Gluconeogenesis Flashcards
What is Gluconeogenesis
Anabolic pathway converting pyruvate to glucose
Where does it occur?
Occurs partially in mitochondria and partially in cytoplasm of liver and kidneys
Is Gluconeogenesis simple reversal of glycolysis?
No, since need to work around the irreversible steps of glycolysis
How many rxns in Gluconeogenesis are reversible?
7 glycolytic rxns are reversible, 3 are not
Substrates for Gluconeogenesis
Include all intermediates of glycolysis and TCA cycle
The Cori Cycle
Lactate produced in muscle and RBC is used by liver to produce glucose
Most important substrates?
- Glycerol- breakdown of lipids
- Lactate- released into blood from red blood cells and excercising muscles (Cori cycle)
- Amino Acids- released from breakdown of proteins and converted into a-keto acids during amino acid metabolism
How is Pyruvate converted to oxaloacetate?
- Pyruvate carboxylase uses biotin as an activated CO2 carrier
- Biotin is cov. attached prosthetic group to enzyme
Reactions unique to Gluconeogenesis?
- Conversion of pyruvate to oxaloacetate
- Formation of phosphoenolpyruvate
- Desphosphorylation of fructose 1,6-BP
- Dephosphorylation of glucose 6-P
How many rxns req. to bypass irreversible steps?
4 rxns
Step1- Conversion of Pyruvate to Oxaloacetate
- occurs in mitochondria
- CO2 is added to pyruvate to form oxaloacetate
- Req. energy in the form of ATP
- Key regulatory step; activated by acetyl-CoA
Step 2- Transport of oxaloacetate to the cytoplasm
- oxaloacetate is shuttled to cytoplasm and then converted to PEP
- this rxn uses GTP as energy/phosphate donor
3- Dephosphorylation of Fructose 1,6-BP
- Fructose 1,6-BP catalyzes this step
- allosteric regulatory enzyme (PFK-1 counterpart)
Where does conversion of fructose 6-phosphate converted to glucose 6-phosphate occur?
Occurs in all tissues but liver gluconeogenesis stops here
4- Dephosphorylation of Glucose
- Glucose 6-P transferred to lumen of ER (in liver/kidney cells)
- GLucose 6-P hydrolyzed to Glucose by glucose 6-P
Reactant/Product of Gluconeogenesis
- 4 ATP and 2 GTP required
- Produces 1 molecules of glucose from 2 pyruvate
Regulation of Gluconeogenesis is reciprocal to glycolysis
- molecule that activates glycolysis, inhibits gluconeogenesis
Synthesis of Fructose 2,6-BP
PFK-2/FBP2 as two catalytic domains
1. PFK-2 domain= kinase domain-adds P
2. FBPase2 domain= phosphatase domain- removes P
(when 1 domain is active the other is inactive)
Kinase domain phosphorylates fructose 6-P to form fructose 2,6-BP
This is a potent activator of PFK/glycolysis (inhibit gluconeogenesis)
FBPase2 domain removes P from fructose 2,6-BP to form fructose 6-P
This inhibits glycolysis and activates gluconeogenesis
When blood glucose is low, PFK-2 is phosphorylated and inhibited
Glucagon stimulates PKA when blood glucose is scarce. FBPase 2 is activated
- glycolysis inhibited
- gluconeogenesis activated
When glucose is high, PFK-2 is dephosphorylated activating it
- high levels of fructose 6-P stimulate phosphoprotein phosphatase
- glycolysis is stimulated
- gluconeogenesis is inhibited
