Glycolysis + Fates of pyruvate/cori cycle

Glycolysis preparatory phase

traps glucose in the cell and modifies it so that it can be cleaved into a pair of phosphorylated 3-carbon compounds. Activate by phosphorylation

Glycolysis payoff stage

oxidizes the 3-carbon compounds to pyruvate while generating 2 molecules of ATP. Payoff phase. Collect energy from high energy metabolites

Glucose

Most stable hexose alpha - down beta - up

Glucose to G6P

1. hexokinase

2. Favorable (-16.7 kJ/mol) (irreversible)

3. uses ATP + Mg2+

G6P to F6P

1. phosphoglucose isomerase

2. unfavorable (1.7 kJ/mol)

3. glutamate helps with breaking the ring by acting as a base

F6P to F1,6BP

1. phosphofructokinase-1

2. favorable (-14.2 kJ/mol)

3. first committed step

4. ATP + Mg2+

F1,6BP to DHAP + GAP

1. aldolase

2. unfavorable (23.8 kJ/mol)

3. lysine used (schiff base). nucleophile = nitrogen on lys; electrophile = second carbon in F1,6BP

DHAP to GAP

1. TIM

2. unfavorable, but GAP concentration is kept low, allowing reaction to go forward (Le Chatelier)

3. creates enediol intermediate which is unstable

GAP to 1,3-BPG

1. GAPDH/G3P DH

2. unfavorable (6.3 kJ/mol)

3. NAD+ (only oxidation step) + H+

4. uses cysteine (form a thioester and decrease the free energy) and histidine (aid oxidation)

1,3-BPG to 3-PG

1. phosphoglycerate kinase

2. favorable (-18.6 kJ/mol)

3. reversible due to coupling of GADPH

4. 1st ATP produced

3-PG to 2-PG

1. phosphoglycerate mutase

2. unfavorable (4.6 kJ/mol)

3. uses 2 histidines

2-PG to PEP (phosphoenolpyruvate)

1. enolase

2. unfavorable (1.7 kJ/mol)

3. reversible, because product concentration is kept low enough to go forward

4. uses lys and hist

5. produces 2 H2O

PEP to pyruvate

1. pyruvate kinase

2. favorable (-31.4 kJ/mol)

3. ATP produced

4. Tautomerizes into ketone

Thioester intermediate is ________ in energy

high

Net reaction for glycolysis

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

What type of bond is broken in aldolase?

C-C

What product leaves first in aldolase rxn?

G3P

What is the importance of the thioester intermediate?

Higher energy, easier to overcome

Which steps are coupled?

GAP to 1,6BPG

Pyruvate + Pyruvate decarboxylase

Acetylaldehyde + CO2

Acetaldehyde to ethanol

Alcohol dehydrogenase (NADH used to produce NAD+)

Pyruvate to Lactate enzyme

Lactate dehydrogenase (uses NADH + H+)

Purpose of lactic acid fermentation

Lactate does not cause negative feedback of glycolysis and regenerates NAD+ to be used in glycolysis