Glycolysis in different tissues

Glycolysis in different tissues

Glycolysis in different tissues

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Glycolysis Regulation - The On/Off Switches

Key irreversible enzymes serve as control points:

  • Hexokinase/Glucokinase:
    • Hexokinase (most tissues): Inhibited by its product, Glucose-6-P.
    • Glucokinase (liver, pancreas): Induced by insulin.
  • PFK-1 (Rate-Limiting Step):
    • Activators: AMP, Fructose-2,6-bisphosphate.
    • Inhibitors: ATP, Citrate.
  • Pyruvate Kinase:
    • Activator: Fructose-1,6-bisphosphate (feed-forward).
    • Inhibitors: ATP, Alanine.

⭐ Citrate, a TCA cycle intermediate, allosterically inhibits PFK-1. This signals that the cell has abundant energy, halting glycolysis.

Liver vs. Muscle - A Tale of Two Tissues

  • Primary Goal & Location:
    • Liver (Hepatocytes): Clear blood glucose post-meal for storage (glycogen, fatty acids). Acts only when glucose is high.
    • Muscle (Myocytes): Provide ATP for contraction, ensuring glucose uptake even when blood levels are low.
FeatureLiverMuscle & Most Tissues
Key IsozymeGlucokinase (Hexokinase IV)Hexokinase I/II
Affinity ($K_m$)Low (High $K_m$, ~10 mM)High (Low $K_m$, <0.1 mM)
Capacity ($V_{max}$)High (avoids trapping glucose at low levels)Low (saturates quickly)
InhibitionBy Fructose-6-PhosphateBy Glucose-6-Phosphate (product)
Hormonal ControlSynthesis induced by InsulinNot induced by Insulin
PFK-1 Activator↑ Fructose-2,6-bisphosphate↑ AMP

⭐ In the liver, insulin activates the PFK-2 part of the bifunctional enzyme, producing Fructose-2,6-bisphosphate (F-2,6-BP). F-2,6-BP is a potent allosteric activator of PFK-1, committing glucose to glycolysis over gluconeogenesis.

RBCs, Brain & Cancer - The Specialists

  • Red Blood Cells (RBCs):

    • Rely exclusively on anaerobic glycolysis for all ATP (net 2 ATP/glucose).
    • Lack mitochondria, preventing oxidative phosphorylation.
    • A shunt produces 2,3-BPG, which decreases hemoglobin's $O_2$ affinity, aiding oxygen release to tissues.
  • Brain:

    • Primarily fueled by glucose; glycolysis is the mandatory first step before aerobic respiration.
    • Maintains a very high, constant glucose demand.
  • Cancer Cells (Warburg Effect):

    • Exhibit "aerobic glycolysis": a high rate of glycolysis even when $O_2$ is plentiful.
    • Generates lactate and provides biosynthetic intermediates to support rapid proliferation.

PET Scans exploit the Warburg effect. They use a glucose analog, Fluorodeoxyglucose (FDG), to visualize tumors, which have characteristically high glucose uptake.

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  • Red blood cells depend exclusively on anaerobic glycolysis for their ATP supply.
  • The liver uses glucokinase (a high-Km isozyme) to handle high glucose loads after meals.
  • In muscle, hexokinase (low-Km) ensures rapid glucose uptake for energy during contraction.
  • The brain has a constant, insulin-independent uptake of glucose to fuel its high metabolic rate.
  • Pyruvate kinase deficiency leads to hemolytic anemia by disrupting RBC metabolism.
  • The Warburg effect describes the reliance of cancer cells on aerobic glycolysis.

Practice Questions: Glycolysis in different tissues

Test your understanding with these related questions

A 45-year-old man is brought to the emergency department by ambulance after vomiting blood. The patient reports that he only ate a small snack the morning before and had not eaten anything for over 24 hours. At the hospital, the patient is stabilized. He is admitted to a surgical floor and placed on NPO with a nasogastric tube set to intermittent suction. He has been previously diagnosed with liver cirrhosis. An esophagogastroduodenoscopy (EGD) has been planned for the next afternoon. At the time of endoscopy, some pathways were generating glucose to maintain serum glucose levels. Which of the following enzymes catalyzes the irreversible biochemical reaction of this process?

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Flashcards: Glycolysis in different tissues

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Anaerobic glycolysis produces a net of _____ NADH per glucose molecule

TAP TO REVEAL ANSWER

Anaerobic glycolysis produces a net of _____ NADH per glucose molecule

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