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Lecture 4

BIOL 200 Lecture Notes - Lecture 4: Xeroderma Pigmentosum, Glycogen Synthase, Cholinesterase

Biology (Sci)
Course Code
BIOL 200
Mathieu Roy

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Enzyme production (transcription and translation of enzyme genes) can be enhanced or
diminished by a cell in response to changes in the cell's environment. This form of gene
regulation is called enzyme induction and inhibition. For example, bacteria may become resistant
to antibiotics such as penicillin because enzymes called beta-lactamases are induced that
hydrolyze the crucial beta-lactam ring within the penicillin molecule. Another example are
enzymes in the liver called cytochrome P450 oxidases, which are important in drug metabolism.
Induction or inhibition of these enzymes can cause drug interactions.Enzymes can
be compartmentalized, with different metabolic pathways occurring in different cellular
compartments. For example, fatty acids are synthesized by one set of enzymes in
the cytosol,endoplasmic reticulum and the Golgi apparatus and used by a different set of
enzymes as a source of energy in the mitochondrion, through β-oxidation. Enzymes can be
regulated by inhibitors and activators. For example, the end product(s) of a metabolic pathway
are often inhibitors for one of the first enzymes of the pathway (usually the first irreversible step,
called committed step), thus regulating the amount of end product made by the pathways. Such a
regulatory mechanism is called a negative feedback mechanism, because the amount of the end
product produced is regulated by its own concentration. Negative feedback mechanism can
effectively adjust the rate of synthesis of intermediate metabolites according to the demands of
the cells. This helps allocate materials and energy economically, and prevents the manufacture of
excess end products. The control of enzymatic action helps to maintain a stable internal
environment in living organismsEnzymes can be regulated through post-translational
modification. This can include phosphorylation, myristoylation and glycosylation. For example,
in the response to insulin,the phosphorylation of multiple enzymes, including glycogen synthase,
helps control the synthesis or degradation of glycogen and allows the cell to respond to changes
in blood sugar. Another example of post-translational modification is the cleavage of the
polypeptide chain. Chymotrypsin, a digestive protease, is produced in inactive form
as chymotrypsinogen in the pancreas and transported in this form to the stomach where it is
activated. This stops the enzyme from digesting the pancreas or other tissues before it enters the
gut. This type of inactive precursor to an enzyme is known as a zymogen.Some enzymes may
become activated when localized to a different environment (e.g., from a reducing (cytoplasm) to
an oxidizing (periplasm) environment, high pH to low pH, etc.). For example, hemagglutinin in
the influenza virus is activated by a conformational change caused by the acidic conditions, these
occur when it is taken up inside its host cell and enters the lysosome.
Since the tight control of enzyme activity is essential for homeostasis, any malfunction
(mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to
a genetic disease. The importance of enzymes is shown by the fact that a lethal illness can be
caused by the malfunction of just one type of enzyme out of the thousands of types present in our
bodies.One example is the most common type of phenylketonuria. A mutation of a single amino
acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation
of phenylalanine, results in build-up of phenylalanine and related products. This can lead
to mental retardation if the disease is untreated. Another example of enzyme deficiency
is pseudocholinesterase, in which there is slow metabolic degradation of exogenous
choline.]Another example is when germline mutations in genes coding for DNA repair enzymes
cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes
cause cancer since the body is less able to repair mutations in the genome. This causes a slow
accumulation of mutations and results in the development of many types of cancer in the
sufferer.Oral administration of enzymes can be used to treat several diseases (e.g. pancreatic
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