52 MHR • Unit 1 Metabolic Processes
DNA can play a role in determining whether or
not an individual’s enzymes are functioning
normally. For example, Hurler syndrome is a
genetic disorder caused by a defective gene. A child
born with Hurler syndrome cannot manufacture
the enzyme alpha-L-iduronidase. This enzyme is
one of 10 lysosomal enzymes responsible for
breaking down complex carbohydrates called
mucopolysaccharides (MPS). Mucopolysaccharides
are largely responsible for building connective
tissues in the human body. If mucopolysaccharides
cannot be broken down properly, they build up in
body cells and form excess tissue. A child diagnosed
with Hurler syndrome will become afflicted with
various cardiac or respiratory ailments by the age
of five and not survive long thereafter.People have also found ways to exploit enzymes
and coenzymes for industry and profit. One of the
most obvious ways that enzymes can be used in
industry is in wine-making. Before 1897, scientists
believed that enzymes required living material to
function. The first to discover that a cell-free, or
non-living, extract of yeast could cause alcohol
fermentation was the German chemist Eduard
Buchner (shown in Figure 2.13). His experiments
led to the use of enzymes in industries as diverse
as wine production, leather tanning, food
production, textiles, pulp and paper, and
pharmaceutical manufacturing.Enzymes are essential to the pharmaceutical
industry in making products — from chemotherapy
treatments to common painkillers. Many of these
products are composed of enzymes or make use of
enzymatic reactions. As well, they often affect the
activity of enzymes within the body. A new form of
chemotherapy, Antibody-directed Enzyme Prodrug
Therapy (ADEPT) uses enzymes to improve the
efficiency of the drugs being used in the treatment
of common solid tumours. This process involves
using tumour-associated antibodies directed against
tumour antigens. Doctors link the antibodies to
enzymes and administer them to the patient. A
prodrug is administered separately. A prodrugis an
inactive drug that is only converted into its active
form in the body by metabolic activity. At the site
of the tumour, the enzyme converts the prodrug
into an active compound that is toxic to the tumour.
Painkillers, for example, affect enzymes in order
to relieve headaches, inflammation, or swollen
tissues. Aspirin™ and similar painkillers reduce
inflammatory pain by inhibiting enzymes called
cyclo-oxygenase (Cox) 1 and 2. Cox-1 is located in
the stomach, protecting it from hydrochloric acid
in the digestive juices. Cox-1 is also found in blood
platelets, where it aids in clotting reactions.
Cox-2 is produced in the skin or joints following
inflammation. Cox-2 is necessary in catalyzing the
formation of prostaglandin E2 (PGE2), which
increases the sensitivity of nerves to pain.
Until recently, biochemists believed that
inhibition of PGE2 at the site of inflammation
accounted for both the anti-inflammatory and
painkilling actions of Aspirin™ and similar
painkillers. Although Cox-2 is produced at the
inflamed site of the body, recent studies have
shown that nerve cells in the spinal cord and brain
also begin to produce it. This results in the
production of PGE2 throughout the central nervous
system. Biochemists revised their knowledge of
how and where Aspirin™ works. Aspirin™
reduces inflammatory pain not only at the inflamed
site but also in the entire central nervous system.
Because PGE2 increases nerve sensitivity to pain,
its manufacture throughout the central nervous
system accounts for the tenderness surrounding
inflamed tissues. Researchers suspect that the
presence of Cox-2 and PGE2 may explain why
people with inflamed tissues experience aches
and pains and even appetite loss and depression.
Figure 2.13Chemist
Eduard Buchner
(1860–1917)http://www.mcgrawhill.ca/links/biology12
To find out more about the kinds of symptoms associated with
MPS disorders, go to the web site above, and click on Web
Links. Why might a buildup of mucopolysaccharides cause
such symptoms? What kinds of treatments have been found
to alleviate the symptoms of Hurler syndrome? Prepare a brief
report of your findings.