Glycolysis 1. The Glycolytic Pathway 2. The Reactions of Glycolysis By: Mohammed Imran Anees Y.B.C.C.P Aurangabad

Glycolysis Glucose is converted to pyruvate while generating two ATPs. 2 molecules of NAD+ are converted to 2 molecules of NADH. The oxidizing power of NAD+ must be recycled. Figure 16-1 Glycolysis overview

Pathway Overview There are 10 enzyme-catalyzed reactions considered to occur in two stages Stage I (reactions 1-5): Preparatory stage where glucose is phosphorylated and cleaved to yield 2 molecules of glyceraldehyde-3-phosphate (GAP). Stage I uses 2 ATPs. Stage II (reactions 6-10) Payoff stage where 2 GAPs converted to pyruvate and generation of 4 ATPs.

The Reactions of Glycolysis Stage I (Preparatory Stage) 1. Hexokinase (first ATP utilization) 2. Phosphoglucose Isomerase (PGI) 3. Phosphofructokinase -1 (PFK-1) (second ATP utilization) 4. Aldolase 5. Triose Phosphate Isomerase (TIM)

THE PREPARATORY PHASE Step 1 – Hexokinase Hoexokinase (first ATP utilization)

Step 2 – Phosphoglucose Isomerase (PGI) [Phosphohexose isomerase] catalyzes the conversion of G6P to F6P, the isomerization of an aldose to a ketose. Phosphoglucose Isomerase (PGI)

The isomerization of an aldose to a ketose

(C) Step 3 - Phosphofructokinase 1: Second ATP utilization Phosphofructokinase: Second ATP Utilization

D. Step 4 - Aldolase Aldolase catalyzes cleavage of fructose-1,6-bisphosphate (FBP) in reaction 4 of glycolysis. This forms two trioses Glyceraldehyde-3-phosphate (GAP) Dihydroxyacetone phosphate (DHAP).

Step 4 - Aldolase. Aldol cleavage of FBP to form two Trioses (GAP and DHAP) Note that the atom numbering system changes. Atoms 1, 2, and 3 of glucose become atoms 3,2, and 1 of DHAP. Atoms 4, 5, and 6 become atoms 1, 2, and 3 of GAP. Cleavage of FBP to form two trioses.

(E) Step 5 - Triose Phosphate Isomerase (TIM) Only GAP continues along the glycolytic pathway. TIM – the final reaction of Stage I.

Stage II - payoff phase 6. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) first "High-energy" intermediate formation. 7. Phosphoglycerate Kinase (PGK): First ATP Generation. 8. Phosphoglycerate Mutase (PGM). 9. Enolase: second "High-energy" intermediate formation. 10. Pyruvate Kinase (PK): Second ATP generation.

(F) Step 6 - Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH): First “High-Energy” Intermediate Formation.

(G). Step 7 - Phosphoglycerate Kinase (PGK): First ATP Generation.

Mechanism of the PGK reaction. Figure 16-16 The mechanism of the PGK reaction. The Mg2+ positions are shown as examples; their actual binding sites are unknown.

(H). Step 8 - Phosphoglycerate Mutase (PGM).

(I) Step 9 - Enolase: Second “High-Energy” Intermediate Formation (I) Step 9 - Enolase: Second “High-Energy” Intermediate Formation. (Dehydration reaction) Enolase

(J) Step 10 - Pyruvate Kinase (PK) : Second ATP Generation.

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