Lecture 21/Textbook Ch. 17: Gluconeogenesis

Question 1

Gluconeogenesis

Answer 1

the synthesis of glucose from noncarbohydrate precursors

Question 2

The major site of gluconeogenesis is the —–, with a small amount also taking place in the —–

Answer 2

• liver
• kidney

Question 3

The gluconeogenic pathway converts —— into glucose.

Answer 3

pyruvate

Question 4

Noncarbohydrate precursors of glucose are first converted into —– or enter the pathway at later intermediates

Answer 4

• pyruvate

Question 5

Lactate is formed by active skeletal muscle through lactic acid fermentation when the rate of glycolysis exceeds the rate at which ——-

Answer 5

muscle can process pyruvate aerobically

Question 6

The enzymes for gluconeogenesis are located in the —-, except for pyruvate carboxylase (in the —–) and glucose 6-phosphatase (membrane bound in the ——)

Answer 6

• cytoplasm
• mitochondria
• endoplasmic reticulum

Question 7

Glucogenesis is the same reactions in reverse compared to glycolysis except the 3 irreversible reactions (3):

Answer 7

1. Pyruvate carboxylase and phosphoenolpyruvate carboxykinase
2. Fructose 1,6-biphosphatase
3. Glucose 6-phosphatase

Question 8

First step of gluconeogenesis (3):

what is it+catayzed by + occurs at

Answer 8

• 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.

Question 9

Gluconeogenesis vs Glycolysis in terms of energy

Answer 9

• gluconeogenesis consumes more energy than glycolysis produces

Question 10

Pyruvate carboxylase requires —–, a covalently attached prosthetic group that serves as the carrier of activated CO2

Answer 10

• biotin ( transports CO2 from the biotin carboxylase active site to the pyruvate carboxylase active site )

Question 11

Pyruvate carboxylase

Answer 11

• functions as a tetramer composed of four identical subunits, and each subunit consists of four domains

Question 12

Second step of gluconeogenesis (3):

Must be (overview)+first Oxaloacetate is+ transported

Answer 12

• 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

Question 13

Third step of gluconeogenesis (3)

what happens+enzyme+uses…

Answer 13

• 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

Question 14

This pair of reactions bypasses the irreversible reaction catalyzed by pyruvate kinase in glycolysis:

Answer 14

The sum of the reactions catalyzed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase

Question 15

Why is a carboxylation and a decarboxylation required to form phosphoenolpyruvate from pyruvate?

Answer 15

• 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

Question 16

The formation of oxaloacetate from malate also provides —- for use in subsequent steps in gluconeogenesis.

Answer 16

NADH

Question 17

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…

Answer 17

• hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and Pi with water

Question 18

The final step in the generation of free glucose takes place primarily in the ….

Answer 18

liver

Question 19

Step 5 of Glycolysis: Free glucose is not formed in the cytoplasm.
Rather, glucose 6-phosphate is…..

Answer 19

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.

Question 20

The equation for gluconeogenesis is

Answer 20

Question 21

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)

Answer 21

• four high phosphoryl-transfer-potential molecules

Question 22

The rate of glycolysis is also determined by the concentration of —–, and the rate of gluconeogenesis is controlled by the concentrations of —– and other ——

Answer 22

• glucose
• lactate
• precursors of glucose

Question 23

AMP stimulates —- but inhibits —–

Answer 23

• phosphofructokinase
• fructose 1,6-bisphosphatase

Question 24

ATP and citrate inhibit —-, whereas citrate activates —–

Answer 24

• phosphofructokinase
• fructose 1,6-bisphosphatase

Question 25

In the liver, rates of glycolysis and gluconeogenesis are adjusted to maintain blood-glucose concentration:

Answer 25

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.

Question 26

How is the amount of fructose 2,6-bisphosphate controlled to rise and fall with blood-glucose concentration?

Answer 26

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).

Question 27

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 ——–

Answer 27

phosphorylation of a single serine residue

Question 28

This covalent modification activates FBPase2 and inhibits PFK2, lowering the concentration of F-2,6-BP. …….. predominates.

Answer 28

Gluconeogenesis

Question 29

Phosphorylation of the bifunctional enzyme and, leads to a lower level of —–

Answer 29

phosphofructokinase 2 (PFK2)

Question 30

A low blood-glucose concentration as signaled by glucagon leads to

Answer 30

the phosphorylation of the bifunctional enzyme and, hence, to a lower level of fructose 2,6-bisphosphate, slowing glycolysis

Question 31

What impacts fructose 1,6-biphosphatase? (3)

Answer 31

• F-2,6-BP
• AMP
• Citrate

Question 32

Phosphofructokinase (5)

Answer 32

• F-2,6BP
• AMP
• ATP
• Citrate
• H+