Enzymes — Chapter 5 Notes

Overview

  • Enzymes are, as reviewed, typically proteins that speed up biochemical reactions and are highly specific for particular reactions.
  • In glycolysis, there are 10 different reactions each with a distinct enzyme name, illustrating enzyme specificity.
  • Example: glucose to glucose-6-phosphate is catalyzed by hexokinase; the substrate is consumed and converted, while the enzyme remains unchanged and is not consumed in the reaction.

Key concepts and terminology

  • Substrate (S): the reactant in an enzyme-catalyzed reaction; a substrate is a starting material for that specific reaction. It is a type of reactant, but not every reactant is a substrate.
  • Product (P): what the substrate is transformed into during the reaction.
  • Enzyme (E): the catalyst, usually a protein, that speeds up the reaction without being consumed. The enzyme itself is left unchanged after the reaction.
  • Enzyme-Substrate complex (ES): the transient complex formed when the enzyme binds to its substrate at the active site.
  • Active site: the region of the enzyme where the substrate binds; the site has a shape complementary to the substrate to form the ES complex.
  • Substrate vs reactant distinction: substrate is the starting material in an enzyme-catalyzed step; a reactant is any starting material in any chemical reaction, but only some reactants are substrates in enzyme-catalyzed processes.
  • Holoenzyme: the complete, active form of an enzyme consisting of a protein plus a non-protein accessory component.
  • Cofactor: the non-protein component required for some enzymes to function; cofactors are not substrates or products.
    • Cofactors can be inorganic (metals) or organic (coenzymes).
  • Cofactor examples (inorganic): Fe, Cu, Ni, Mg, Mn, Zn, etc. These metals often serve as cofactors in various enzymes.
  • Organic cofactors (coenzymes): organic molecules that assist enzymes; one example is NAD/NADH, which functions as an electron carrier. NADH has one more hydrogen than NAD.
  • Ribozymes: enzymes made of RNA rather than protein (rare in biology).
  • Enzyme activity: a measure of how fast an enzyme speeds up a chemical reaction.
    • If enzyme activity is zero, the enzyme is not active and does not speed up the reaction.
    • If enzyme activity is high, the enzyme is very active and accelerates the reaction more rapidly.

Enzyme-catalyzed reactions: the mechanism

  • Long-form representation: E + S ⇌ ES → E + P
    • E + S forms the ES complex (binding is temporary).
    • ES leads to the formation of the product P, while the enzyme E is regenerated (not consumed).
    • The substrate is converted into product; the enzyme remains unchanged.
  • Short-form representation (common in textbooks): Substrate gets converted into product; the enzyme name is written above the arrow.
    • Example in glycolysis: Glucose (substrate) → Glucose-6-phosphate (product) with hexokinase (enzyme) acting above the arrow, illustrating the catalyzed step.

Example: sucrase-catalyzed reaction (from the figure)

  • Substrate: sucrose (a sugar)
  • Enzyme: sucrase (note the -ase suffix, common for enzymes)
  • Enzyme-Substrate complex: ES forms when sucrose binds to sucrase at the active site.
  • Products: glucose + fructose
  • Active site: the region on sucrase that binds sucrose; the substrate fits into this site, forming ES.
  • Induced fit concept: the substrate appears to fit like a puzzle piece, but the fit is slightly stressed; the bond is adjusted to facilitate the reaction. This destabilizes the substrate bonds, lowering the activation energy and increasing the reaction rate.
  • Key takeaway: E remains unchanged through the reaction; S is converted to P; ES is a transient intermediate.
  • Visualization note: the bond depicted as a straight line (in the substrate) becomes curved upon binding due to induced fit, illustrating the conformational change.

Active site and induced fit

  • Active site is the physical location on the enzyme where the substrate binds to form ES.
  • Induced fit: binding causes conformational adjustments; the fit is not perfectly static; the induced strain helps destabilize bonds and lowers the activation energy, speeding up the reaction.
  • Activation energy concept (referenced from earlier in the course): the energy barrier that must be overcome for a reaction to proceed; enzymes lower this barrier via ES formation and induced fit.

Enzyme structure: holoenzyme, cofactors, and ribozymes

  • Not all enzymes are pure proteins; some require non-protein components to be functional.
  • Holoenzyme: complete enzyme consisting of the protein component plus its non-protein cofactor
  • Cofactor: non-protein component essential for enzyme activity; not a substrate or product
    • Types of cofactors:
    • Inorganic cofactors: metals (e.g., iron, copper, nickel, magnesium, manganese, zinc)
    • Organic cofactors: organic molecules; often called coenzymes; example NAD/NADH as a coenzyme
  • NAD/NADH example: organic coenzyme; NADH has one more hydrogen than NAD, enabling electron transfer in metabolic reactions
  • Coenzyme vs cofactor terminology: coenzymes are a subset of cofactors (organic cofactors); not all cofactors are organic
  • Ribozymes: enzymes composed of RNA rather than protein (rare in biology)

Relationship to glycolysis and real-world relevance

  • In glycolysis, each of the 10 steps has a distinct enzyme name, illustrating enzyme specificity and the concept of enzyme-catalyzed reaction sequences.
  • Enzyme specificity ensures that only the intended reaction occurs at each step, enabling tight regulation of metabolism.
  • The concept of active sites, ES complexes, and induced fit underpins how enzymes recognize substrates and facilitate chemical transformations efficiently.

Summary of core points to remember

  • E + S ⇌ ES → E + P represents the catalytic cycle: binding to form ES, catalytic transformation to P, and release of P with E regenerated.
  • Substrate (S) is the starting material for an enzyme-catalyzed reaction; substrate is a specific type of reactant.
  • The active site is the binding region on the enzyme that provides specificity for the substrate.
  • Induced fit explains how binding strains substrate bonds to lower the activation energy and speed up the reaction.
  • Enzymes can be pure proteins or holoenzymes (protein + non-protein cofactors).
  • Cofactors are inorganic or organic; coenzymes are organic cofactors such as NAD/NADH.
  • Some enzymes are ribozymes (RNA enzymes).
  • Enzyme activity is a measure of how fast an enzyme speeds up a reaction; zero activity means no catalysis, high activity means rapid catalysis.

Quick references and formulas

  • Enzyme-catalyzed reaction representation:
    • E+SESE+PE + S \rightleftharpoons ES \rightarrow E + P
    • SEPS \xrightarrow{E} P (overall shorthand: substrate becomes product with enzyme on the arrow)
  • Conceptual statements to memorize:
    • The substrate is converted into the product; the enzyme is not consumed or permanently altered.
    • The active site is the binding location for the substrate on the enzyme.
    • Induced fit can destabilize bonds to lower the activation energy and accelerate the reaction.

Next steps mentioned in the lecture

  • The upcoming discussion will cover factors that influence enzyme activity (e.g., temperature, pH, inhibitors, activators) and how these factors regulate metabolic pathways.