Regulation of Gluconeogenesis Flashcards
True or false: Glycolysis and gluconeogenesis can operate simultaneously in a cell.
False; they are coordinated (through enzyme control) so that one pathways is relatively inactive while one is highly active.
What is the major control point for glycolysis? What activates it? What inhibits it?
Phosphofructokinase; ADP, AMP, and F2,6P; ATP inhibits it.
What is the flux through the PFK and FBPase cycle determined by?
Concentration of fructose-2,6-bisphosphate (F2,6P)
What is the concentration of F2,6P determined by?
Two enzymes: rate of synthesis of phosphofructokinase-2 (PFK-2) and rate of degradation of fructose bisphosphatase-2 (FBPase-2)
Fructose-2,6-bisphosphatase is an activator of ___________ and an inhibitor or ___________.
Activates phosphofructokinase; inhibits fructose 1,6-bisphosphatase (FBPase).
How does F2,6P control PFK?
When blood glucose falls, F2,6P loses a phosphoryl group to form fructose-6-phosphatase, which no longer binds to PFK, thereby stopping glycolysis.
Which enzyme phosphorylates F6P to F2,6P, thereby activating PFK?
PFK2 (phosphofructokinase 2)
Which enzyme dephosphorylates F2,6P to F6P, thereby de-activating PFK?
FBPase2 (fructose bisphosphatase 2)
True or false: Both PFK2 and FBPase2 are located on the same enzyme.
True
In which organ are the rates of glycolysis and gluconeogenesis adjusted to maintain blood glucose levels through the regulation of phosphofructokinase?
Liver
What controls when gluconeogenesis predominates over glycolysis in the liver?
Phosphorylation of a serine residue (triggered by glucagon and a resulting cAMP cascade) causes the phosphorylation of the bifunctional enzyme containing PFK2 and FBPase2. This activates FBPase2 and inhibits PFK2, lowering the level of F-2,6-BP and, therefore, allowing gluconeogenesis to predominate.
True or false: gluconeogenesis does not occur in muscle.
True
What controls when glycolysis predominates over gluconeogenesis in the liver?
When glucose levels in the blood rise, glucagon levels fall, causing the phosphoryl group to be removed from the bifunctional enzyme, thereby activating PFK2 and inhibiting FBPase2. This leads to a rise in F 2,6-BP, leading to an acceleration in glycolysis.
What is the coordinated control of glycolysis and gluconeogenesis in liver due to?
The location of the kinase and the phosphatase domains on the same chain as the regulatory domain.
What does phosphorylation of a site on the bifunctional enzyme in heart muscle do?
The reverse as in liver; it activates PFK-2 (rather than inhibiting), causing an increase in F2,6P, stimulating glycolysis.
What causes the phosphorylation of the bifunctional enzyme in heart muscle, activating PFK-2 and stimulating glycolysis?
Hormones stimulating glycogen breakdown, such as epinephrine (glycogen breakdown is coordinated with glycolysis).
Why is skeletal muscle not subject to epinephrine’s cAMP-dependent control?
It’s isoenzyme lacks phosphorylation sites.
True or false: Skeletal muscle always does glycolysis if glucose comes in from glycogen or the blood.
True; because it lacks the phosphorylation site necessary for covalent modification/control.
What happens in heart muscle if you are under stress or have low glucose levels?
Glucagon or epinephrine/norepinephrine cause glycogen breakdown to glucose and glycolysis occurs (and ATP is made).
What activates pyruvate carboxylase?
Acetyl Co-A allosterically activates it
What activates PEP carboxykinase?
There are no known allosteric activators.
In with organ is alanine an allosteric inhibitor for pyruvate kinase (thereby preventing the formation of pyruvate) in liver?
Alanine (a gluconeogenic precursor; i.e., it is converted to pyruvate through gluconeogenesis.)
How does phosphorylation affect liver pyruvate kinase?
It inactivates it.
The pathways of both ___________ and __________ flow towards glucose-6-phosphate.
gluconeogenesis and glycogen breakdown
What enzyme in glycogen breakdown is activated by phosphorylation?
Glycogen phosphorylase
What three general things affect glucose metabolism?
1) Allosteric affectors
2) Long-term changes in the amounts of enzymes synthesized.
3) Pancreatic and adrenal hormones that influence regulatory proteins.
Where is the key difference in gluconeogenesis in skeletal, heart, and liver tissue?
Glucose-6-phosphate
What inhibits transcription of the gene for PEPCK?
Insulin
How does an increase in the concentration of cAMP affect glycogen metabolism?
1) Promotes transcription of PEPCK gene, FBPase gene, and G6P gene (all of which promote gluconeogenesis).
2) Represses the transcription of Glucokinase gene, PFK gene, and PFK-2/FBPase-2 bifunctional enzyme gene.
