Download Non-competitive

Apoenzyme – the polypeptide portion of an enzyme
Cofactor – non protein portion of an enzyme
May be a metal ion such as Zn2+ of Mg2+
May also be an organic molecule such as
vitamin B or heme – called a coenzyme
Substrate – the molecule an enzyme acts on
Activation – any process that initiates or increases
the action of an enzyme
Inhibition – any process that inactivates an enzyme
or reduces its effectiveness
Competitive inhibitor – binds at the active
site
Non-competitive inhibitor – binds at other
than the active site
Enzyme Catalysis
• Enzyme: a biological catalyst
– with the exception of some RNAs that catalyze their own splicing,
all enzymes are proteins
– enzymes can increase the rate of a reaction by a factor of up to
1020 over an uncatalyzed reaction
– some catalyze the reaction of only one compound
( NH2 )C=O + H2 O urease
Urea
2NH3 + CO2
– others are stereospecific; for example, enzymes that catalyze the
reactions of only L-amino acids
– others catalyze reactions of specific types of compounds or
bonds; for example, trypsin that catalyzes hydrolysis of peptide
bonds formed by the carboxyl groups of Lys and Arg
Mechanism of Action
– both the lock-and-key model and the
induced-fit model emphasize the shape of
the active site
– however, the chemistry of the active site is
the most important
– just five amino acids participate in the
active sites in more than 65% of the
enzymes studies to date
– these five are His > Cys > Asp > Arg > Glu
– four these amino acids have either acidic
or basic side chains; the fifth has a
Enzyme Regulation
• Protein modification: the process of affecting enzyme
activity by covalently modifying it -
•
the best known examples of protein modification
involve phosphorylation/dephosphorylation
example: pyruvate kinase (PK) is the active
form of the enzyme; it is inactivated by
phosphorylation to pyruvate kinase
phosphate (PKP)
ATP
ADP
active
inactive
kinase
PK
PKP
phosphatase
Pi
Succinylcholine is a competitive inhibitor of acetylcholine at
receptors – it is broken down slowly by acetylcholinesterase. This
leaves the receptor blocked and the muscle relaxed.
Chem Connect 22A, p.555
Sulfa drugs are competitive inhibitors of p-aminobenzoic acid in
the synthesis of folic acid in bacteria
Chem Connect 22D, p.562
Enzyme Regulation
• Proenzyme (zymogen): an inactive form
of an enzyme that must have part of its
polypeptide chain cleaved before it
becomes active.
An example is trypsin, a digestive enzyme - it
is synthesized and stored as trypsinogen,
which has no enzyme activity. It becomes
active only after a six-amino acid fragment
is hydrolyzed from the N-terminal end of its
chain Removal of this small fragment
changes in not only the primary structure
but also the tertiary structure, allowing the
Enzyme Regulation
• Isoenzyme: an enzyme that occurs in
multiple forms; each catalyzes the same
reaction
Example: lactate dehydrogenase (LDH)
catalyzes the oxidation of lactate to
pyruvate The enzyme is a tetramer of H
and M chains. H4 is present predominately
in heart muscle. M4 is present
predominantly in the liver and in skeletal
muscle. H3M, H2M2, and HM3 also exist
– H4 is allosterically inhibited by high levels
of pyruvate while M4 is not. H4 in serum
correlates with the severity of heart