L 22- Glycolysis

22 Cytosolic Respiration

Intended Learning Outcomes (ILOs)

  • By the end of this lecture, students will be able to:

    1. Correlate carbohydrate intake to production of energy.

    2. Deduce how energy production differs among different cells and cellular compartments.

    3. Correlate regulation of glycolysis to energy production.

What is Glycolysis?

  • Glycolysis is a sequence of reactions occurring in the cytoplasm that involves the oxidation of glucose into two molecules of pyruvic acid (3-carbon molecule) under:

    • Aerobic conditions, producing energy (in the form of ATP).

    • Anaerobic conditions, leading to lactate formation, also providing energy.

  • Importance of Glycolysis:

    • Its ability to function with or without oxygen makes glycolysis critical for specific cell types, especially Red Blood Cells (RBCs), which lack mitochondria.

    • During physical exertion, anaerobic glycolysis acts as the primary energy source for muscles.

    • Glycolysis serves as a preliminary step before the complete oxidation of glucose.

    • It supplies carbon skeletons for amino acid synthesis and contributes to glycerol for fat production.

Glycolysis Process Overview

  • Anaerobic Conditions:

    • NADH + H+ (at step 6) is re-oxidized into lactate, facilitating glycolysis without oxygen, resulting in a net gain of 8 ATP.

Clinical Implications

  • Pyruvate Kinase Deficiency:

    • A condition affecting mature RBCs that rely solely on glycolysis for ATP.

    • Results in decreased ATP production, leading to hemolytic anemia.

    • Severe cases may require regular blood transfusions, with severity based on enzyme deficiency level.

Regulation of the Glycolytic Pathway

  • Key regulatory enzymes are three irreversible ones:

    1. Hexokinase

    2. Phosphofructokinase (PFK-1)

    3. Pyruvate Kinase (PK)

A. Hormonal Regulation:

  1. Covalent Modification:

    • Insulin: Active in the fed state, activates key glycolytic enzymes through dephosphorylation.

    • Glucagon: Active in fasting, inhibits key glycolytic enzymes through phosphorylation.

  2. Induction/Repression:

    • Insulin induces key glycolytic enzymes, while glucagon represses them.

B. Allosteric Regulation

Inhibitors of Glycolysis

  1. Mercury:

    • Inhibits glyceraldehyde-3-P dehydrogenase by binding to the enzyme's active site, halting glycolysis and causing cell death.

    • Common cause of mercury poisoning: consumption of contaminated seafood.

  2. Fluoride:

    • Combines with Mg2+ to form Mg fluoride; Mg is essential for enolase activity.

    • Interferes with enolase activity, hence its use as a rodenticide and pesticide.

    • FDA warning on fluoride toothpaste: Seek medical help if more than the recommended amount is swallowed.

What Happens After Pyruvate Production?

  • Under aerobic conditions, pyruvate is transported to the mitochondria.

  • Pyruvate is then converted to Acetyl Co-A by the Pyruvate Dehydrogenase Complex (PDH).