Lecture 21/Textbook Ch. 17: Gluconeogenesis Flashcards
Gluconeogenesis
the synthesis of glucose from noncarbohydrate precursors
The major site of gluconeogenesis is the —–, with a small amount also taking place in the —–
- liver
- kidney
The gluconeogenic pathway converts —— into glucose.
pyruvate
Noncarbohydrate precursors of glucose are first converted into —– or enter the pathway at later intermediates
- pyruvate
Lactate is formed by active skeletal muscle through lactic acid fermentation when the rate of glycolysis exceeds the rate at which ——-
muscle can process pyruvate aerobically
The enzymes for gluconeogenesis are located in the —-, except for pyruvate carboxylase (in the —–) and glucose 6-phosphatase (membrane bound in the ——)
- cytoplasm
- mitochondria
- endoplasmic reticulum
Glucogenesis is the same reactions in reverse compared to glycolysis except the 3 irreversible reactions (3):
- Pyruvate carboxylase and phosphoenolpyruvate carboxykinase
- Fructose 1,6-biphosphatase
- Glucose 6-phosphatase
First step of gluconeogenesis (3):
what is it+catayzed by + occurs at
- The first step in gluconeogenesis is the carboxylation of pyruvate to form oxaloacetate at the expense of a molecule of ATP (and a molecule of CO2)
- A reaction catalyzed by pyruvate carboxylase.
- This reaction occurs in the mitochondria.
Gluconeogenesis vs Glycolysis in terms of energy
- gluconeogenesis consumes more energy than glycolysis produces
Pyruvate carboxylase requires —–, a covalently attached prosthetic group that serves as the carrier of activated CO2
- biotin ( transports CO2 from the biotin carboxylase active site to the pyruvate carboxylase active site )
Pyruvate carboxylase
- functions as a tetramer composed of four identical subunits, and each subunit consists of four domains
Second step of gluconeogenesis (3):
Must be (overview)+first Oxaloacetate is+ transported
- Oxaloacetate must be transported to the cytoplasm (originally in mitochondria from pyruvate carboxylase) to complete the synthesis of phosphoenolpyruvate.
- Oxaloacetate is first reduced to malate by malate dehydrogenase in the mitochondria
- Malate is transported across the mitochondrial membrane into the cytoplasm and reoxidized to oxaloacetate by a cytoplasmic malate dehydrogenase
Third step of gluconeogenesis (3)
what happens+enzyme+uses…
- oxaloacetate is simultaneously decarboxylated and phosphorylated by phosphoenolpyruvate carboxykinase (PEPCK) to generate phosphoenolpyruvate.
- The phosphoryl donor is GTP.
- The CO2 that was added to pyruvate by pyruvate carboxylase comes off in this step
This pair of reactions bypasses the irreversible reaction catalyzed by pyruvate kinase in glycolysis:
The sum of the reactions catalyzed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase
Why is a carboxylation and a decarboxylation required to form phosphoenolpyruvate from pyruvate?
- The presence of a phosphoryl group traps the unstable enol isomer of pyruvate as phosphoenolpyruvate. However, the addition of a phosphoryl group to pyruvate is a highly unfavorable reaction: the use of the carboxylation and decarboxylation steps results in a much more favorable way
The formation of oxaloacetate from malate also provides —- for use in subsequent steps in gluconeogenesis.
NADH
Step 4 of glycolysis: The newly formed phosphoenolpyruvate is then metabolized by the enzymes of glycolysis but in the reverse direction. These reactions are near equilibrium under intracellular conditions, so when conditions favor gluconeogenesis, the reverse reactions will take place until the next irreversible step is reached. This step is the…
- hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and Pi with water
The final step in the generation of free glucose takes place primarily in the ….
liver
Step 5 of Glycolysis: Free glucose is not formed in the cytoplasm.
Rather, glucose 6-phosphate is…..
transported into the lumen of the endoplasmic reticulum, where it is hydrolyzed (with water) to glucose by glucose 6-phosphatase, which is bound to the lumen side of the endoplasmic reticulum membrane. Glucose and Pi are then shuttled back to the cytoplasm by a pair of transporters.
The equation for gluconeogenesis is
The extra cost of gluconeogenesis is ——- for each molecule of glucose synthesized from pyruvate. The additional molecules are needed to turn an energetically unfavorable process (the reversal of glycolysis) into a favorable one (gluconeogenesis)
- four high phosphoryl-transfer-potential molecules
The rate of glycolysis is also determined by the concentration of —–, and the rate of gluconeogenesis is controlled by the concentrations of —– and other ——
- glucose
- lactate
- precursors of glucose
AMP stimulates —- but inhibits —–
- phosphofructokinase
- fructose 1,6-bisphosphatase
ATP and citrate inhibit —-, whereas citrate activates —–
- phosphofructokinase
- fructose 1,6-bisphosphatase
In the liver, rates of glycolysis and gluconeogenesis are adjusted to maintain blood-glucose concentration:
fructose 2,6-bisphosphate is a potent activator of phosphofructokinase (PFK), the primary regulatory enzyme in glycolysis. Fructose 2,6-bisphosphate is also an inhibitor of fructose 1,6-bisphosphatase. When blood glucose concentration is low, fructose 2,6-bisphosphate is dephosphorylated to form fructose 6-phosphate, which no longer activates PFK.
How is the amount of fructose 2,6-bisphosphate controlled to rise and fall with blood-glucose concentration?
Two enzymes regulate the concentration of this molecule: one phosphorylates fructose 6- phosphate and the other dephosphorylates fructose 2,6- bisphosphate. Fructose 2,6-bisphosphate is formed from fructose 6-phosphate in a reaction catalyzed by phosphofructokinase 2 (PFK2), a different enzyme from phosphofructokinase. In the reverse direction, fructose 6-phosphate is formed through the hydrolysis of fructose 2,6-bisphosphate by a specific phosphatase, fructose 2,6-bisphosphatase (FBPase2).
What controls whether PFK2 or FBPase2 dominates the bifunctional enzyme’s activities in the liver? The activities of PFK2 and FBPase2 are reciprocally controlled by the ——–
phosphorylation of a single serine residue
This covalent modification activates FBPase2 and inhibits PFK2, lowering the concentration of F-2,6-BP. …….. predominates.
Gluconeogenesis
Phosphorylation of the bifunctional enzyme and, leads to a lower level of —–
phosphofructokinase 2 (PFK2)
A low blood-glucose concentration as signaled by glucagon leads to
the phosphorylation of the bifunctional enzyme and, hence, to a lower level of fructose 2,6-bisphosphate, slowing glycolysis
What impacts fructose 1,6-biphosphatase? (3)
- F-2,6-BP
- AMP
- Citrate
Phosphofructokinase (5)
- F-2,6BP
- AMP
- ATP
- Citrate
- H+
