Medicinal Chemistry Ii Exam 2

Front 1

What is the predominant form of Vit A obtained from plant sources?
How is it absorbed from the intestine into the enterocyte?
In the enterocyte, this precursor to Vit A can be oxidized to retinal?
To what enzyme does retinal bind while it is further processed, what is the intermediate that is formed in the process and what is the final product of the process?

Back 1

B-carotene
Incorporated into mixed micelles and absorbed at SRB-1
B-carotene
CRBP II
Retinol or Rol
Retinol ester or Re

Front 2

In what form of Vitamin A from animal sources presented to target organs from blood?
To what enzyme does that form of Vitamin A bind in target organs, what is the first enzyme that further processes it and what is finally formed in the target organ?

Back 2

Retinol or Rol
CRBP I
Retinol dehydrogenase or RDH
Retinoic acid or RA
or
Retinol ester or Re
Retinol ester hydrolase or ReH
RDH
RA

Front 3

Retinoic acid in the nucleus binds to what receptor?
Which forms a heterodimer with what other receptor?
The heterodimer binds to what part of DNA?

Back 3

RAR
RXR
RARE (Retinoic acid response element)

Front 4

Distinguish between the following oxides of nitrogen.
N2O
NO
NO2

Back 4

N2O
Nitrous oxide
Laughing gas
Weak GA (general anesthetic)

NO
Nitric oxide
Made in body

NO2
Nitrogen dioxide
Red-brown and/or toxic

Front 5

Identify where the concentrations of the ion is greater (extracellular vs. intracellular) and if the corresponding ion channels are blocked or opened by antiepilepsy drugs.
Na+
Pick One:
Extracellular/Intracellular
Blocked by AEDs/Opened by AEDs

Back 5

Extracellular
Blocked by AEDs

Front 6

Identify where the concentrations of the ion is greater (extracellular vs. intracellular) and if the corresponding ion channels are blocked or opened by antiepilepsy drugs.
K+
Pick One:
Extracellular/Intracellular
Blocked by AEDs/Opened by AEDs

Back 6

Intracellular
Opened by AEDs

Front 7

Identify where the concentrations of the ion is greater (extracellular vs. intracellular) and if the corresponding ion channels are blocked or opened by antiepilepsy drugs.
Ca2+
Pick One:
Extracellular/Intracellular
Blocked by AEDs/Opened by AEDs

Back 7

Extracellular
Blocked by AEDs

Front 8

Identify where the concentrations of the ion is greater (extracellular vs. intracellular) and if the corresponding ion channels are blocked or opened by antiepilepsy drugs.
Cl-
Pick One:
Extracellular/Intracellular
Blocked by AEDs/Opened by AEDs

Back 8

Extracellular
Opened by AEDs

Front 9

Name 4 receptors associated with ligand-gated ion channels that are targeted by AEDs, the ions regulated by them and the major neurotransmitters that act on them as ligands.

Back 9

GABA-A: Chloride ion, GABA
NMDA: Calcium ion, Glutamate
KA: Sodium ion, Glutamate
AMPA: Sodium, Glutamate

Front 10

Which of the following actions is NOT expected to lead to antiepileptic effects?
a. Inhibit glutamic acid decarboxylase
b. Inhibit GABA-transaminase
c. Block NMDA receptor
d. Block GABA-A receptor
e. Prevent glutamate release by presynaptic neurons
f. Prevent GABA re-uptake by presynaptic neurons

Back 10

a. Inhibit glutamic acid decarboxylase
d. Block GABA-A receptor

Front 11

What is the predominant form of Vit A found in meals composed of diary products? The predominant form of vitamin A in dairy products can be metabolized to another form of Vit A. Name it and identify an enzyme responsible for its formation. Explain how each form is absorbed into the enterocyte and identify differences in the two absorption processes. What is (are) the form(s) of Vit A from diary products that is (are) incorporated into chylomicrons.

Back 11

Retinol ester or Re
Retinol (Rol) by retinol ester hydrolase (ReH)
Retinol (Rol) absorbed passively
Retinol ester (Re) solubilized by mixed micelles and absorbed SRB-I
Retinol ester (Re) and retinol (Rol)

Front 12

(CH3)2-CH-CH2-CH2-CH2-ONO2
To what chemical class does the following molecule belong to? Write the chemical species it produces on chemical hydrolysis. Show how the product of the enzymatic hydrolysis is converted to the active species. Why does the product of the chemical hydrolysis inhibit formation of the active species?

