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Four
of the six genetically-engineered steps in the hydrocortisone
biosynthetic pathway were catalyzed by a class of enzymes called
Cytochrome P450's. Here we take a breif look at what these enzymes
do and how they do it.
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Cytochrome P450
Enzymes
Cytochrome P450's are a class of enzymes that catalyze
addition of oxygen to steroids, fatty acids, vitamins, as well as foreign
toxins that are to be eliminated. Cytochrome P450 hydroxylases carry
out the following reaction:
Cytochrome P450
Hydroxylases:
- Are found in virtually every tissue, and proliferate
in the liver and intestines (to help detoxify blood before it reaches
the rest of the body).
- Contain heme, which is necessary to carry out its
redox reactions.
- Receive reducing equivalents from NADPH-Cytochrome
P450 reductase
- Bind hydrophobic substrates (e.g. steroids), then
split an O2 molecule, and adds one oxygen atom to the substrate, and
the other goes to water.
Stereospecifity
and Regiospecifity
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- Cytochrome
P450's react only on specifc carbons of a sterol. This is called
regiospecifity. For example CYP21A1 alters only C-21, and CYP17A1
alters only C-17
- P450's
are also stereospecific. Hydroxyl groups can be added either
above or below the plane of the molecule.
- Hydroxyl
groups that are added above the plane of the molecule are called
beta (
 -OH) and
below the molecule are called alpha ( -OH).
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6A: Two different cytocrome P450's add hydroxyl groups to different
carbons (regiospecicifity) and with opposite stereochemistry (stereospecicifity). |
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