Biochemistry · MU Pleven

13. Glucose Metabolism. Glycolysis under Anaerobic Conditions: Main Stages and Reactions. Substrate-level phosphorylation.

Walks through anaerobic glycolysis from glucose to pyruvate and lactate, separating the energy investment phase (two ATP spent, including the rate-limiting PFK-1 step) from the energy generation phase. It explains the single oxidation step, the two substrate-level phosphorylation reactions, and how NAD⁺ is regenerated by lactate dehydrogenase. The note closes with the net yield of two ATP per glucose, the Cori cycle, and clinical examples such as red blood cells, exercising muscle and tumour cells.

Inside: 4 sections · 5 labelled pictures · 10 flashcards · 4 min

Topic 13 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 4 sections, about 592 words (4 min of reading), with 10 flashcards.

In this note

  1. Glucose Metabolism. Glycolysis under Anaerobic Conditions
  2. Glucose Metabolism: Glycolysis under Anaerobic Conditions
  3. Substrate-Level Phosphorylation
  4. Clinical and Physiological Importance

Glucose Metabolism: Glycolysis under Anaerobic Conditions

1. Overview

  • Glycolysis is the metabolic pathway that converts glucose (6C) into pyruvate (3C) or lactate, releasing energy in the form of ATP.
  • It occurs in the cytoplasm of all cells.
  • Under anaerobic conditions (absence of oxygen), pyruvate is converted into lactate instead of entering the mitochondria for oxidation.
  • Anaerobic glycolysis allows cells to produce ATP without oxygen, which is especially important for red blood cells, exercising skeletal muscle, and ischemic tissues.

2. Importance of Anaerobic Glycolysis

  • Provides rapid ATP when oxygen is limited.
  • Prevents accumulation of pyruvate and NADH by converting them to lactate and NAD⁺, allowing glycolysis to continue.
  • Plays a critical role in muscle contraction and RBC metabolism (which lack mitochondria).

3. Stages of Glycolysis (Anaerobic Pathway)

Glycolysis can be divided into two major phases:

(A) Energy Investment Phase

(B) Energy Generation Phase

A. Energy Investment Phase

  • Phosphorylation of Glucose
  • Enzyme: Hexokinase (or glucokinase in liver).
  • Reaction: Glucose → Glucose-6-phosphate (G6P).
  • ATP consumed: 1 ATP.
  • Purpose: Traps glucose inside the cell.
  • Isomerization of G6P
  • Enzyme: Phosphoglucose isomerase.
  • Reaction: G6P → Fructose-6-phosphate (F6P).
  • Second Phosphorylation
  • Enzyme: Phosphofructokinase-1 (PFK-1).
  • Reaction: F6P → Fructose-1,6-bisphosphate (F1,6BP).
  • ATP consumed: 1 ATP.
  • This is the rate-limiting step of glycolysis.
  • Cleavage of F1,6BP
  • Enzyme: Aldolase.
  • Reaction: F1,6BP → Glyceraldehyde-3-phosphate (G3P) + Dihydroxyacetone phosphate (DHAP).
  • DHAP is then converted into G3P by triose phosphate isomerase, resulting in two molecules of G3P per glucose.

B. Energy Generation Phase

  • Oxidation and Phosphorylation of G3P
  • Enzyme: Glyceraldehyde-3-phosphate dehydrogenase.
  • Reaction: G3P + Pi + NAD⁺ → 1,3-Bisphosphoglycerate (1,3-BPG) + NADH + H⁺.
  • This is the only oxidation step in glycolysis.
  • NADH formed must be reoxidized to NAD⁺ for glycolysis to continue (by lactate dehydrogenase under anaerobic conditions).
  • First Substrate-Level Phosphorylation
  • Enzyme: Phosphoglycerate kinase.
  • Reaction: 1,3-BPG + ADP → 3-Phosphoglycerate (3PG) + ATP.
  • ATP generated: 2 ATP per glucose (since 2 G3P molecules).
  • This is substrate-level phosphorylation — direct formation of ATP without the electron transport chain.
  • Conversion to 2-Phosphoglycerate (2PG)
  • Enzyme: Phosphoglycerate mutase.
  • Reaction: 3PG → 2PG.
  • Dehydration Step
  • Enzyme: Enolase.
  • Reaction: 2PG → Phosphoenolpyruvate (PEP).
  • This step forms a high-energy compound (PEP).
  • Second Substrate-Level Phosphorylation
  • Enzyme: Pyruvate kinase.
  • Reaction: PEP + ADP → Pyruvate + ATP.
  • ATP generated: 2 ATP per glucose.
  • Another example of substrate-level phosphorylation.

4. Fate of Pyruvate under Anaerobic Conditions

  • In the absence of oxygen, pyruvate cannot enter the mitochondria for oxidation.
  • Enzyme: Lactate dehydrogenase (LDH).

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