Gluconeogenesis

Question 0

Liver and GneoG

Answer 0

Glycogen breakdown happens initially during fasting. Glycogen to glu-6-P to glucose
Gluconeogenesis turned on when glycogen levels are low. Inhibit PFK and turn on the opposite enzyme, F-1,6-pase
Liver pulls out oxaloacetate of the CAC and makes glu-6-P
Muscle aa carbon skeletons shipped to liver and conveyed to OAA
Glycerol can be used to make new glucose

Question 1

Pyruvate is major player in GneoG

Answer 1

Most carbon skeletons for gluconeogenesis arrive at the liver as pyruvate

Sources of pyruvate: lactate from amplified glycolysis ( rbcs, exercising muscle), amino acids from exercising muscle, amino acids mobilized during fasting and starvation, glycerol mobilized dring fasting and starvation

Question 2

Irreversible reactions in glycolysis

Answer 2

3 irreversible reactions
Gluconeogenesis is an anabolic pathway but it uses NADH
Requires 6 ATP and 2 NADH to overcome
4 key enzymes
1) pyruvate decarboxylase: makes 2 OAA from 2 pyruvate, mitochondria
Biotin is required which carries carbon dioxide
2) fructose-1,6-bis-phosphatase: reverse of PFK reaction, produces fructose-6-P.
Major control point
3) glucose-6-phosphatase: opposite of glucokinase/hexokinase, makes free glucose which is released in the blood
4) PEP carboxykinase: makes 2 PEP from OAA , driven by GTP and hydrolysis

Question 3

Location of GneoG

Answer 3

Only can occur in cells with mito
Primarily in live and kidney, not muscle and adipose bc they don’t have fructose-1,6-phosphatase or glucose-6-phosphatase

Question 4

Regulation of glycolysis and gluconeogenesis

Answer 4

Reciprocal regulation
PFK committed step of glycolysis, FBP of gluconeogenesis
Energy rich signals inhibit glycolysis and activate gluconeogenesis
Such as ATP, citrate and NADH
Fructose-2,6-bis-phosphatase activates glycolysis and turns off gluconeogenesis

Question 5

Fructose-2,6-bis-phosphatase

Answer 5

Stimulates glycolysis, PFK
Inhibits gluconeogenesis, FBP
- insulin increases F-2,6-bis-P in liver, PFK (glycolysis) is on and FBP (gluconeogenesis) is off
- glucagon decreases F-2,6-bis-P in liver. FBP (gluconeogenesis) is on and PFK (glycolysis) is off
- epinephrine (aroused state) decreases F-2,6-bis-P levels in liver. FBP (gluconeogenesis) is on and PFK (glycolysis) is off

Muscle–epinephrine has an opposite effect on glycolysis in muscle vs. liver. In muscle, epinephrine stimulates glycolysis to increase ATP levels. Cause an increase in F-2,6-bis-P which activates PFK and stimulates glycolysis