Glucose metabolism

Question 1

Glucose transporters

Answer 1

Transported by active transport in the gut and facilitated diffusion elsewhere.

The GLUT transporter proteins help with transport.

Question 2

Glucose transporters

GLUT-2

Answer 2

Located in pancreas and liver tissues.
Has a high Km (low affinity).
Only transporter that is bidirectional (glucose going both into and out of cells).

Question 3

Glucose transporters

GLUT-4

Answer 3

Found in adipose and muscle tissues.
Has a low Km (high affinity).
The only transporter that requires stimulation by insulin.

Question 4

Key enzymes of gluconeogenesis

Glucose 6-phosphatase

Answer 4

Converts glucose 6-phosphate to glucose through a hydrolysis reaction. Bypasses the glucokinase/hexokinase step from glycolysis.
Found only in the liver.

Question 5

Key enzymes of gluconeogenesis

Fructose-1,6-bisphosphatase

Answer 5

Converts fructose 1,6-bisphosphate to fructose 6-phosphate, bypassing PFK-1.
Activated by ATP, glucagon and inhibited by AMP, insulin.
This is the rate-limiting step of gluconeogenesis.

Question 6

Key enzymes of gluconeogenesis

Pyruvate carboxylase

Answer 6

Converts pyruvate to oxaloacetate which leaves the mitochondria. Activated by acetyl-CoA.
Pyruvate carboxylase and fructose-1,6-bisphosphatase are the main regulatory enzymes.

Question 7

Key enzymes of gluconeogenesis

Phosphoenolpyruvate carboxykinase (PEPCK)

Answer 7

Converts oxaloacetate to PEP. Works with pyruvate carboxylase to bypass pyruvate kinase from glycolysis.

Question 8

Key enzymes of glycolysis

Glucokinase

Answer 8

Catalyzes conversion of glucose to G6P in the pancreas and liver. The initial step of glycolysis.
Prevents glucose from escaping through its conversion.

Question 9

Key enzymes of glycolysis

Hexokinase

Answer 9

Catalyzes conversion of glucose to G6P in the peripheral tissues.
Inhibited by feedback from G6P (its product).

Question 10

Key enzymes of glycolysis

Phosphofructokinase-1

Answer 10

Catalyzes conversion of F6P → F-1,6BP with ATP → ADP.
Inhibited by signals of high energy: ATP and citrate. Activated by low energy signal AMP or F-2,6BP.
The rate-limiting step of glycolysis.

Question 11

Key enzymes of glycolysis

Phosphofructokinase-2

Answer 11

Catalyzes production of F-2,6BP which allows continued activation of PFK-1 in the liver even with abundance of ATP.
Activated by insulin and inhibited by glucagon.

Question 12

Key enzymes of glycolysis

Pyruvate kinase

Answer 12

Performs substrate-level phosphorylation, specifically conversion of phosphoenolpyruvate (PEP) to pyruvate with ADP to ATP.
This enzyme is a transferase that transfers an inorganic phosphate onto ADP.
Activated by F-1,6BP whose production is catalyzed by PFK-1. Inhibited by its product ATP.

Question 13

Key enzymes of glycolysis

Glyceraldehyde-3-phosphate (G3P) dehydrogenase

Answer 13

Produces NADH which is the substrate for the electron transport chain under aerobic conditions.

Question 14

The production of glucose from carbon substrates (like pyruvate).
Think of this as the inverse of glycolysis.

Answer 14

gluconeogenesis

Question 15

Principles of gluconeogenesis

Bypassing glycolysis

Answer 15

The reversible reactions of glycolysis use the same enzymes in gluconeogenesis while the irreversible reactions of glycolysis are bypassed by different enzymes.

• Pyruvate kinase is bypassed by PEPCK and pyruvate carboxylase.
• PFK-1 is bypassed by fructose 1,6-bisphosphatase.
• Hexokinase is bypassed by glucose-6-phosphatase.

Question 16

Principles of gluconeogenesis

Hormone regulation

Answer 16

Activated by glucagon and cortisol.
Inhibited by insulin.

Question 17

Principles of gluconeogenesis

Rate-limiting step

Answer 17

Catalyzed by fructose 1,6-bisphosphatase.

Question 18

Principles of gluconeogenesis

Location

Answer 18

Within the cell, occurs in the cytoplasm and mitochondria.
In terms of organ location, primarily in the liver with some occurring in kidneys.

Question 19

Steps 1-2 of glycolysis

Answer 19

Question 20

Steps 3-4 of glycolysis

Answer 20

Question 21

Steps 5-6 of glycolysis

Answer 21

Question 22

Steps 7-8 of glycolysis

Answer 22

Question 23

Steps 9-10 of glycolysis

Answer 23

Question 24

Steps 1-2 of glycolysis

Question 25

Steps 3-4 of glycolysis

Question 26

Steps 5-6 of glycolysis

Question 27

Steps 7-8 of glycolysis

Question 28

Steps 9-10 of glycolysis

Answer 28

Question 29

Principles of glycolysis

Overall reaction

Answer 29

Glucose + 2NAD+ + 2ADP + 2P → 2 Pyruvate + 2 ATP (net) + 2 NADH + 2 H+

Question 30

Principles of glycolysis

Enzymes of irreversible steps

Answer 30

The kinases glucokinase, hexokinase, PFK-1, and pyruvate kinase catalyze irreversible reactions.
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Question 31

Principles of glycolysis

Key step

Answer 31

Fructose-6-phosphate → fructose-1,6-bisphosphate, catalyzed by PFK-1.
This is the rate-limiting step as well as the committed step (can no longer be redirected to glycogenesis pathway).

Question 32

Principles of glycolysis

Link to other pathways

Answer 32

Glucose-6-phosphate from the glycolysis pathway is the primary substrate for glycogenesis.
DHAP is used for fatty acid synthesis.

Question 33

Principles of glycolysis

Anaerobic conditions

Answer 33

In absence of oxygen, pyruvate must be converted to lactic acid to regenerate NAD+.

Question 34

Principles of glycolysis

Overall pathway

Answer 34

Glucose → G6P → F6P → F1,6BP → GADP + DHAP → 1,3BPG → 3PG → 2PG → PEP → Pyruvate