What is the difference between a reversible enzyme inhibitor and an irreversible enzyme inhibitor? Reversible are not permanent while irreversible are permanent. This means that a reversible inhibitor simply sits in the active site while the irreversible inhibitor covalently binds to the enzyme. --What is the difference between a receptor agonist and antagonist? An agonist binds to the receptor just like the natural NT, forcing it tochange shape, and sends the signal to the interior of the cell. An antagonist binds to the receptor but does not force the receptor to change its shape, thus no activity occurs inside the cell. --Which type of inhibitor is aspirin? & Which enzyme does aspirin inhibit Aspirin inhibits the cyclooxygenase (COX) enzymes by covalently reactingwith a serine (- OH) in the active site. More specifically, the ester group of aspirin gets attacked by the OH. Thus aspirin is an irreversible inhibitor. Recently it has been discovered that there are 3COX enzymes and it is COX- 2 that is mostly responsible for the production of prostaglandins. The over production of prostaglandins is one cause of inflammation and ultimately pain. Aspirin is not specific forCOX-2 and thus some people have adverse reactions to aspirin. Some newerdrugs inhibit COX-2 and thus are not as likely to produce side effects. --How does the binding of a NT to its receptor protein transmits a signal to the inside of a cell?When a NT binds to a receptor protein outside the cell, the protein is forced to change its shape. This shape change causes the molecules inside the cell to do “get into gear” and do something. --How do sulfanilimides and penicillin attack bacteria? i.e. in what ways are bacterial cells different from human cells?Sulfanilimides inhibit an enzyme (dihydropteroate synthetase) that bacterial cells have but human cells do not.Bacteria need folic acid to survive and sulfanilimides inhibit the enzyme that is responsible for the synthesis of folic acid. One of the substrates for the enzyme is gamma-amino-butyric acid (GABA) and the sulfanilamide resembles the GABA. Sulfanilimide occupies that same place as GABA in the active-site and thus it is a reversible inhibitor. Bacteria cells have cell walls while human cells have cell membranes. Cell walls are stronger because the sugar chains are covalently connected (cross-linked) via short peptides. Membranes are composed of phospholipid tails that are not covalently linked. Penicillin inhibits the enzyme (transpeptidase) that connects the peptides between the sugar chains. And, if the bacterial cell wall is not cross-linked, the cell will not survive. --Structure-Activity Relationship: The relationship between the chemical or 3D structure of a molecule and its biological activity)Penicillin is one of the first drugs to be studied. This is because synthetic organic chemistry had evolved to the stage where we could synthesize variations of the natural product. Thus chemists synthesized versions of penicillins where all of the functional groups were altered from the natural version. --How have bacteria been able to resist our anti-bacterial drugs such as penicillin? And how has the medical community responded to these drug-resistant bacteria? The bacteria have created enzymes (B-lactamases) that cleave the 4-membered ring amide bond of the penicillin so that the drug is no longeractive. The medical community has fought back by adding B-lactamase inhibitors to the penicillin (common version is Augmentin), so that the B-lactamase enzyme is inhibited and the drug is remains active. --Illustrate the “life-cycle” of the NT acetylcholine.1) synthesis of acetylcholine 2) acetylcholine goes to vesicle and is “shot” towards the receptor 3) acetylcholine binds to its receptor; “signal” is sent to the inside of cell 4) acetylcholine wanders over to the acetylcholineesterase (ACE) to be “chopped”5) the choline goes back to nerve cell and binds to receptor protein --How do we know there are at least two types of receptors for acetylcholine? In the nervous system, acetylcholine is found to bind all over the body and elicits different response. In general, the two types are classified as muscarinic and nicotinic. --How do the organophosphorous ACE inhibitors work? The organophosphorous ACE inhibitors (example: mustard gases) covalentlybind to the Ser (-OH) in the active-site of the enzyme. The fact that these agents are so deadly to humans illustrates the importance of acetylcholine and the acetylcholine cycle to our survival.--Why are the insecticides malathion and parathion active in plants but not humans? These insecticides have P=S instead of P=O. However, insects have an enzyme that can convert P=S to P=O and thus it can inhibit ACE in vivo. Humans do not the enzyme and thus our ACE is not inhibited. --How do the structures of morphine, codeine, and heroin differ? And how dothese differences alter the biological activity of these drugs?Codeine is not active in vitro (in a test tube) which means the benzene-OH of morphine is crucial for biological activity.The fact that codeine is 20% as active as morphine in vivo (in living bodies) tells us that our bodies are able to convert some codeine into morphine. The fact that 6-acetylmorphine is much more active than morphine in vivomeans it crosses the blood-brain barrier more easily than morphine. Also, it means that the other OH is not required for biological activity. The fact that heroin is more active in vivo than morphine tells us that the benzene ester can be converted into OH very easily (unlike codeine) and it crosses the blood-brain barrier easier than