Gluconeogensis Flashcards
What is gluconeogenesis?
anabolic reversal of glycolysis; synthesis of pyruvate and other glycolytic intermediates
What tissues synthesize glucose?
liver and kidneys
What tissues use glucose as their primary energy source?
Brain and nervous tissues, muscle, erythrocytes, testes
How are glycolysis and gluconeogenesis reciprocally regulated?
-glycogen degredegation is ON when cell needed NADH + H+ and ATP and OFF when the cell has ample NADH, H+, and ATP
-glycogen storage is ON when the cell has ample NADH, H+, and ATP (save glucose for another day), and OFF when the cell has ample NADH, H+, and ATP
Where are glucose units stored?
liver
What trigger gluconeogenesis?
-no influx of glucose
-glycogen stores are depleted in the muscles and liver
-glucose needed badly
BASICALLY: starvation conditions, not enough energy
What are the four major sources of carbon for glucose synthesis ?
LATO (lactate, amino acids, triglycerides (glycerol), cO2)
What enzymes in gluconeogenesis corespond to the glycolytic enzyme pyruvate kinase?
pyruvate carboxylase and phophoenolpyruvate carboxykinase
What enzyme in gluconeogensis correspond to the glycolytic enzyme phosphofructokinase-1?
fructose-1,6-bisphophotase
What enzyme in gluconeogenesis corresponds to the glycolytic enzyme phosphofructokinase-1?
fructose-1.6-bisphosphotase
What enzyme in gluconeogenesis corresponds to the glycolytic enzyme hexokinase?
glucose-6-phosphotase
What enzymes catalyzes the interconversion of pyruvate to phosphoenolpyruvate?
pyruvatecarboxylase and phosphoenolpyruvate carboxykinase
Reaction for pyruvate carboxylase
pyruvate + ATP + HCO3 –> oxaloacetate (beta-keto acid) + ADP + inorganic phosphate
Reaction for phosphoenolpyruvate carboxykinase
oxaloacetate + GTP –> phosphoenolpyruvate + GDP + CO2
-GTP dependent
-decarboxylation reaction
What B vitamin is required for pyruvate carboxylase?
biotin
transfers a CO2 group onto biotin to for a carboxybiotin intermediate, the CO2 from the intermediate is added to pyruvate to get oxaloacetate
What is lactate role in gluconeogenesis?
it provides carbons for gluconeogenesis; lactate is converted to pyruvate by lactate dehydrogenase where it goes to start gluneogensis in the mitochondria
Reaction for fructose-1,6-bisphosphotase
Fructose-1,6-BP + H20 –> fructose-6-P + Pi
-accompanied by the hydrolysis of water to release inorganic phosphate
-bypass reaction
Reaction for glucose-6-phosphotase
G6P + H2O –> glucose and inorganic phosphate
-accompanied by the hydrolysis of water to release inorganic phosphate
-bypass reaction
What do RBCs do in glycolytic pathway?
they synthesize and degrade 2,3-BPG as a detour from glycolytic pathway
What happens if pyruvate kinase is mutated?
-BPG increases
-more T state
-lower affinity for O2 and increased p50
**all intermediates in stage 2 of glycolysis would accumulate (including BPG)
What would happen if hexokinase was mutated?
-BPG decreases
-more R state
-higher affinity for O2 and decreased P5-
**no glycolytic intermediates would accmulate
Why is glycogen stored in long chains rather than as individual molecules in the cell?
if all glucose was stored as individual glucose, Glc would approach molar quantities (would lead to bulk H2O movement)
-it prevents cells from lysing (osmoregulator problems) because storing as a long polymer reduces EFFECTIVE concentration
Describe the structure of glycolysis?
long chain of glucose linked by alpha 1,4 glycosidic linkages
**branches of glucose links by alpha 1,6 glycosidic linkages
What are main enzymes associated with glycogen synthesis?
hexokinase, phosphoglucomutase, UDP-glucose phyrophorylase, glycogen synthase, branching enzyme, (nucleoside diphosphate kinase-indirect)
Reaction for glycogen synthase
glucose(n) –> glucose (n-1) + G1P
-removes glucose units in a repetitive process until it reaches the 4th glucose unit from branch point
How are glucose units removed ?
glycogen phosphorylase with PLP coenzyme has a phosphate that plucks off an H, from there the inorganic phosphate breaks the alpha 1,4 linkage between glucose units
What happens to the GP1 from glycogen in glycogen breakdown?
phosphoglucomutase converts to GP1–>G6P through a G-1,6-BP intermediate (adds phosphate from inorganic phosphate
-**NEAR EQ
What enzymes are associated with glycogen degradation?
-glycogen phosphorylase
-phosphoglucosemutase
-glucose 6 phosphotase (from gluconeogenesis)
-glycogen debranching enzyme
How many ATP are produced if glucose from blood goes through glycolysis?
2
How many ATP are produced if glucose unit comes from glycogen in G1P through glycolysis?
net 3
Glycogen debranching enzyme
hydrolyze alpha 1,4 transfer and synthsize alpha 1,4
What is a kind of enzyme is a the debranching enzyme?
transferase and hydrolase
What are the three reactions of debranching enzyme?
- Hydrolyze alpha 1,4 glycosidic linkage delta G=+15.5 kj/mol
- transfer branch and make alpha 1,4 glycosidic linkage delta G=-15.5 kj/mol
- hydrolyze last alpha 1,6 glycosidic linkage delta G= -7.1 kj/mol
What common enzyme do glycogen synthesis and breakdown share?
hexokinase
What is the path of glycogen breakdown in the liver?
glycogen -> G1P -> G6P -> free Glucose -> to blood
What is the path of glycogen breakdown in the muscle cells?
glycogen -> G1P -> G6P -> to glycolysis
