In-Depth Notes on Enzymes and Their Mechanism

Structure of Enzymes

  • Enzyme Basics
    • Enzymes are biological catalysts that speed up reactions by lowering the activation energy barrier.
    • Reactants convert to products either with or without the presence of enzymes.

Cofactors

  • Types of Cofactors:

    • Prosthetic Groups: Covalently bound to the protein (e.g., haem in haemoglobin).
    • Metal Ions: Can be ions like Zn²⁺ and Fe³⁺ that help in enzyme function.
    • Coenzymes: Often vitamin derivatives that assist in enzyme function.

  • Enzyme Classifications:

    • Apoenzyme: The protein part of an enzyme without its cofactor.
    • Holoenzyme: The complete enzyme with its cofactor and active site.

Active Site Characteristics

  • Active Site Structure:

    • A cleft or groove in the enzyme where substrate binding occurs.
    • Contains residues that bind the substrate and facilitate the catalytic reaction.

  • Complementarity:

    • The active site is complementary to the substrate in terms of size, shape, charge, and hydrophobicity.

Enzyme Mechanisms

  • Lock and Key Model:

    • Proposed by Emil Fischer (1894) to explain enzyme specificity.
    • Active site is seen as rigid; substrate fits exactly like a key fits a lock.
    • Limitations: Cannot explain enzyme action on a diverse range of substrates.

  • Induced Fit Model:

    • Proposed by Daniel Koshland (1959).

    • Suggests that the substrate induces a change in the enzyme structure, allowing a better fit.

    • Demonstrates that enzymes are flexible and can mold to fit substrate shapes, like a glove fits a hand.

    • Example: Hexokinase phosphorylates glucose to glucose 6-phosphate, with conformational changes upon glucose binding.

Domain Functionality

  • Enzyme Composition:
    • Some enzymes, like Phosphofructokinase 2 (PFK2), have different functional domains:
    • Kinase Domain: Adds a phosphate group.
    • Phosphatase Domain: Removes a phosphate group.

Isomer Production

  • Isomer Specificity:
    • Enzymes can produce only one isomer by distinguishing between chemically identical groups in a substrate by binding at multiple points.
    • Three-Point Attachment Model: The substrate binds at three or more points, which helps in distinguishing between isomers (e.g., Citrate and D-isocitrate in the case of Aconitase).

Key Models Comparison

  • Model Summaries:

    • Lock and Key Model: All about a fixed fit of substrate and enzyme.
    • Induced Fit Model: Enzyme modifies its shape to fit the substrate (dynamic interaction).
    • Three-Point Attachment Model: Explains how substrates bind in multiple places to ensure specificity.

  • The role of cofactors and coenzymes in enzyme function is crucial in facilitating various biochemical reactions.