Steps of Glycolysis — Revision Notes

⚡ 30-Second Revision

Overall: — Glucose (6C) $\rightarrow$ 2 Pyruvate (3C)
Location: — Cytoplasm
Net Yield: — 2 ATP, 2 NADH
Key Enzymes (Irreversible Steps):

- Step 1: Hexokinase/Glucokinase - Step 3: Phosphofructokinase-1 (PFK-1) - Rate-limiting - Step 10: Pyruvate Kinase

ATP Consumed: — 2 ATP (Steps 1, 3)
ATP Produced: — 4 ATP (Steps 7, 10 - each occurs twice)
NADH Produced: — 2 NADH (Step 6 - occurs twice)
Splitting Step: — Step 4 (Fructose-1,6-bisphosphate $\rightarrow$ DHAP + GAP by Aldolase)
Inorganic Phosphate ($P_i$) use: — Step 6 (Glyceraldehyde-3-phosphate Dehydrogenase)

2-Minute Revision

Glycolysis is the initial breakdown of glucose into two pyruvate molecules, occurring in the cytoplasm. It's an anaerobic process, meaning it doesn't require oxygen. The pathway is divided into two main phases.

The 'energy investment phase' (Steps 1-5) consumes 2 ATP molecules to phosphorylate glucose and its derivatives, making them reactive and trapping them within the cell. Key enzymes here include Hexokinase (Step 1) and the crucial regulatory enzyme Phosphofructokinase-1 (PFK-1, Step 3).

This phase also involves the splitting of a 6-carbon sugar (Fructose-1,6-bisphosphate) into two 3-carbon molecules (DHAP and GAP). The 'energy payoff phase' (Steps 6-10) then generates energy. Here, 2 NADH molecules are produced in Step 6, and 4 ATP molecules are produced via substrate-level phosphorylation in Steps 7 and 10.

The net energy yield is 2 ATP and 2 NADH per glucose molecule. The three irreversible steps (Steps 1, 3, 10) are critical for regulation, ensuring the pathway responds to cellular energy demands. Pyruvate's fate depends on oxygen availability, either entering the mitochondria for aerobic respiration or undergoing fermentation anaerobically.

5-Minute Revision

Glycolysis, the 'sugar splitting' pathway, is a universal cytoplasmic process that converts one molecule of 6-carbon glucose into two molecules of 3-carbon pyruvate. It's vital for immediate energy supply, especially in anaerobic conditions. The pathway proceeds in 10 steps, categorized into two phases.

Phase 1: Energy Investment (Steps 1-5)

1
Glucose $\rightarrow$ Glucose-6-phosphate: — Catalyzed by Hexokinase (or Glucokinase). Consumes 1 ATP. Irreversible. Traps glucose.
2
Glucose-6-phosphate $\rightarrow$ Fructose-6-phosphate: — Phosphoglucose Isomerase. Reversible isomerization.
3
Fructose-6-phosphate $\rightarrow$ Fructose-1,6-bisphosphate: — Phosphofructokinase-1 (PFK-1). Consumes 1 ATP. Irreversible. Rate-limiting and major regulatory step.
4
Fructose-1,6-bisphosphate $\rightarrow$ Dihydroxyacetone phosphate (DHAP) + Glyceraldehyde-3-phosphate (GAP): — Aldolase. The 'splitting' step.
5
DHAP $\rightarrow$ GAP: — Triose Phosphate Isomerase. Reversible. Ensures both 3-carbon units proceed.

*Total ATP invested: 2 ATP*

Phase 2: Energy Payoff (Steps 6-10) (Each step occurs twice per glucose)

1
GAP $\rightarrow$ 1,3-Bisphosphoglycerate: — Glyceraldehyde-3-phosphate Dehydrogenase. Produces 1 NADH (from NAD$^+$) and incorporates 1 inorganic phosphate ($P_i$).
2
1,3-Bisphosphoglycerate $\rightarrow$ 3-Phosphoglycerate: — Phosphoglycerate Kinase. Produces 1 ATP (substrate-level phosphorylation).
3
3-Phosphoglycerate $\rightarrow$ 2-Phosphoglycerate: — Phosphoglycerate Mutase. Reversible phosphate shift.
4
2-Phosphoglycerate $\rightarrow$ Phosphoenolpyruvate (PEP): — Enolase. Dehydration, forms high-energy phosphate bond.
5
PEP $\rightarrow$ Pyruvate: — Pyruvate Kinase. Produces 1 ATP (substrate-level phosphorylation). Irreversible. Major regulatory step.

