Glycolysis

Question 1

What are the three stages of Glycolysis

Answer 1

1) Activation (first three reactions)
2) Split/ Isomerization ( 2 reactions)
3) Extraction (last five reactions)

Question 2

First Step of glycolysis

Answer 2

Goal: phosphorylate glucose (glucose 6-phosphate) using hexokinase
Mammal glucose transporters do not recognize glucose 6-phosphate and the negative charge prevents membrane diffusion
(Trap glucose in the cell)

Question 3

Why is induce fit important for hexokinase

Answer 3

In the cell water concentration is extremely high and if water is in the active site, it will hydrolysis ATP to ADP.
Induce fit allows glucose access to the active site, but then excludes any water binding

Question 4

Second Step

Answer 4

Phosphoglucose Isomerase catalyzes the reaction to convert G6P into Fructose-6-phosphate (aldose form to ketone)

Question 5

Third Step

Answer 5

Committed Step (highly regulated)
Phosphofructokinase (PFK) catalyzes phosphorylation of F6P to Fructose-1,6-biphosphate (FBP)
Uses another ATP

Question 6

Fourth Step

Answer 6

Delta G is very positive (+22.8)
Aldo last splits the 6-C sugar into 2x 3-C molecules and both are ephosphorylated once
FBP to DHAP and Glyceraldehyde-3-phosphate (GAP)

Question 7

How does the cell use DHAP

Answer 7

Used to lipid synthesis, not able to continue through glycolysis like GAP

Question 8

Fifth Step

Answer 8

Triose phosphate isomerase (TPI or TIM) interconverts DHAP and GAP. This allows DHAP to continue through glycolysis.
DHAP is preferred thermodynamically, therefore all runs in stage 3 are fast and therefore [GAP] is low allows the reaction to push to the GAP product.

Question 9

What happens if the concentration of DHAP gets too high

Answer 9

Can become methyglyoxal which is extremely cytotoxic and reactions with lysines and arginines. Seen with high glucose in diabetes and linked to many diseases.

Question 10

how does the cell fix high concentrations of DHAP

Answer 10

Methylglyoxal Synthase (MGS) synthesizes toxic methylgloxal from DHAP

Question 11

Step 6

Answer 11

GAP dehydrogenase converts GAP to 1,3-BPG using NAD+ and Phosphate (adds Phosphate group to increase energy w/out using ATP)
1) oxidizes an aldehyde to a carboxylic acid (-50kJ/mol)
2) phosphorylation the carboxylic acid (+56kJ/mol) EXTREMELY UNFAVORABLE

Question 12

Step 7

Answer 12

Named for the reverse reaction
Generates 2 ATP/glucose
Phosphoglycerate kinase removes phosphate group from 1,3-biphosphoglyccerate back to 3-Phosphoglycerate

Question 13

Step 8

Answer 13

Phosphoglycerate mutase (moves a functional group) goes from 3-Phosphoglycerate to 2-Phosphoglycerate

Question 14

Step 9

Answer 14

Enolase removes a water (dehydration)
2-Phosphoglycerate (2PG) to Phosphoenolpyruvate (PEP)

Question 15

Step 10

Answer 15

Generates another 1 ATP/glucose with substrate-level phosphorylation

Question 16

Net equation for Glycolysis

Answer 16

Glucose+ 2Pi + 2ADP + 2 NAD+ —> 2 pyruvate + 2 ATP + 2NADH + 2 H+ + 2 H2O

Question 17

What happens to pyruvate after glycolysis

Answer 17

Converted to lactate (1 NAD+), Ethanol (2 NAD+), or Formate (1 acetyl-CoA, 0 NAD+)
In other words, fermentation or respiration