Rules of the Day
4-22-2025
Click here for a copy of the lectures notes I wrote in class
Click here for a copy of the handouts I used in class today
1. High fructose corn syrup is derived from corn starch, using enzymes to convert the poly-D-Glucose polymer to individual D-glucose molecules, then converting some of the D-glucose to D-fructose in analogy to natural bee honey. It is sweeter than sucrose and far cheaper to produce.
2. The DNA and RNA nucleotides have the aromatic base linked to 2'-deoxyribose or ribose via a glycosidic bond.
3. Lipids are biological molecules that are not soluble in water such as triglycerides and steroids. Triglycerides are molecules of glycerol with three fatty acids linked by ester bonds. Steroids are 4-ring structures that provide a rigid scaffold to create distinct molecules. Steroids need to be specfic because they bind to receptors that cause many genes to be turned on or off.
4. Phospholipids make up biological membranes and are composed of two fatty acid molecules linked to glycerol along with a negatively-charged phosphate connected to a group such as positively-charged choline. Some fatty acids have Z alkenes in the middle. The Z-alkenes and even cholesterol help the membrane bilayers become fluid enough to function. Because the fatty acid chains cannot interact with water, they assemble into the bilayer structure.
You are not responsible for anything discussed below:
5. Energy drinks work by having 200-300 mgs of caffeine (resemples the AMP molecule) to turn off your drowsiness signal, combined with B vitamins that activate ATP production.
6. Many syntheses are carried out with a starting material reversibly attached to beads. This has the advantage of allowing exchange of reagents and isolation of products by simple filtration. This process can be automated! Mind officially blown! An efficient coupling strategy has been worked out for the solid phase synthesis of the phosphodiester bonds of DNA and RNA on glass beads by machine. You can order these on-line, they show up overnight by Fed-ex the next day!
7. Fentanyl is more dangerous than narcotics isolated from plants like heroin and cocaine because fentanyl is too easy to make and it is so much more potent, you do not need to transport very much material (it is too easy to hide).
8. Fentanyl binds to the mu-opioid receptor to provide a sense of euphoria (it is therefore a mu opioid agonist), but fentanyl also leads to release of A LOT of dopamine in many people, explaining why it is so addictive.
9. THERE IS NO SUCH THING AS BLACK MARKET ADDERRAL OR XANAX, THEY ARE ALL FAKE. THEY ONLY CONTAIN METHAMPHETAMINE AND FENTANYL. THESE FAKE PHARMACEUTICALS CAN KILL YOU! THEY HAVE KILLED OTHER LONGHORNS INCLUDING JAKE ELLINGER! 2 Milligrams of fentanyl will kill you. It is 150 times more potent than heroin.
10. Narcan (naloxone) is an antagonist of the mu-opioid receptor, it binds to the receptor but does not activate it or release dopamine. It binds to tightly that it can occupy all of the mu opioid binding sites and rescue a person who has OD'd on fentanyl and stopped breathing, provided it is given as a nasal spray soon enough.
11. Each of you should carry some Narcan, you can get it at the PCL circulation desk, free of charge. You just might save a life!
12. The AIDS virus is a single stranded RNA retrovirus meaning a virus particle is a single strand of RNA surrounded by virus proteins. Once inside host cells, the RNA is reverse transcribed to DNA, that then integrates into the genomes of host cells. After an unknown signal the DNA becomes active and is transcribed to long polyprotein mRNAs. A polyprotein transcript is produced from the mRNA called GAG-POL that is cleaved into functional proteins by the AIDS protease.
13. Enzymes catalyze reactions by 1) having acids, bases and nucleophiles in the active site in exactly the right places in 3-dimensions AND 2) by stabilizing transition state structures.
14. The AIDS protease is an aspartyl protease that uses two carboxylic acid groups and a water molecule to hydrolyze an amide bond at neutral pH and at room temperature.
15. Drugs are designed to interfere with the biochemical steps that are unique to the virus, in particular the reverse transcriptase (RNA to DNA) and AIDS protease steps (cleavage of GAG-POL polyprotein into individual virus proteins).
16. The AIDS protease inhibitors are designed to resemble the key tetrahedral intermediateof the amide hydrolysis reaction while maximizing complementary contacts within the active site.
17. Because the reverse transcriptase step makes a significant number of errors, the HIV genome mutates quickly and the target enzymes (reverse transcriptase and AIDS protease) can become resistant to any one drug, so "cocktails" of several drugs are used to counteract resistance.
18. I believe that developing a treatment for AIDS in about a decade stands alongside getting to the moon as one of this countries great technical achievements. The core ideas behind creating the drug are based on 1) understanding the mechanism of the enzyme reaction to be inhibited, 2) design possible drugs that bind only to the disease target, 3) synthesize then test thousands of derivatives to find the precious few that can be taken as pills and cause minimum side effects, make sure they are safe and effective, then synthesize them in large amounts in pure form, batch after batch.
You may be interested in the following publications, the ones I mentioned.
HIV drug development based on enzyme target mechanisms
Homework:
There are no quizzes, readings or homeworks for the rest of the semester! When you are ready you can work on a practice homework that will help you prepare for the final. You will not turn it in. Click here for the questions and click here for the answers.
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