Untitled Flashcards Set

Class Notes for Gluconeogenesis

 

Recalling glycolysis:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



Net reaction of glycolysis:

 

Glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O

 

 

 

 

 

 

Gluconeogenesis is not the exact reverse of glycolysis:

Three bypass points:

                        glycolytic enzymes                             gluconeogenesis enzyme

 

  1. Hexokinase                                                     Glucose-6-phosphatase

 

  1. Phosphofructokinase-1 (PFK-1)                     Fructose-1,6-biphosphatase

 

  1. pyruvate kinase                                               a. Pyruvate carboxylase

 

                                                                                    b. Phosphoenolpyruvate carboxykinase (PEPCK)

 

 

Note:  Biosynthesis is a reductive process, thus NADPH is also needed.

 

Synthesis of phosphoenoylpyruvate, via oxaloacetate, from pyruvate/lactate





 




                                                                                                                  [compare with figure 16-20]



 

 

 

 

 

 

 

 

 

Action of pyruvate carboxylase (study page 547):

net reaction:

pyruvate +  HCO3-  + ATP  {carboxyphosphate}/{carboxybiotin} oxaloacetate +  ADP + Pi

 

requires coenzyme:   biotin  (biocytin or biotinyllysine on the enzyme)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



                                                                          think of oxaloacetate as an activated form of pyruvate

 

 

 

 

Action of PEPCK (phosphoenoylpyruvate carboxykinase)

net reaction:

oxaloacetate  +  GTP      PEP   +   GDP  +  CO2

Mechanism:

 

 

 

 

 

 

 

 

 

[Thus, the overall bypass of pyruvate kinase requires ATP and GTP to drive the reaction; ∆G’o = 0.9 kJ/mol; ∆G = -25 kJ/mol)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



Points of Regulation of Gluconeogenesis Enzyme Activity:

 

                        allosteric                     allosteric                     enzyme                                    protein

Enzyme           inhibitors                     activators                    phophorylation                        synthesis

 

PFK                 ATP, citrate                AMP, F-2,6-BP

 

FBPase            AMP, F-2,6-BP          

 

PK                   alanine                        F-1,6-BP                     inactivates

 

Pyruvate                                              acetyl CoA                 

Carboxylase

 

PEPCK                                                                                                                                    stimulated

by glucagons

 

PFK-2             Citrate                         AMP, F6P, Pi              inactivates

 

FBPase-2        F6P                              glycerol-3-P                activates

What would happen to flux through the glycolysis or gluconeogenesis pathways?

Condition

Glycolysis

Gluconeogenesis

Increase in Fructose-2,6-Bisphosphate

Increases (activates PFK-1)


 

Decreases (inhibits FBPase-1)


Increase in downstream metabolites (TCA intermediates)

Decreases (feedback inhibition)

Increases (signals need for glucose storage)

Increase in glucagon


 

Decreases (inhibits PFK-1, activates FBPase-1)


Increases (stimulates key gluconeogenic enzymes)

Increase of insulin


 

Increases (stimulates PFK-1 and glycolysis enzymes)


Decreases (inhibits gluconeogenic enzymes)

Increase in Epinephrine

Increases in muscles (prepares for energy demand)

Decreases in muscles; increases in liver (to provide glucose to blood)

low cytosolic energy state (low ATP)

Increases (stimulates glycolysis to generate ATP)

Decreases (energetically expensive)