Ch 8 Metabolic Pathways and Feedback Inhibition

Metabolic Pathways and Feedback Inhibition

Enzymes and Metabolism

• Enzymes are vital, speeding up biological reactions.

• Metabolism: Sum of all chemical reactions in an organism.

• Metabolism regulated by enzyme activity.

Enzyme Regulation: Co-factors, Co-enzymes, and Prosthetic Groups

• Most enzymes require additional molecules for activation and substrate binding.

• Apoenzyme: Inactive enzyme.

• Holoenzyme: Active enzyme (apoenzyme + coenzyme/cofactor).

• Types of Regulatory Molecules:

  • Cofactors: Reversible inorganic activators (e.g., $Mg^{2+}$, $Zn^{2+}$).

  • Coenzymes: Loosely bound, reversible organic molecules; often electron carriers (e.g., $NADH$, $FADH_2$ in ATP synthesis).

  • Prosthetic Groups: Tightly/permanently bound organic molecules (e.g., heme).

• These molecules bind enzymes to control function, not part of primary structure.

• Mechanism: Determine active/inactive form, change 3D structure, alter substrate affinity.

Enzyme Regulation: Covalent Modifications

• Covalent modifications: Reversible or irreversible binding to enzyme's primary structure.

• Irreversible: Less common, typically permanent activation/inactivation via peptide bond cleavage.

• Reversible: Common, vital for dynamic regulation.

• Phosphorylation: Addition of a phosphate group ($PO_4^{3-}$).

  • Switches enzyme between active/inactive states.

  • Induces conformational shift, altering substrate affinity.

• Kinases: Add phosphate groups.

• Phosphatases: Remove phosphate groups.

• Effect: Phosphate addition/removal changes enzyme shape, activating/inactivating it.

Enzyme Regulation: Non-Covalent Modifications

• Non-covalent modifications: Temporary, reversible, do not permanently alter enzyme structure.

• Competitive Inhibition:

  • Molecule similar to substrate competes for active site.

  • Inhibitor binding blocks substrate, preventing reaction.

  • Inhibitor can dissociate, allowing reaction to proceed.

• Allosteric Regulation:

  • Molecule binds to allosteric site (not active site).

  • Changes enzyme's overall shape, altering active site.

  • Non-competitive inhibition:

    • Allosteric binding deactivates enzyme by changing active site shape.

    • Substrate cannot bind; inhibitor doesn't compete for active site.

    • Inhibitor dissociates, active site returns to normal, reaction resumes.

  • Allosteric activation:

    • Regulatory molecule binds to allosteric site.

    • Changes active site to facilitate substrate binding.

    • Enzyme inactive without activator.

Metabolic Pathways

• Definition: Series of interconnected reactions to synthesize biological molecules.

• Each step catalyzed by a specific enzyme.

• Concept from one gene-one enzyme hypothesis (e.g., arginine synthesis).

• Pathway example:

  • $E_1$ binds precursor $o$ Intermediate A.

  • $E_2$ converts Intermediate A $o$ Intermediate B.

  • $E_3$ converts Intermediate B $o$ Final end product.

Feedback Inhibition

• Definition: End product inhibits an early enzyme in its own metabolic pathway.

• Purpose: Prevents overproduction and conserves resources by shutting down the pathway.

• Mechanism: Often via competitive or, more commonly, allosteric inhibition.

• Pathway example:

  • End product binds allosteric site on $E_1$.

  • Conformational change in $E_1$'s active site.

  • $E_1$ can no longer bind precursor substrate, shutting down pathway.

• Reversibility: End product removal (consumption/drop in concentration) detaches from $E_1$, restoring active site and restarting pathway, ensuring activity only when needed.