Glycolysis

Overview of Glycolysis

  • Glycolysis consists of 10 enzymatic reactions.

  • Key Outputs: ATP and NADH.

  • Importance of Energy Deposits: An initial energy deposit is needed to initiate glycolysis, yielding energy later in the pathway.

Reaction Steps in Glycolysis

Reaction 1: Formation of Glucose 6 Phosphate

  • Enzyme: Hexokinase (found in red blood cells and tissues) and Glucokinase (found in the liver and pancreas).

  • Process: Phosphorylation of glucose by ATP. This phosphoryl group is transferred to glucose, forming glucose 6 phosphate.

  • Regulation: This is a regulated and slow step due to its essential role in glycolysis.

  • Mechanism: Induced fit mechanism of enzyme formation around glucose.

  • Cofactor: Magnesium stabilizes the phosphate during this reaction.

Reaction 2: Isomerization of Glucose 6 Phosphate to Fructose 6 Phosphate

  • Purpose: Converts glucose 6 phosphate to fructose 6 phosphate; prepares substrate for further phosphorylation.

  • Carbon Atoms: Positions carbon atoms outside the ring to facilitate the next step in the pathway.

  • Carbon Positions:

    • Glucose: C1 (attached phosphate), C2, C3, C4, C5, C6

    • Fructose: C1, C2 (attached hydroxyl group), C3, C4

Reaction 3: Phosphorylation of Fructose 6 Phosphate to Fructose 1,6 Bisphosphate

  • Type: Energy deposit step (uses ATP, consuming 2 ATP by this point in glycolysis).

  • Regulation: This is another regulated and rate-limiting step.

  • Mechanism: An ATP molecule donates a phosphate to carbon 1, resulting in fructose 1,6 bisphosphate (two phosphates on C1 and C6).

  • Notation: "Bis" or "di" prefix indicates two phosphate groups.

Reaction 4: Cleavage of Fructose 1,6 Bisphosphate

  • Enzyme: Aldolase.

  • Process: Reverse aldol condensation, splitting fructose into two three-carbon molecules: glyceraldehyde 3 phosphate (G3P) and dihydroxyacetone phosphate (DHAP).

  • Carbon Breakdown:

    • G3P: C1, C2, C3

    • DHAP: C4, C5, C6

Reaction 5: Conversion of DHAP to G3P

  • Clarification: Each G3P molecule is produced (two G3P from the original fructose).

  • End of Energy Investment Phase: This marks the conclusion of energy deposit reactions.

Reaction 6: Formation of 1,3 Bisphosphoglycerate from G3P

  • Enzyme: Dehydrogenase (signaling a redox reaction).

  • Process: G3P is oxidized, resulting in 1,3 bisphosphoglycerate (BPG) via addition of inorganic phosphate; does not utilize ATP.

  • Products: 2 NADH per glucose (2 G3P produce 2 NADH).

Reaction 7: Conversion of 1,3 Bisphosphoglycerate to 3 Phosphoglycerate

  • Enzyme: A kinase.

  • Process: ATP is generated by transferring a phosphate from BPG to ADP, forming ATP and 3-phosphoglycerate.

  • Products: 2 ATP generated.

Reaction 8: Isomerization from 3 Phosphoglycerate to 2 Phosphoglycerate

  • Mechanism: Shift of the phosphate group from C3 to C2 to make the molecule more stable, facilitating easier ATP release.

Reaction 9: Dehydration to Form Phosphoenolpyruvate (PEP)

  • Process: Removal of a water molecule from 2-phosphoglycerate, leading to the formation of PEP.

Reaction 10: Substrate-Level Phosphorylation to Form Pyruvate

  • Enzyme: A kinase.

  • Process: PEP donates phosphate to ADP forming ATP and producing two pyruvate molecules.

  • Regulation: Another regulated step.

  • Outcome: 2 ATP generated in this step.

Summary of Glycolysis

  • Net Yield:

    • 2 ATP (net gain after considering deposits).

    • 2 NADH per glucose.

    • 2 Pyruvate molecules as final products.

  • Implications: Reaction processes and substrates are critical for cellular metabolism and energy production, linking with further metabolic pathways like the citric acid cycle.