EFB325 Cell Physiology

Chemical reactions and equilibrium

How do we know what chemical reactions are possible?

• they need to have that destiny
• they need to have a path to that destiny

Destiny

First law of thermodynamics=energy cannot be created or destroyed

Second law of thermodynamics=universe becomes more disordered with every reaction

We describe the order of a molecule in terms of G=its free energy (capacity to do work)

• G is made up of the thermal energy contained in a molecule (H, enthalpy) and its degree of disorder (S, entropy)
• G=H-TdeltaS

For a particular reaction (in an open system), we need to compare the G of the reactants to the G of the products

• deltaG=G_products - G_reactants =change in free energy upon completion of the reaction

When deltaG is negative, then the free energy of the products is lower than the free energy of the reactants, and thus the universe will become more disordered

A reaction with negative deltaG is possible and spontaneous (it is destined to occur), but there must be a mechanism or pathway for that reaction to take before it will occur

The standard free energy change (deltaG^o) represents the release of free energy when 1 mole of reactant (A) is converted to 1 mole of product (B) (under standard temperature and pressure)

Predicting destiny

The amounts of reactant and product are rarely going to be 1 mole each, so how do we predict how a reaction will proceed based on the amounts of reactant and product?

A reaction will always proceed toward an equilibrium point where the system is in its lowest energy state

We can predict whether a reaction will proceed by comparing it to an equilibrium constant

• In the reaction of A -> B; K_eq=[B]/[A] when the reaction has come to equilibrium
• at equilibrium, there is no net change in energy

When the prevailing concentrations of reactant and product are different than the equilibrium concentrations, then there is some level of potential free energy, which would be released as the reaction goes toward equilibrium

• for example, if the K_eq =3 and the prevailing concentration of A is 20 mM and of B is 5 mM, then the reaction can go forward
• if the prevailing concentration of A is 1 mM and of B is 10 mM, then the reaction will tend to go backwards, converting B to A

BOTTOM LINE: by continuously varying reactant and product concentrations, we can always keep a reaction progressing toward equilibrium (toward its destiny), as long as it has a path!

• The concentrations might be varied by either adding more reactant or removing product (as in sequential reactions in a pathway)

Coupled reactions

A reaction with a positive deltaG can be coupled to another reaction with a negative deltaG, so that the net deltaG is negative

Path to destiny

The free energy calculations above only compare the energies of products and reactants

• if deltaG is negative, then the reaction is possible
• BUT there is a barrier preventing that from happening, the activation energy
• the reactant molecules must have a certain amount of additional kinetic energy for the reaction to occur

To encourage a reaction to occur, we can either:

• increase the amount of energy in the reactants (add heat)
• or decrease the activation energy (use a catalyst)

Enzymes are catalysts:

• they participate in the reaction, but are not changed when it is completed
• do not affect the balance of the equilibrium, only the rate at which equilibrium is reached
• specific for the reaction (unlike adding heat); rate=10⁸ - 10¹⁰-fold faster
• reduce the activation energy by bringing the reactants into position that facilitates reaction (form a transient complex)

Enzymes most commonly are proteins (name them by adding -ase, i.e. cellulase), but RNA can also catalyze reactions=ribozymes

The reactant in an enzymatic reaction=substrate

• substrate binds to an active site-usually very specific pocket within the folded shape of a protein
• protein changes shape a little when substrate binds, stresses bonds, puts atoms adjacent to reactive amino acids or prosthetic group (like an Fe atom) in the protein

Increased temperature increases the rate of the reaction (due to increased energy), but ...

• enzymes have an optimum temperature (before they are denatured)
• and an optimum pH (at which R-groups are protonated or deprotonated)

Enzymes are catalysts:

• they participate in the reaction, but are not changed when it is completed
• do not affect the balance of the equilibrium, only the rate at which equilibrium is reached
• specific for the reaction (unlike adding heat); rate=10⁸ - 10¹⁰-fold faster
• reduce the activation energy by bringing the reactants into position that facilitates reaction (form a transient complex)

Regulation

Reactions in the cell are regulated by regulation of enzyme activity

• the amount or compartmentation of enzyme can be regulated
• more commonly, the catalytic activity of existing enzyme molecules can be varied

Enzyme activity is sensitive to temperature and pH, which can alter the chemical interactions responsible for maintaining 3-D structure and substrate binding

Enzymes often bind another molecule in addition to the substrate

• binding at a regulatory site
• may act as an inhibitor or as an activator
• binding of another molecule often causes a slight change in the shape of the enzyme, altering its activity=allosteric regulation
• often the final product of a pathway will act to inhibit an enzyme that catalyzes an early step in the pathway=feedback inhibition

Addition or removal of a phosphate group to one or more amino acids (usually Ser, Thr, Tyr, or His) in an enzyme can alter its activity

• addition of a phosphate group=phosphorylation and is catalyzed by enzymes called kinases
• removal of a phosphate group=dephosphorylation and is catalyzed by enzymes called phosphatases

Thus, the activity of an enzyme (even a kinase or phosphatase) can be regulated by the activity of another enzyme (a kinase or phosphatase)

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