bicarbonate (HCO₃^-) and ATP (has Mg²⁺)

Upregulated by Acetyl-CoA

Phosphoenolpryuvate (PEPCK)

Oxaloacetate —> PEP

Uses GTP —> GDP + CO₂ (has Mg²⁺)

Transport of Pyruvate —> OAA —> PEP

Pyruvate carboxylase is only located in the mitochondrion

Starting material for gluconeogenesis

Oxaloacetate

All amino acids except ___ and ____ can be converted to OAA to make new glucose via gluconeogenesis (in the liver)

Leucine and Lysine — as both amino acids are ketogenic

Leucine is used to make acetyl-CoA

Lysine is used to make acetoacetyl-CoA

Cori Cycle

Using lactate produced by anaerobic respiration to make glucose

When in anaerobic conditions, pyruvate is converted into lactate (especially in skeletal muscle cells)

This lactate is sent released into the blood and collected by the liver

The liver then performs gluconeogenesis, and sends the glucose back into the bloodstream.

Redox reactions are matched up (Glucose —> Pyruvate makes NADH, and Pyruvate —> Lactate uses NADH to make NAD+)

Substrate cycles

Primary sites for reciprocal regulation of these pathways

All of these are allosteric enzymes which will be either inhibited or promoted by certain effectors

This allows substrate cycles to amplify metabolic signals for key steps

Fructose-2,6-biphosphate

F2,6BP will activate PFK-1 and inhibit FBPase-1

Bifunctional enzyme is not a part of glycolysis or gluconeogenesis, but it affects both pathways

PFK-2 activity promoted when dephosphorylated - insulin

FBAase-2 activity promoted when phosphorylated - glucagon