Enzymatic

catalysis
 ENZYME CATALYSIS
• Enzymes achieve their enormous rate accelerations via the
same catalytic mechanisms used by chemical catalysts.
Enzymes, like other catalysts, reduce the free energy of the
transition state (AG); that is, they stabilize the transition state
of the catalyzed reaction.
 FREE ENERGY
• Free energy (G) is the most valuable thermodynamic function for
determining whether a reaction can take place and for
understanding the energetics of catalysis. A reaction can occur
spontaneously only if the change in free energy (A G) is negative.
Enzymes do not alter reaction equilibria; rather, they increase
reaction rates.
Enzyme catalyzed
reaction
BIOCHEMICAL MECHANISMS
The types of catalytic mechanisms that enzymes employ have been classified
as:
• Acid-base catalysis
• Covalent catalysis
• Metal ion catalysis
• Proximity and orientation effects
• Catalysis by approximation.
 • General acid catalysis is a process in which
proton transfer from an acid lowers the free
ACID- energy of a reaction's transition state. The
ionizable functional groups of amino acyl side
BASE chains and (where present) of prosthetic
CATALYSI groups contribute to catalysis by acting as
acids or bases. The ability of enzymes to
S arrange several catalytic groups around their
substrates makes concerted acid-base
catalysis a common enzymatic mechanism.
ACID- • The catalytic activity of these enzymes
is sensitive to pH, since the pH
BASE influences the state of protonation of
CATALYSI side chains at the active site. RNase A Is
S CONTD. an Acid-Base Catalyst.
pancreatic RNase A provides an
Bovine

example of enzymatically mediated

acid-base catalysis. This digestive
enzyme is secreted by the pancreas
into the small intestine, where it
nucleotides. hydrolyzes RNA to its
component
COVALEN • The process of covalent catalysis involves the
formation of a covalent bond between the
T enzyme and one or more substrates.
CATALYSI • Covalent catalysis accelerates reaction
ratesthrough the transient formation of a
S catalystsubstrate covalent bond.
• Usually, this covalent bond is formed by the
catalyst with an electrophilic group on the
substrate, and hence this form of catalysis is
often also called nucleophilic catalysis.
 • Covalent catalysis can be conceptually decomposed
into three stages:
• The nucleophilic reaction between the catalyst and
COVALEN the substrate to form a covalent bond.
• The withdrawal of electrons from the reaction center
T by the now electrophilic catalyst.
CATALYSI • The elimination of the catalyst, a reaction that is
S CONTD. essentially the reverse of stage 1.
COVALEN • Functional groups in proteins that act in this
way include:
T • The unprotonated amino group of Lysine,
CATALYSI • The imidazole group of Histidine
S CONTD. • The thiol group of Cysteine
• The carboxyl group of Aspartic acid, and the
hydroxyl group of Serine.
Example Covalent catalysis include the
proteolytic enzyme
chymotrypsin and trypsin in
which the nucleophile is the
hydroxyl group on the serine.
 • Nearly one-third of all known enzymes
require metal ions for catalytic activity. This
group of enzymes includes the
METAL metalloenzymes
ION • Most common transition metal ions include
Fe²+, Fe³+, Cu²+, Mn²+ or, Co²+
CATALYSI • lonic interactions between an enzyme-bound
S metal and a substrate can help orient the
substrate for reaction or stabilize it.
 • Metal ions participate in the catalytic
process in three major ways:
METAL • By binding to substrates to orient them
ION properly for reaction.
CATALYSI • By mediating oxidation-reduction
S reactions through reversible changes in
the metal ion's oxidation state.
• By electrostatically stabilizing or shielding
negative charges.
 • An excellent example of this phenomenon occurs in
the catalytic mechanism of carbonic anhydrase a
Example widely occurring enzyme that catalyzes the reaction:
• CO2 + H2O→HCO3 + H+
 • Enzyme-substrate interactions align the
reactive chemical groups and hold them close
together in an optimal geometry, which
increases the rate of the reaction.
PROXIMITY
• This reduces the entropy of the reactants and
AND thus makes addition or transfer reactions less
ORIENTATI unfavorable, since a reduction in the overall
ON entropy when two reactants become a single
product.
 • Many reactions include two distinct
substrates. In such cases, the reaction rate
may be considerably enhanced by bringing
CATALYSIS BY the two substrates together along a single
APPROXIMATI binding surface on an enzyme. NMP
kinases bring two nucleotides together to
ON facilitate the transfer of a phosphoryl
group from one nucleotide to the other.
This strategy takes advantage of binding
energy and positions the substrates in the
correct orientation for the reaction to
proceed.
 • An example of catalysis by
approximation is when NMP
Example kinases bring two nucleotides
together to facilitate the transfer
of a phosphoryl group from one
nucleotide to the other.