Glycolysis

1. Glycolysis

2. 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.

3. 3 regulated steps 10 steps No O2 Glucose Glycolysis Pyruvate Lactate Eric Niederhoffer SIU-SOM Energy (ATP) and metabolites Net Reaction: Glucose + 2NAD+ + 2 Pi + 2 ADP = 2 pyruvate + 2 ATP + 2 NADH + 2 H2O

7. Outputs: 2 pyruvate 2 NADH 2 ADP 2 ATP (net gain) Glycolysis summary • Inputs: • Glucose • 2 NAD+ • 2 ATP • 4 ADP + 4P

9. Regulation of Glycolysis • Steps 1, 3 and 10 are regulatory • 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.

10. 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.

11. Step 10 • Pyruvate Kinase

12. Summary of 10 steps

13. Regulation