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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?