Back 12

a. Nitrate ester
b. NO3 (-)
c. NO2 (-)
d. 3 x NO2 (-) + 3H (+) <--> 3 HNO2 <--> 2 x NO + H2O + NO3 (-) <--> HNO3
e. Mass action: More NO3 (-) in above equation causes equilibrium to go backward

Front 13

Describe one way cholesterol can be absorbed into the enterocyte. Describe one way in which cholesterol esters can be absorbed into the enterocyte. Describe one way in which bile acids are absorbed into the enterocyte. Name a class of drugs that inhibits the later process.

Back 13

1. iCT Intestinal cholesterol transporter
2. Mixed micelles formed that deliver to SR-B1
3. Mostly iBAT intestinal bile acid transporter
4. Bile acid sequestering agents - choletyramine

Front 14

Name 2 mechanisms of local anesthetics discussed in class.

Back 14

Prevent the generation and conduction of the nerve impulse
Primary site of action if the cell membrane
Block conductance by decreasing or preventing the transient increase in the permeability of excitable membranes to Na+
Local anesthetics have a direct action with voltage gated Na+ channels
Can bind to other membrane proteins
Can block K+ channels (requires a higher drug concentration)

Front 15

Which are the two different forms of Vit A and one precursor to Vit A that can be incorporated into chylomicron? Inside of the liver one of the forms of Vit A (found in animal sources) is converted by an enzyme to the other form of Vit A. Name which form is converted to the other form and name the enzyme that causes the conversion.

Back 15

1. Rol and Re; B-C
2. Re; ReH

Front 16

All trans retinol is transported to the eye from the liver by a complex of two carrier proteins. Name the carrier proteins. How does all trans-retinol get inside the eye? Name the enzyme and binding protein responsible for converted all trans-retinol to its palmitate ester in the eye.

Back 16

1. RBP and TTR
2. *Passive diffusion* after release from complex
3.CRBP-I, LRAT

Front 17

How is all trans-retinoic acid transported into the nucleus? To what receptor does it bind in the nucleus and to what other receptor does that all-trans retinoic acid monomer bind to form a dimer?

Back 17

Bound to CRABP-I
RAR
RXR

Front 18

After 11-cis retinol is formed in the eye, to what is it converted and which enzymes/binding proteins are involved? Which carrier protein transports the corresponding product to the rod part of the eye and what is the name of the first chemical reaction that takes place in the eye?

Back 18

11-cis Retinol (Rol) --CRALBP and 11-RDH--> 11-cis Retinal (Ral)

IRBP is carrier protein
Formation of an imine or protonated imine

Front 19

Describe two pathways in which triglycerides can be absorbed into the enterocytes. One pathwayway contains 4 different processes and 2 intermediates. Make sure to name them all. What role does a bile acid play in one of the pathways?

Back 19

1. Solubilized into micelle, aided by bile acid
2. Hydrolysis of Tg into:
3. Monoglycerides and fatty acids
4. Passive absorption
5. Reconstituted into Tg

1. Solubilization or mixed micelle
2. Absorbed inact via SRB-I

Front 20

(CH3)2-CH-CH2-CH2-NO2

To which chemical class does the following drug belong? What is the structure of the product of its chemical hydrolysis? What is the structure of the product of its enzymatic hydrolysis and what is the name of the enzyme involved in the hydrolysis/reduction? What is the name of the functional groups in the enzyme that are involved in the hydrolysis/reduction. What are the products of the acid disproportionation of the product of the ezymatic hydrolysis?

Back 20

Nitrate ester
Chemical NO3 (-)
Enzymatic NO2 (-)
GONR
RSH Sulfhydride thiolate
NO3 (-) + NO

Front 21

Although lipid solubility is a desired feature of inhalation anesthetics, too much lipid solubility can have adverse effects. Describe these in one or two sentences.

Back 21

1. Long recovery times as anesthetic comes out of CNS slowly
2. Possible toxic metabolism as a result of long residence time in the liver.

Front 22

Nitrous oxide, although not a potent inhalation anesthetic, is often administered prior to or concomitant with the administration of potent fixed anesthetics. Why?

Back 22

To minimize the required amount of the more potent (and toxic fixed anesthetic)

Front 23

Propofol (dipravan) is only about 30% conjugated with glucuronic acid during its metabolism and prior to excretion. The remaining 70% is excreted unchanged. Why is the metabolic esterification reaction so inefficient?

