Lecture 21, Gluconeogenesis (Zaidi) Flashcards
Why is maintaining the level of glucose important?
Brain depends on glucose as its primary fuel and RBC use glucose as their only fuel
How much glucose does the body need per day?
160 g
How much glucose does the brain require?
120 g
How much glucose is present in body fluids?
20 g
How much glucose is readily available from glycogen?
190 g
T or F: Direct glucose reserves are sufficient enough to meet the body’s glucose needs for about a day.
True.
When is gluconeogenesis especially important?
During a longer period of fasting or starvation
Where does gluconeogenesis occur?
In liver and kidney
T or F: Gluconeogenesis is simply a reversal of glycolysis.
False. The pathway is not a reversal of glycolysis.
What does gluconeogenesis convert?
Pyruvate into glucose
What are the major precursors in gluconeogenesis?
Lactate, amino acids, and glycerol
How does gluconeogenesis bypass the irreversible steps of glycolysis?
4 enzymes that aren’t present in glycolysis
List the 4 enzymes that are present in gluconeogenesis but not glycolysis.
Pyruvate carboxylase, phosphoenolpyruate carboxykinase, fructose 1,6-bisphosphatase, glucose 6-phosphate
What is the first step of gluconeogenesis?
Pyruvate is converted to oxaloacetate by pyruvate carboxylase
Pyruvate kinase (PC) is a ___ enzyme.
Mitochondrial
How is OAA transported to the cytoplasm?
Via malate shuttle
What does pyruvate carboxylase use to produce OAA?
ATP, HCO3-
What is the second step of gluconeogenesis?
Oxaloacetate is converted to PEP by phosphoenolpyruvate carboxykinase
What does phosphoenolpyruvate carboxykinase use to produce phosphoenolpyruvate?
GTP
What is the third reaction of gluconeogenesis?
Phosphoenolpyruvate is converted to 2-phosphoglycerate by enolase
T or F: Enolase uses a water to produce 2-phosphoglycerate.
True.
What enzyme converts 2-phosphoglycerate to 3-phosphoglyerate (4th reaction of gluconeogenesis)?
Phosphoglycerate mutase
What is the 5th reaction of gluconeogenesis?
3-phosphoglycerate is converted to 1,3-bisphosphoglycerate by phosphoglycerate kinase
What does phosphoglycerate kinase use to produce 1,3-bisphosphoglycerate?
ATP
What is the 6th reaction of gluconeogenesis?
1,3-bisphosphoglycerate is converted to G3P by G3P dehydrogenase
What does G3P dehydrogenase use to produce G3P?
NADH
T or F: G3P isomerase converts G3P into DHAP.
False. TPI converts DHAP to G3P and vice versa.
Which enzyme converts G3P to fructose 1,6-bisphosphate in the 8th reaction of gluconeogenesis?
Aldolase
What is the 9th reaction of gluconeogenesis?
Fructose 1,6-bisphosphatase breaks down fructose 1,6-bisphosphate to fructose 6-phosphate
What is the 10th reaction of gluconeogenesis?
F6P is isomerized to G6P by phosphoglucose isomerase
How does G6P form free glucose?
By the action of glucose 6-phosphatase
Which enzymes of the second half of gluconeogenesis use water?
Fructose 1,6-bisphosphatase, glucose 6-phosphatase
Where is glucose 6-phosphatase located?
In lumen of ER
Describe T1.
Transports glucose 6-phosphate back to ER
Describe T2.
Transports inorganic phosphate back into cytosol
Describe T3.
Transports glucose back to cytoplasm
How do gluconeogenesis and glycolysis utilize ATP?
Glycolysis generates ATP, gluconeogenesis consumes ATP
What determines whether glycolysis or gluconeogenesis will be activated?
Energy charge (ATP/ADP ratio)
Gluconeogenesis and glycolysis are ___ regulated.
Reciprocally
List the favoring conditions of glycolysis and gluconeogenesis.
Glycolysis = blood insulin concentration is high Gluconeogenesis = blood glucose concentration is low and glycogen stores are depleted
What are the positive regulators of glycolysis and gluconeogenesis?
Glycolysis = glucose, insulin, AMP, fructose 2,6-BP, fructose 1,6-BP Gluconeogenesis = glucagon, citrate, cortisol, thyroxine, acetyl CoA
What are the negative regulators of glycolysis and gluconeogenesis?
Glycolysis = glucagon, ATP, citrate, glucose 6-P, fructose 6-P, alanine Gluconeogenesis = ADP, AMP, fructose 2,6-BP
What does fructose 2,6-BP strongly stimulate and inhibit?
Stimulates phosphofructokinase, inhibits fructose 1,6-BP
Which 2 enzymes regulate the concentration of fructose 2,6-BP?
Phosphofructokinase 2 and fructose bisphosphatase 2
Describe the Cori cycle.
Lactate produced in skeletal muscle and RBC can be converted back to pyruvate in liver; Pyruvate can enter the gluconeogenic pathway and regenerate glucose
Except PC, where are the enzymes of gluconeogenesis found?
Cytoplasm