Glycolysis

Question 1

Main GLUT Transporters

Answer 1

• GLUT 2:
  
  • Found in hepatocytes and pancreatic cells
  • Higher K_m (15 mM)
  • Liver will pick up glucose for storage proportional to its concentration in the blood (first-order kinetics)
  • ß-islet cells of pancreas, along with glucokinase, serve as the glucose sensor for insulin release
• GLUT 4:
  
  • Found in myocytes and adipocytes
  • Insulin stimulates movement of GLUT 4 transporters to membrane by exocytosis
  • Lower K_m (5 mM); at high glucose concentration, transporters permit only a constant rate of glucose influx because they will be saturated (zero-order kinetics)

Question 2

Action and Regulation of Hexokinase and Glucokinase

Answer 2

• phosphorylate glucose to form G6P and prevent it from leaving the cell
• Hexokinase is widely distributed in the tissues and is inhibited by its own product, G6P
  
  • ​Lower K_m
• Glucokinase is found only in liver cells and pancreatic ß- islet cells
  
  • in the liver, glucokinase is induced by insulin
  • _g_lucokinase acts as the glucose sensor with GLUT 2 in pancreatic cells
  • Higher K_m

Question 3

Action and Regulation of PFK-1 and PFK-2

Answer 3

• PFK-1:
  
  • rate-limiting enzyme and main control point in glycolysis
  • phosphorylates F6P to F 1,6-BP using ATP
  • inhibited by ATP and citrate
  • ​​activated by AMP and F 2,6-BP (overrides inactivation by ATP to allow glycolysis to continue to metabolites can be used elsewhere)
• _​_PFK-2:
  
  • converts F6P to F 2,6-BP, which activates PFK-1
  • found mostly in the liver (see above role or F 2,6-BP; this is crucial in the liver to allow metabolites of continued glycolysis to be redirected)
  • activated by insulin
  • inhibited by glucagon

Question 4

Action and Regulation of GAP Dehydrogenase

Answer 4

• catalyzes oxidation and phosphorylation of GAP to 1,3-BPG
• reduces NAD⁺ to NADH

Question 5

Action and Regulation of 3-Phosphoglycerate Kinase

Answer 5

• transfer high-energy phosphate from 1,3-BPG to ADP, forming ATP and 3PG
  
  • (substrate-level phosphorylation)

Question 6

Action and Regulation of Pyruvate Kinase

Answer 6

• last enzyme in aerobic glycolysis
• catalyzes substrate-level phosphorylation of ADP using higher-energy substrate PEP
• activated by F 1,6-BP from PFK-1 reaction (feed-forward activation)

Question 7

Glycolysis Step 1

Answer 7

Question 8

Glycolysis Step 2

Answer 8

Question 9

Glycolysis Step 3

Answer 9

Question 10

Glycolysis Step 4

Answer 10

Question 11

Glycolysis Step 5

Answer 11

Question 12

Glycolysis Step 6

Answer 12

Question 13

Glycolysis Step 7

Answer 13

Question 14

Glycolysis Step 8

Answer 14

Question 15

Glycolysis Step 9

Answer 15

Question 16

Glycolysis Step 10

Answer 16

Question 17

PDH Complex Reaction

Answer 17

• converts pyruvate to acetyl-CoA
• irreversible
• inhibited by acetyl-CoA
• PDH in the liver is activated by insulin, but PDH in the nervous system is resistant to hormones
  
  • (high insulin signals to the liver that the individual is in a well-fed state and should not only burn glucose for energy but shift the fatty acid equilibrium toward production and storage, rather than oxidation)
• Equation:
  
  • pyruvate + NAD⁺ + CoA → acetyl-CoA + NADH + CO₂
• Required Coenzymes:
  
  • TPP, lipoic acid, CoA, FAD, NAD⁺

Question 18

Fermentation

Answer 18

• occurs in the absence of oxygen
  
  • Mammalian Cells: pyruvate → lactate
  • Yeast Cells: pyruvate → ethanol
• Enzyme: lactate dehydrogenase
  
  • oxidizes NADH to NAD⁺, regenerating the coenzyme needed for the GAP dehydrogenase reaction

Question 19

Diagram: Full Process of Glycolysis

Answer 19

Question 20

Important Intermediates of Glycolysis

Answer 20

• DHAP:
  
  • used in hepatic and adipose tissue for triacylglycerol synthesis
  • DHAP is formed from F 1,6-BP and can be isomerized to glycerol 3-phosphate, which can then be converted to glycerol
• 1,3-BPG and PEP:
  
  • high energy intermediates used to generate ATP by substrate-level phosphorylation
  • generate only ATP gained in anaerobic respiration

Question 21

Irreversible Enzymes in Glycolysis

Answer 21

Step 1: Glucokinase/Hexokinase

Step 3: PFK-1

Step 10: Pyruvate Kinase

Question 22

Glycolysis in Erythrocytes and 2,3-BPG

Answer 22

• anaerobic glycolysis is the only pathway for ATP production in RBCs
• RBCs have bisphosphoglycerate mutase, which produces 2,3-BPG from 1,3-BPG
  
  • 2,3-BPG bind allosterically to the ß-chains of HbA and decreases its affinity for oxygen: this allows for greater unloading of oxygen in tissues while still allowing for 100% saturation in the lungs
  • 2,3-BPG does not bind well to fetal hemoglobin (HbF) = HbF has a higher affinity for oxygen, allowing transplacental passage of oxygen from mother to fetus

Question 23

Galactose Metabolism

Answer 23

• lactose is hydrolyzed to galactose and glucose by lactase; galactose reaches the liver via the hepatic portal vein (as is typical of other monosaccharides)
• Steps:
  
  • 1. galactose is phosphorylated by galactokinase to form galactose 1-P
  • 2. galactose 1-P is converted to glucose 1-P by galactose 1-P uridyltransferase and an epimerase

Question 24

Fructose Metabolism

Answer 24

• sucrose is hydrolyzed by sucrase to glucose and fructose
• fructose is absorbed in the hepatic portal vein (with other monosaccharides)
  
  • Steps:
    
    • 1. fructokinase in the liver phosphorylates fructose to fructose 1-P
    • 2. fructose 1-P is cleaved into glyceraldehyde and DHAP by aldolase B