4. Enzymes & Metabolism

MIT OpenCourseWare・2 minutes read

Today's lesson covers proteins, amino acids, and peptides, focusing on a protein variant causing sickle cell anemia, with genetic mutations affecting protein structure and function. Enzymes act as catalysts, manipulating reactions by lowering activation energy and impacting the energetics of transformations.

Insights

  • A single genetic mutation in the beta globin gene on chromosome 11 leads to sickle cell anemia by changing glutamic acid to valine, resulting in the sickling of red blood cells.
  • Enzymes, as proteins, act as catalysts in reactions by lowering the energy of activation, enabling changes and transformations at room temperature, and manipulating the energetics of reactions to facilitate various processes.

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Recent questions

  • What causes sickle cell anemia?

    Genetic mutation in hemoglobin.

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Summary

00:00

Proteins and Mutations in Sickle Cell Anemia

  • Today's lesson focuses on amino acids, peptides, and proteins, specifically discussing a protein variant causing sickle cell anemia.
  • Proteins' primary sequence determines their folded structure, with secondary and tertiary interactions playing crucial roles.
  • Some proteins form quaternary structures, like hemoglobin, which is a heterotetrameric protein.
  • Denaturation of proteins can occur due to factors like heat, pH changes, salt, organic solvents, and shear forces.
  • Denaturation through heat leads to irreversible protein unfolding and aggregation.
  • pH changes alter the charge states of amino acids, affecting protein structure.
  • Hemoglobin, a homotetrameric protein, carries oxygen and CO2 in red blood cells.
  • A single defect in beta globin, changing glutamic acid to valine, causes sickling of red blood cells in sickle cell anemia.
  • The genetic mutation causing sickle cell anemia involves a single base change in the beta globin gene on chromosome 11.
  • Understanding the structural and functional changes in proteins due to genetic mutations is crucial in diseases like sickle cell anemia.

15:59

"Sickle Cell Anemia: Hemoglobin Mutation Effects"

  • Hemoglobin carries oxygen in the blood and is found in erythrocytes.
  • Mutations in hemoglobin cause molecules to cluster and form long chains, leading to sickle cell shape.
  • Sickle cell shape causes red blood cells to clog in capillaries, resulting in pain and health issues.
  • The defect in hemoglobin affects how proteins interact, causing mechanical changes.
  • Sickle cell anemia is caused by a mutation in hemoglobin, resulting in hemoglobin S.
  • Heterozygous individuals have a mix of normal and sickle cell hemoglobin, manageable with care.
  • Homozygous individuals with the defect require transfusions and medical attention.
  • The mutation in hemoglobin causes interactions between subunits, leading to sickle cell formation.
  • Different amino acid variations can impact hemoglobin function, with some being less detrimental.
  • The sickle cell trait can provide resistance to malaria due to the shape of red blood cells.

31:53

"Enzymes: Catalysts for Energy-Efficient Reactions"

  • Enzymes are proteins that promote reactions, allowing them to occur at room temperature.
  • Enzymes enable changes and transformations in reactions due to their protein structure.
  • Thermodynamics and kinetics of a transformation are crucial to understanding enzyme function.
  • Gibbs free energy (delta G) is a key parameter in energy diagrams for reactions.
  • Enthalpy describes all bonds in a molecule, but enzymes focus on free energy changes.
  • Enzymes manipulate the energetics of reactions by lowering the energy of activation.
  • Exergonic reactions release energy, while endergonic reactions require energy.
  • Catabolic reactions produce energy, while anabolic reactions require energy for storage.
  • Enzymes act as catalysts, lowering the energy of activation and remaining unchanged after reactions.
  • Enzymes manipulate processes by orienting substrates, causing strain in bonds, and stabilizing charged intermediates.

48:45

Protein Data Bank: Slides Handout Available

  • Visit the Protein Data Bank site for more information.
  • Access a handout related to the slides on the site.
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