Drug class - in class questions

Question 1

Name 3 toxic alkaloids

Answer 1

1. 1. Psilocin
   2. Muscarin
   3. Strychnine

Question 2

Which amino acid is a precursor for alkaloids?

Answer 2

1. 1. Valine, Phenylalanine, Tryptophan

Question 3

Voltage gated K+ and Na+ channels have similar structures. What do they look like? What are the major functional elements? Are there differences between the two?

Answer 3

1. K+ channels: 4 subunits with 6TM domains each. Each subunit is a monomer with its own inactivation segment.
2. Na+ channels: 4 subunits with 6TM domains each, are all part of the same monomer with one inactivation segment
3. Major functional elements:
   
   1. Voltage sensing helix
   2. Two helixes which change conformationally to form ion pore
   3. Inactivation segment

Question 4

1. At the neuromuscular junction, two Ca2+ channels are important to strongly increase the intracellular Ca2+ concentration in order to allow muscle contraction after a stimulus. Where are they and what Ca2+ dependent events do they mediate? Write precisely 2 sentences!

Answer 4

1. Nicotinic AchR
   
   1. Acetylcholine binding activates channel; Na+/K+
   2. Na+/Ca2+ - influx; K+ - efflux (very small)
   3. Net flow: positive charge inward
   4. Sum: resting potential -85 mV in muscle cell membrane is changed to -60 mV
   5. Opening of voltage dependent Na+ channels – voltage dependent Ca2+-channels re activated and cause Ca2+-efflux from SR
2. L-type Ca2+ channels: on plasma membrane of muscle fiber, create long lasting Ca2+ currents, interact directly with ryanodine receptors in SR. Ryanodine Receptors: Intracellular Ca2+ channels. Ca2+ induced Ca2+ release from ER or SR.

Question 5

1. Are open Cl- channels excitatory or inhibitory and why? (in other words, does their opening lead to hyperpolarization?)
2. Under which circumstances would open Cl- channels have exactly the opposite effect from what you explained above?

Answer 5

1. Are open Cl- channels excitatory or inhibitory and why? (in other words, does their opening lead to hyperpolarization?)
   
   1. Inhibitory, because resting potential is negative, so you need to let positive ions in to depolarize.
2. Under which circumstances would open Cl- channels have exactly the opposite effect from what you explained above?
   
   1. Glycine receptors are expressed in early stages of brain development
   2. Their subunit composition is developmentally regulated by developmental Cl- gradients in embryo
   3. The gradient arises through expression of chloride transporters, and thus a high intercellular chloride channel opening will lead to a depolarization in this case.

Question 6

1. Describe one signaling pathway where binding of a ligand to a receptor leads to fast changes in gene expression
2. In your answer name the ligand, the receptor and the transcription factor and consider localization of the individual components involved

Answer 6

Nuclear hormone receptors (NHRs)

Ligand: Small peptides, like hormone, steroid

Process:

1. Ligand moves through cell membrane
2. Ligand binds the NHR at the ligand binding domain (LBD)
3. NHRs dimerize (heterodimers in case of direct repeat type of NHR)
4. Translocate into nucleus
5. DNA binding domains (TXR specifically for heterodimers) bind response element on DNA
6. Transcription activation

Question 7

1. How does signal transduction work in the JAK/STAT pathway?
2. For each pathway explain in 2 sentences how transcription is activated after ligand binding to the receptors

Answer 7

1. Ligands: Cytokines:
   
   1. E.g.: Prolaktin, Interferone, Interleukin, Lymphokines, Erythropeitin
2. Process:
   
   1. Ligand binds receptor
   2. Activated receptor recruits JAK kinase
   3. 2 parts of receptor come together
   4. STAT transcription factor is recruited and phosphorylated
   5. STAT dimerizes and translocates to nucleus where it activates transcription.

Question 8

1. How does signal transduction work in the TNF pathway
2. For each pathway explain in 2 sentences how transcription is activated after ligand binding to the receptors

Answer 8

1. Ligands: TNFα
2. Pathway:
   
   1. Ligand binds receptor
   2. Receptors come together to forma trimer
   3. Conformational change leads to dissociation of inhibitory protein SODD from intracellular death domain
   4. Dissociation enables adaptor protein TRADD to bind to death domain, serving as a platform for subsequent protein binding
   5. After TRADD binding, 3 pathways can happen:
      
      1. Activation of NFκB via release from cytoplasmic complex, which is then translocated to nucleus, leading to:
         
         1. Activation of inflammatory cytokines
         2. Prostaglandin E
         3. Survival genes
      2. Activation of MAPK pathways
      3. Induction of death signaling:
         
         1. TRADD binds FADD, recruiting caspase 8
         2. Is often masked by antiapoptotic effects of NFκB

Question 9

1. How do taxol and etoposide work? Why can they be used as anti-cancer drugs?

Answer 9

1. Taxol:
   
   1. Binds to tubulin, stabilizes microtubules
   2. as a result interferes with normal breakdown of microtubules during cell division,
   3. inhibition of cell division, induces apoptosis
2. Etoposide:
   
   1. Inhibits topoisomerase II by inhibiting relegation
   2. Leads to DNA damage, apoptosis

Question 10

Which terpenes are produced in the chloroplast?

Answer 10

1. Monoterpenes and diterpenes

Question 11

1. What are tailoring enzymes? What do they do?

Answer 11

1. -alter properties of natural products (solubility, toxicity, activity or receptor-binding ability)
2. -oxidoreductases:
   
   1. –Cyt P450
   2. –Dioxygenasen
3. -Acyltransferases
4. -Glycosyltransferase
5. -Methyltransferase

Question 12

1. What are essential oils, name one

Answer 12

1. Definition: Products obtained from distillation or mechanical cold pressing of plants
2. Industrial applications: perfumes, cosmetics, detergents, pharmacology, food production
3. Usually are volatiles
4. Example: Essential oils are neurotoxic for insects
   
   1. -Thymol binds GABA receptors
   2. -Eugenol activates octopamine receptors

Question 13

1. Which class is the mammalian odor receptor?

Answer 13

1. Metabotropic GPCRs in vertebrates
2. -Ionotropic 7TM receptors in insects
3. –act as ligand gated channels