Back 23

The two isopropyl groups, ortho to the phenolic OH which would be conjugated, sterically block access of glucuronic acid to the OH.

Front 24

Why is ketamine used animals and human children but not in human adults as an injectable anesthetic.

Back 24

In adults it causes hallucinations.

Front 25

Low water solubility and high lipid solubility are associated with what desirable properties of general anesthetics?

Back 25

Fast onset and fast recovery from anesthesia

Front 26

How does Vit A get to target organs from storage in the liver. Make sure to identify any binding protein used in the process.

Back 26

Stored Re (retinol ester) --ReH--> Rol (retinol)
Rol bound to RBP * TTR --Blood--> Rol released and passively absorbed at target organs

Front 27

What are the three chemical reactions that take place with 11-cis retinal in the rod part of the eye to generate all-trans retinol besides the effect of light?

Back 27

11-cis retinal (RCH=O) + opsin-NH2 ---> opsin-N=CHR 11-cis imine formation --hv light--> opsin N=CHR all trans --hydrolysis-->all trans-RCH=O retinol --RDH reduction--> All trans retinol

Front 28

What is the predominant form of Vit A (provitamin) that is absorbed from a meal composed of broccoli and pumpkins. Explain how the provitamin is processed in the enterocyte to give two molecules that can be incorporated into chylomicrons. Name two molecules and the enzymes (4 of them) and intermediate in the process.

Back 28

B-carotene is the predominant form
B-carotene --deoxygenase--> Ral --reduction--> Rol --LRAT--> Re
CRBP-II

Front 29

How is all-trans retionic acid formed in target organs from all-trans retinol. Name the enzyme to retinol is bound, the enzyme that acts on it and the intermediate. To what does all trans retinoic acid bind that transports it into the cell and to what does it bind in the nucleus to cause transcription.

Back 29

Rol --CRBP-I and RDH--> Ral
RA binds to CRABP-I for transport
RA binds to RAR (or RARE) to cause transcription

Front 30

In the eye all trans-retinol is converted to 11-cis retinal. Explain all the steps in the process including any enzymes and binding proteins that are necessary as well as any intermediates.

Back 30

Trans-Rol --CRBP and LRAT--> Trans Re --ISOM--> 11-cis Rol --CRALBP and 11-RDH--> 11-cis Ral

Front 31

What is the predominant form of Vit A found in meals composed of dairy products? How is this form of Vit A absorbed intact? What other form of Vit A is produced during absorption of Vit A from dairy products?

Back 31

Retinol ester
Solubilized by bile acids, form micelles which are absorbed at SRB1
Retinol (Rol) formed from Re by hydrolysis

Front 32

What is the form of Vit A that is obtained from plant sources and how is it absorbed? How does it get to target organs?

Back 32

B-carotene (B-C) solubilized by bile acids form micelles that absorb at SR-B1
B-C packaged into chylomicrons. Chylomicrons (Cm) coated with ApoE direct Cm (or CmR) to LDLR on target cells.
or
ApoB48 directs CmR to CMRR on liver cells

Front 33

How does retinol get to target organs from storage in the liver? Make sure to identify any binding proteins used in the process.

Back 33

Retinol ester (Re) hydrolyzed by ReH. Retinol (Rol) binds to RBP. TTR in liver then secreted into blood stream and absorbed at target organ passively.

Front 34

What is that form of Vit A which is responsible for differentiation of target cells in organs? How is it synthesized from the predominant storage form of Vit A in the target cells and how does it get to its receptor? Make sure to identify any binding proteins used in the process.

Back 34

Retinoic acid (RA)
Retinol ester (Re) hydrolyzed by ReH to retinol (Rol)
Rol binds to CRBP-I and is oxidized by retinol dehydrogenase and by retinal dehydrogenase to RA which binds to CRABP-I for transport to nucleus

Front 35

What are the chemical and biochemical reactions that take place with 11-cis retinal in the rod part of the eye?

Back 35

11-cis retinal reacts with opsin-NH3 or NH2 --> (imine) cis-CH=N-opsin --hv light-->trans-CH=N-opsin --hydrolysis--> trans-CH=O --RDH--> trans-CH2-OH

Front 36

How many international units in 1 microgram of all-trans retinol?

Back 36

1 iu = 0.3 mg all trans retinol
1 mg = 1000 micrograms
(1000 micrograms)(1 iu) / (0.3 micrograms) = 3,333 iu