Glycolysis
Glycolysis Overview
• The Glycolytic pathway describes the oxidation of glucose to
pyruvate with the generation of ATP and NADH
• Glycolysis is a universal pathway; present in all organisms:
from yeast to mammals.
•
•
In eukaryotes, glycolysis takes place in the cytosol
Glycolysis is anaerobic; it does not require oxygen.
• In the presence of O2, pyruvate is further oxidized to CO2.
• In the absence of O2, pyruvate can be fermented to lactate
or ethanol.
Glycolysis
Glucose
10 steps
3 regulated steps
Pyruvate No O2
Lactate
Energy (ATP) and metabolites
Net Reaction:
Glucose + 2NAD+ + 2 Pi + 2 ADP = 2 pyruvate + 2 ATP + 2 NADH + 2 H2O
Eric Niederhoffer
SIU-SOM
Glycolysis summary
•Inputs:
•Glucose
•2 NAD+
•2 ATP
•4 ADP + 4P
•Outputs:
•2 pyruvate
•2 NADH
•2 ADP
•2 ATP (net gain)
Regulation of Glycolysis
•
Steps 1, 3 and 10 are regulatory
1.
First regulatory enzyme – Hexokinase (Step 1)
•
Hexokinase catalyses phosphorylation of Glucose > G-6-P
•
First reversible step of glycolysis
•
•
Glucose >>>>>>> G-6-P (lots) (rate of glycolysis low)
so Hexokinase inhibited (Feed back inhibition)
•
Glucose enters cell but since the hexokinase inactive it can
readily diffuse back to the blood through the glucose
transporter in the plasma membrane.
This step uses ATP so prevent wastage.
•
Step 2 Phosphofructokinase
•
Is the rate limiting enzyme
•
•
Is inhibited by [H+]
Production of lactate leads to an increase in [H+] so
Phosphofructokinase is inhibited. During vigorous exercise all
the lactate can not be removed by the blood leading to a
increase in [H+] causing muscle pain.
•
•
Is inhibited by ATP but stimulated by AMP and Pi
This shows that this enzyme is stimulated when the cell needs
energy.
•
•
Is inhibited by citrate
Is an early intermediate in the TCA cycle. When the TCA
cycle rises citrate is transported out of the mitochondria into
the cytosol and inhibits Phosphofructokinase and so slows
glycolysis.
Step 10
• Pyruvate Kinase
Summary of 10 steps
Step
Importance
Enzyme
Type
1
Traps glucose inside cell
ATP investment
Regulated 1
Hexokinase
Phosphoryl transfer
2
Rearrangement
Phosphoglucose
isomerase
Isomerization
3
Rate limiting step ie committed
step
ATP investment (second)
Major regulation 2
Phosphofructokinase
Phosphoryl transfer
4
Get two, 3 carbon compounds
Aldolase
Aldol cleavage
5
Freely - interconversion
Triose phosphate
isomerase
Isomerization
6
NADH formed i.e. first energy
trapping reaction.
Glyceraldehyde 3phosphate
dehydrogenase
Phosphorylation
coupled to oxidation
7
ATP generation (2)
Substrate level Phosphorylation
Phosphoglycerate
kinase
Phosphoryl transfer
8
Phosphoryl shift
Phospoglyceromutas
e
Phosphoryl shift
9
Energy trapping reaction – in the
form of PEP. (used to generate ATP
in the next rxn)
Enolase
Dehydration
10
ATP generation (2)
Regulated 3
Pyruvate kinase
Phosphoryl transfer
Regulation
Step
Enzyme
Inhibitors
Stimulators
1
Hexokinase
Epinephrine + Glucagon (low
blood glucose)
Insulin
3
Phosphofructokinase
ATP
[H+]
citrate
AMP
F-2,6-BP(learn in detail)
10
Pyruvate kinase
ATP
Glucagon
F1,6-BP (remember is product of
Phosphofructokinase)