Gluconeogenesis Flashcards
What are the non-carbohydrate precursors in glucose synthesis?
- pyruvate
- lactate
- alanine
- glycerol
- propionate
What components of the body require a constant supply of glucose?
brain and erythrocytes
Where does gluconeogenesis take place?
liver (90%) and kidney (10%)
What are the 3 irreversible steps in glycolysis?
- glucose –> glucose-6- phosphate
- hexokinase
- fructose-6-phosphate –> fructose-1,6-bisphosphate
- phosphofructokinase
- phosphoenolpyruvate –> pyruvate
- pyruvate kinase
What is the first enzymatic step involved gluconeogenesis from pyruvate?
pyruvate + CO2 –> oxaloacetate + ADP + P
pyruvate carboxylase
Where is pyruvate kinase found? It requires what prosthetic group?
How is it regulated?
mitochondrial enzyme
requires biotin as prosthetic group
regulated by acetyl-CoA
How is Biotin involved in the transfer of CO2 to pyruvate to convert it to oxaloacetate?
- CO2 is covalently bound to biotin-enzyme
- ATP hydrolysis to ADP + Pi is required for this step
- Biotion serves as a carrier of activated CO2
- activated CO2 is transferred to pyruvate to form oxaloacetate
How does gluconeogenesis finish in the cytoplasm if it starts in the mitochondria & oxaloacetate is unable to cross the mitochondrial membrane?
Malate / Aspartate Shuttle
oxaloacetate is not transported across the mitochondrial inner membrane
malate dehydrogenase converts oxaloacetate to malate – malate can be transported to the cytoplasm
OR
aspartate transaminase converts oxaloacetate to aspartate – aspartate can be transported to the cytoplasm
once in the cytoplasm malate / aspartate are conveted back to oxaloacetate
What is the second enzymatic step in gluconeogenesis from pyruvate?
Oxaloacetate –> phosphopheonolpyruvate
simultaneous decarboxylation & phosphorylation: phosphoenolpyruvate carboxykinase
GTP required for reaction
What gluconeogenesis steps circumvent the pyruvate kinase step of glycolysis?
pyruvate carboxylase and phosphoenolpyruvate carboxykinase
How is PEP converted to Fru-1,6-bisphosphate during gluconeogenesis?
Where in the cell does this reaction take place?
using reversible glycolytic enzymes
cytosol
What is the third regulated step in gluconeogenesis from pyruvate?
Fru-1,6-bisphosphate –> Fru-6-phosphate
fructose-1,6-bisphosphatase
irreversible reaction
major control point
What is the function of glucose-6-phosphatase?
What is a unique characteristic about this enzyme?
glucose-6-phosphate –> glucose
irreversible reaction
expressed only in liver and kidney
ER enzyme
What is the overall energy cost of gluconeogenesis?
- pyruvate –> oxaloacetate: 2 ATP (per glucose)
- oxaloacetate –> phosphoenolpyruvate: 2 GTP
- 3-phosphoglycerate –> 1,3-bisphosphoglycerate: 2 ATP
SUM: 6 high energy phosphate bonds used per glucose produced
How is hormonal regulation of gluconeogenesis in the liver accomplished?
varying the concentrationof fructose-2,6-bisphosphate
- Fru-2,6-BP stimulates PFK1
- Fru-2,6-BP inhibits F-1,6-BPase
pyruvate kinase
- glucagon decreases PK activity
- epinephrin increases [cAMP] – effects similar to glucagon
What is the name of the cycle of lactate to the liver & glucose to the erythrocytes and muscle?
Cori cycle
What is the name for the transfer of alanine for glucose?
Where does this occur?
The alanine cycle
- Muscle
- pyruvate transaminate dto alanine & exported to blood
- Liver
- alanine & lactate converted to pyrucate and subsequently glucose
What amino acids are substrates for gluconeogenesis?
All except Leu and Lys
Glycerol is released from what process?
It enters gluconeogenesis at what step?
released from hydrolysis of triacylglycerols by adipose tissue
enters at level of DHAP