Net Yield: 2 ATP (4 produced - 2 consumed) and 2 NADH. The NADH can yield more ATP in aerobic respiration (via ETC) or be reoxidized to NAD$^+$ in fermentation (anaerobic) to keep glycolysis running. Pyruvate's fate is either aerobic oxidation to acetyl-CoA or anaerobic fermentation to lactate/ethanol.

Prelims Revision Notes

Glycolysis is a 10-step metabolic pathway occurring in the cytoplasm, breaking down glucose into two pyruvate molecules. It's an anaerobic process, yielding a net of 2 ATP and 2 NADH per glucose.

Energy Investment Phase (Steps 1-5):

Step 1: — Glucose $\xrightarrow{\text{Hexokinase/Glucokinase}}$ Glucose-6-phosphate. Uses 1 ATP. Irreversible.
Step 2: — Glucose-6-phosphate $\xrightarrow{\text{Phosphoglucose Isomerase}}$ Fructose-6-phosphate. Reversible.
Step 3: — Fructose-6-phosphate $\xrightarrow{\text{Phosphofructokinase-1 (PFK-1)}}$ Fructose-1,6-bisphosphate. Uses 1 ATP. Irreversible. Rate-limiting step.
Step 4: — Fructose-1,6-bisphosphate $\xrightarrow{\text{Aldolase}}$ Dihydroxyacetone phosphate (DHAP) + Glyceraldehyde-3-phosphate (GAP). Reversible.
Step 5: — DHAP $\xrightarrow{\text{Triose Phosphate Isomerase}}$ GAP. Reversible. Ensures both 3-carbon units proceed.

Energy Payoff Phase (Steps 6-10) - occurs twice per glucose:

Step 6: — GAP $\xrightarrow{\text{Glyceraldehyde-3-phosphate Dehydrogenase}}$ 1,3-Bisphosphoglycerate. Produces 1 NADH + H$^+$. Incorporates inorganic phosphate ($P_i$).
Step 7: — 1,3-Bisphosphoglycerate $\xrightarrow{\text{Phosphoglycerate Kinase}}$ 3-Phosphoglycerate. Produces 1 ATP (substrate-level phosphorylation).
Step 8: — 3-Phosphoglycerate $\xrightarrow{\text{Phosphoglycerate Mutase}}$ 2-Phosphoglycerate. Reversible.
Step 9: — 2-Phosphoglycerate $\xrightarrow{\text{Enolase}}$ Phosphoenolpyruvate (PEP). Produces H$_2$O.
Step 10: — PEP $\xrightarrow{\text{Pyruvate Kinase}}$ Pyruvate. Produces 1 ATP (substrate-level phosphorylation). Irreversible.

Net Energy Yield: 2 ATP (4 produced - 2 consumed), 2 NADH. Fate of Pyruvate: Aerobic $\rightarrow$ Acetyl-CoA (Krebs cycle); Anaerobic $\rightarrow$ Lactate or Ethanol (fermentation to regenerate NAD$^+$).

Vyyuha Quick Recall

Here's a mnemonic for the 10 enzymes of glycolysis: He Plays Pop And Then Gets Paid Pretty Enormous Paychecks.

1
Hexokinase
2
Phosphoglucose Isomerase
3
Phosphofructokinase-1
4
Aldolase
5
Triose Phosphate Isomerase
6
Glyceraldehyde-3-phosphate Dehydrogenase
7
Phosphoglycerate Kinase
8
Phosphoglycerate Mutase
9
Enolase
10
Pyruvate Kinase