Download A Crash Course on Enzymology

A Crash Course on Proteins and
Drugs
Zachary Woydziak, Ph.D.
Chem 377
What are Proteins?
• Meat, internal organs, eggs – but these are only rich
in proteins.
• Proteins are any molecules composed of 40 or more
amino acids.
• Tons of these in the body and depending on the
amino acids making them they behave differently.
• Can also be modified to contains other moieties
such as metal ions or other molecules as to allow
the protein to perform a function.
What are Enzymes?
This reaction is normally quite slow…
But with the enzyme Carbonic Anhydrase
it is occurs almost instantaneously …
• Proteins that are catalysts for chemical
reactions in an organism.
• Without enzymes life could not be
possible as the bioreactions would be too
slow for life to exist.
• Example: Carbonic Anhydrase
What are Ligand Gated Ion Channels?
• Proteins that allow ions (Na+, K+, Ca2+, Cl- and etc.) to flow
across a membrane.
• “Ligand Gated” require a substrate (or ligand) to bind for
the channel to allow ions through (there is also “voltage
gated” which don’t require a substrate).
• Example: Nicotinic acetylcholine receptors – bind
acetylcholine to allow Na+ and K+ through. Neuroreceptor
and nicotine also binds!
What are Hormone Receptors ?
• A protein on the surface of a cell that binds to a specific
hormone.
• This then usually creates a cascade of events that ultimately
causes the cell to do something.
• Cascades make hormones quite powerful, since one
hormone can produce thousands if not millions of
messengers.
Some Questions for You!
A. Label following as being a protein or non-protein:
1.
2.
3.
4.
5.
6.
A string of 39 amino acids tethered by peptide bonds Not a protein
An Enzyme (generally) Protein
A ligand gated ion channel Protein
A ligand Not a protein
A hormone Not a protein
A piece of beef jerky Mostly Protein
B. Ligand gated ion channels require the binding of a __________
ligand to allow
____________
to pass through a membrane.
ions
C. The sole purpose of enzymes is to … for reactions in an organism:
a. Decrease the Gibbs free energy
c. Catalyze
b. Decrease Gibbs free energy
d. Decrease the activation Energy
Trick question!
Lock and Key Model
• Different Enzymes, composed of different
amino acids, perform different reactions.
• In some ways, a substrate(s) or molecule the
enzyme catalyzes a reaction on is like key that
only fits a certain lock (which is the enzyme).
• Consequently, it is the 3D shape that defines
and enzyme and makes it specific for a certain
substrate.
Protein Folding to make the “Lock” (Possibly
Remove)
• In the body proteins are assembled from amino
acids.
• These long strands of amino acids then fold by
hydrogen bonding and dipole-dipole interactions to
give a 3D shape (which is formed almost every time
to the correct shape!).
• The 3D shape is then a perfect fit for the substrate.
A Drug = Another Key that Works
• Just like not every lock is open just one key, not every
protein only binds one molecule.
• Drugs mimic the shape of a substrate which can have 2
effects on an enzyme, ion channel, hormone receptor, etc:
1. They can “jam up” the site of action and prevent the
normal substrate from binding … this is called inhibition.
2. They can promote the enzyme to work better which is
called activation.
Side Effects of Drugs
A drug can act like a skeleton key
And bind to many proteins
Resulting in side effects….
• Unfortunately, some keys can open multiple lock,
drugs can sometimes bind to multiple proteins.
• This causes undesired side effects.
• An ideal drug minimizes these, but from natures
standpoint sometimes multiple targets is a good
thing … like in the case of a toxin.
A Common Scenario
Dwight Kurt Schrute III is studying a pill that is used for hair
loss. In certain “investigative” studies he secretly sneeks
pills into the coffee of Kevin Malone and Todd Packer. After
week of such studies Dwight notices that both Kevin and
Todd have not gained any hair, but Todd has started to
sweat profusely … all of the time. Kevin appears to be
unaffected. What could be a cause why Todd is affected
but Kevin isn’t?