Enzymes

How do the DNA-coded proteins affect a cell?

Each molecule has a quantity of potential energy in its molecular structure. If that structure is disturbed then some potential energy may be converted into kinetic energy and released. Products with lower inherent potential energy are produced.

During a chemical reaction, the reactants must have sufficient energy to overcome an energy barrier, called activation energy. Collisions can increase the kinetic energy of molecules and provide that extra kick.

A + B		[AB]		AB*
Stable		Unstable		Stable
reactants		reactants		product

Net free energy is released during the reaction. Arrows indicate the favored direction of reaction, reverse requires more energy. The greater the activation energy, the slower the reaction rate. ^*Figure in class.

Heat, higher concentrations of reactants, or catalysts can increase number of collisions.

In cells many chemical reactions would be very slow at physiological body temperature. Adding heat would denature proteins and have other detrimental effects on the body. Cells cannot always provide higher concentrations of reactants. So what are catalysts?

Catalyst

substance that speeds up the rate of reaction but is not used up during the reaction, subdivides a large activation energy into several smaller steps

Enzyme

• Organic catalyst, usually a protein
• Doesn't start a reaction but increases reaction rate
  • By increasing local concentrations of reactants
  • By orienting reactant molecules
  • By directing reaction through different pathways with intermediates of lower activation energy ^*Figure in class.
  • Doesn't change net free energy release

Substrate

any substance acted upon by the enzyme & chemically modified, reactant

E + S1 + S 2

[S1ES 2]

E + S1S 2(product)

Active site

1. Surface location on the enzyme molecule where substrate attaches (domain) and is chemically modified
2. Function of specific structural organization of the protein, determined by tertiary and quaternary structure of protein
3. Enzymes are substrate-specific, because of the specific structure of the binding site only certain substrates can attach to any one enzyme
4. Two models explain substrate specificity:
   • Lock & Key model - enzyme active site and substrate have complementary shapes, most other substrates won't fit
   • Induced Fit model - shape of the active site changes to fit substrate after substrate is attached (allosteric change), allows for preferential selection of substrate isomers

Factors affecting enzyme activity

1. Activation - most proteins can shift reversibly between two different but stable structural configurations (allosteric).  For an enzyme one configuration has the active site, the other configuration does not
2. Temperature - increase or decrease reaction rate, but extremes denature proteins
3. pH - determines protein charge & shape.  Optimal pH range of enzyme activity
4. Increased concentrations - speeds up reaction rate in both directions but does not change equilibrium point for reaction.  Limited by enzyme saturation.  Substrate or product concentrations affect ratio of forward to backward rate of reactions
5. Multienzyme complexes - groups of enzymes involved in a sequence of reactions, product of one reaction is the substrate of the next reaction
6. Cofactors (ions) or coenzymes (organic nonprotein substances) bind to a protein to form the specific enzyme.  ex. heme, vitamins
7. Competitive inhibition - substance similar to substrate binds with enzyme and inactivates it temporarily (drugs) or permanently (insecticides)
8. Hormones - directly or indirectly activate or inactivate intracellular enzymes ex. Hormone attaches to receptor site on cell membrane and initiates reaction in membrane which produces cAMP within the cell, cAMP activates Enzyme₂ & inactivates Enzyme₁
   

   	E1
   glucose		glycogen (in muscle cell)
   	E2

9. Feedback regulation - product concentration affects production Figure in class