L8 - Gluconeogenesis Flashcards
Feb. 11, 2019
During what situations is gluconeogenesis active?
Fasting, or fight/flight situations
What percentage of gluconeogenesis is performed by the liver and the kidney? How does this change during prolonged starvation?
Normally 90% liver and 10% in kidneys; during prolonged starvation this changes to 60/40.
Where are most GNG enzymes found?
In the cytosol.
Three of the enzymes in GNG are found outside of the cytosol. What are these enzymes and where are they found?
Glucose 6-phosphatase (in smooth ER membrane) Pyruvate carboxylase (mitochondria) PEP carboxykinase (mitochondria and cytosol)
Which GNG enzyme bypasses glucokinase?
glucose 6-phosphatase
Which GNG enzyme bypasses PFK-1?
Fructose 1,6-bisphosphatase
Which two GNG enzymes bypass pyruvate kinase?
pyruvate carboxylase and PEP carboxykinase
GNG and glycolysis both take place in the liver; however, they do not predominate in the same cells. Which cells does GNG predominate in? Which cells does glycolysis predominate in?
GNG - periportal cells
glycolysis - perivenous cells
Pyruvate carboxylase catalyzes the conversion of what?
Pyruvate to oxaloacetate
PEP carboxykinase catalyzes the conversion of what?
Oxaloacetate to PEP
Fructose 1,6-bisphosphatase catalyzes the reaction of what?
fructose 1,6-bisphosphate to fructose 6-phosphate
Glucose 6-phosphatase catalyzes which reaction of GNG?
Last reaction: G6P to glucose
How does acetyl CoA figure into GNG? Where does it come from in gluconeogenesis?
Allosteric activator of pyruvate carboxylase. Comes from beta-oxidation
What are the two functional domains of the bifunctional enzyme PFK-2?
1) PFK-2
2) FBPase-2
What are the three starting substrates that can form glucose in GNG? And where do they come from?
1) amino acids, alanine and glutamine
2) lactate, from Cori cycle
3) glycerol, from TAG degradation
What is the glucose-alanine cycle? What does it provide and what does it start with?
The glucose-alanine cycle starts with alanine from muscle proteolysis, and returns glucose to the muscles by GNG in the liver (converts alanine to glucose)
What is the Cori cycle? Where does it take place? What is its purpose?
The Cori cycle takes lactate from muscle and turns it into glucose through hepatic GNG to provide glucose for muscles in anaerobic conditions
What enzyme turns pyruvate into alanine?
Alanine aminotransferase (ALT)
Alanine aminotransferase uses which two amino acids as cosubstrates?
1) alpha-ketoglutarate
2) glutamate
Where is pyruvate carboxylase found? What are its cofactors/cosubstrates?
1) mitochondria
2) biotin, CO2, ATP, and pyruvate
Where is PEP carboxykinase found? What reaction does it catalyze? How does the reactant get to the cytosol from the mitochondrion?
1) cytosol
2) OAA to PEP
3) malate shuttle
What is special about PEP carboxykinase?
It uses GTP instead of ATP
What enzyme is deficient in Von Gierke disease? What is another name for this disease? What metabolic process can not be performed?
1) glucose 6-phosphatase
2) glycogen storage disease, type 1
3) gluconeogenesis
Which two molecules inhibit fructose 1,6 bisphosphatase?
1) AMP
2) fructose 2,6-bisphosphate
The bifunctional enzyme PFK-2/FBPase-2 can be phosphorylated/dephosphorylated. Which domain is the phosphate removed/put on? Which molecule stimulates phosphorylation? Which dephosphorylation?
1) PFK-2
2) Glucagon stimulates dephosphorylation which INHIBITS PFK-2 and stimulates FBPase-2
3) Insulin stimulates phosphorylation which ACTIVATES PFK-2 and inhibits FBPase-2
What are the energy requirements for GNG?
4 ATP, 2 GTP, and 2 NADH
The liver can perform both GNG and this metabolic process simultaneously.
beta-oxidation
