Chapter 2 Enzymes and Energy • MHR 49substrate. The metabolic pathway can only be
restored if the substrate concentration is increased
so that the substrate is more likely to enter the
active sites than is the inhibitor. Penicillin is a
commonly used competitive inhibitor. It works by
bonding to the active site of transpeptidase, the
enzyme involved in bacterial cell wall construction.
When penicillin transpeptidase inhibits, a bacterial
cell cannot divide successfully, and infection
is prevented.
Protease inhibitors are a relatively new class of
competitive inhibitors that interfere with the normal
activity of protease enzymes. Molecular modelling
played a major role in the research and design of
effective protease inhibitor molecules. Figure 2.12
shows the general appearance and behaviour of
protease and protease inhibitors. These inhibitors
have been used to dramatically reduce the level of
human immunodeficiency viruses (HIVs) in AIDS
patients. HIVs infect host cells, such as the T-cells
of the human immune system. The virus does this
by injecting its genetic material into the host cell.
The virus DNA then commandeers the cell’s
cellular processes to make polyproteins. The
protease HIV enzyme then cuts these polyproteins
into smaller structural proteins and enzymes that
will be used to make new HIVs. The snipping or
cleavage of polyproteins involves a hydrolysis
reaction that uses a water molecule for every bond
that is broken in the substrate molecule.
HIV protease inhibitors are similar in chemical
composition and structure to the HIV polyprotein.
The inhibitor molecules bind tightly to the active
site of HIV protease enzymes. This process
prevents the enzymes from cutting the actual HIV
polyproteins to form new HIVs. The HIV protease
enzyme is composed of two identical peptide
halves. The enzyme’s active site is located in the
depression formed where the two halves join.Cofactors and Coenzymes:
Non-protein Helpers
The final manner in which enzymes are regulated
comes in the form of cofactors. Cofactors are
inorganic ions and organic, non-protein molecules
that help some enzymes function as catalysts. The
inorganic ions are metals such as copper, zinc, or
iron. Located in the active sites of enzymes, these
ions attract electrons from substrate molecules. For
instance, carboxypeptidase breaks down proteins
using a zinc cofactor. This cofactor draws electrons
away from bonds, which causes them to break. If
cofactors are organic, non-protein molecules, they
are also called coenzymes. Many vitamins, small
organic molecules that the human body requires in
trace amounts to function, are parts of coenzymes.A B
C D
Figure 2.12
Protease and protease
inhibitor molecules.
(A) Polyprotein blocked
from the active site of a
protease enzyme by a
protease inhibitor molecule.
(B) Protease enzyme
approaching an HIV
polyprotein.
(C) Polyprotein that has
been split by the protease
enzyme.
(D) Polyprotein within
the active site of a
protease enzyme.