Biochemistry and Pharmacology

Question 1

ligand

Answer 1

small molecule that influences receptor activity by binding directly to receptor protein at a specific site

Question 2

constitutive

Answer 2

receptor activity that occurs in the absence of agonist binding

Question 3

partial agonist

Answer 3

activate receptor, but are unable to produce the full effect of the endogenous ligand

Question 4

antagonist

Answer 4

binds to receptor and prevents the endogenous ligand from activating the receptor

Question 5

inverse agonist

Answer 5

ligands that abolish all activity

Question 6

allosteric

Answer 6

binding site other than active site

Question 7

selectivity

Answer 7

degree to which drug discriminates

Question 8

specificity

Answer 8

degree to which receptor discriminates

Question 9

activation energy

Answer 9

energy needed to overcome in order to progress in chemical reaction

Question 10

transition state

Answer 10

unstable species that is intermediate between substrate and product

Question 11

protein structure

Answer 11

tertiary structure with folds form binding sites

Question 12

effect of changing conformation

Answer 12

distort site so that ligands no longer bind efficiently

Question 13

active site

Answer 13

site at which ligand can activate the receptor to transmit a signal or inhibit the receptor to stop signal

Question 14

transmembrane receptors

Answer 14

embedded in lipid bilayer of plasma membrane
cell-surface receptor
do not need to become internalized by cell

Question 15

intracellular receptors

Answer 15

in cytoplasm or nucleus, or in membrane of extracellular compartment
must first get into cell

Question 16

extracellular receptors

Answer 16

soluble, move freely about the body

Question 17

endogenous

Answer 17

produced naturally

Question 18

exogenous

Answer 18

produced outside of the body

Question 19

Observations of receptor concept

Answer 19

1. Receptor affinity determines dose of drug needed to produce effect, and the number of receptors defines maximal effect
2. Receptors determine selectivity of a drug
3. Receptors mediate pharmacologic actions of drug as agonist or antagonist

Question 20

receptor occupancy

Answer 20

number of receptors bound to a ligand at any given time

Question 21

competitive binding

Answer 21

drug competes with endogenous ligand for binding to a receptor

Question 22

noncompetitive binding

Answer 22

ex. allosteric binding

Question 23

irreversible binding

Answer 23

appears to be noncompetitive

Question 24

association constant K

Answer 24

ratio of concentration of complex to the product of concentrations of the unbound drug and receptor

Question 25

Low K

Answer 25

more dissociation

Question 26

High K

Answer 26

more binding

Question 27

High Kd

Answer 27

more dissociation

Question 28

Low Kd

Answer 28

more binding

Question 29

Kd

Answer 29

[D][R] | [DR]

Question 30

K

Answer 30

[DR] | [D][R]

Question 31

Kd or dissociation constant

Answer 31

ease with which drug dissociates from receptor binding site

Question 32

low Kd

Answer 32

high affinity to receptor

Question 33

receptor desensitization

Answer 33

tolerance to a drug occurs as a result of a decreased receptor response

Question 34

ways that receptors become desensitized

Answer 34

internalization | reversible covalent modification

Question 35

down regulation

Answer 35

hydrolyzed within lysosome

Question 36

up-regulation

Answer 36

promotes greater sensitivity to drugs or endogenous ligands that activate a receptor signaling pathway

Question 37

four general types of receptor pathways

Answer 37

G-protein coupled receptor ion channel receptor receptor tyrosine kinase nuclear receptor

Question 38

GPCRs common mechanism

Answer 38

activate guanine nucleotide-binding proteins (G proteins)

Question 39

nucleotides are the building blocks of

Answer 39

RNA and DNA

Question 40

When GPCRs bind to agonist, stimulate G proteins to produce and bind what?

Answer 40

``` guanosine diphosphate (GDP) bind GTP ```

Question 41

Which form are G proteins active?

Answer 41

GTP-bound form

Question 42

Most G protein effectors are:

Answer 42

enzymes that produce soluble second messenger that carries on the signal initatied by GPCRs

Question 43

Some GPCRs are negatively coupled to adenylyl cyclase

Answer 43

activation of receptor turns on an inhibitory G protein that blocks adenylyl cyclase and decreases cAMP formation

Question 44

positively coupled

Answer 44

turn on stimulatory G protein and produce more cAMP

Question 45

ion channels

Answer 45

transmembrane, gated so conformational changes in receptor protein can open or close channel

Question 46

ligand vs. voltage

Answer 46

respond to binding of endogenous ligand vs. changes in membrane potential

Question 47

refractory period

Answer 47

time for resting potential of membrane to be restored, cannot be stimulated to open

Question 48

Receptor Tyrosine Kinases

Answer 48

transmembrane, regulatory receptors as well as enzymes

Question 49

kinase

Answer 49

enzyme facilitates transfer of single phospate from ATP to tyrosine amino acid residue

Question 50

autophosphorylation

Answer 50

RTKs attach phosphates to themselves

Question 51

nuclear receptors

Answer 51

intracellular receptors

Question 52

ex. of nuclear receptors

Answer 52

steroid receptors

Question 53

therapeutically important effects of nuclear receptor drugs and hormones

Answer 53

Produce effects only after lag period | Effects may continue for days

Question 54

Drug classes that interact with Adrenergic Receptor

Answer 54

``` Autonomic Alpha adrenergic agonists Alpha adrenergic antagonists Beta adrenergic agonists Beta adrenergic antagonists ```

Question 55

Drug classes that interact with Cholinergic Receptor

Answer 55

Autonomic drugs Cholinergic agonists Cholinergic antagonists Neuromuscular blockers

Question 56

Drug classes that interact with Dopaminergic

Answer 56

Dopamine agonists | Dopamine antagonist

Question 57

Drug classes that interact with Serotonergic

Answer 57

Serotonin agonists | Serotonin antagonists

Question 58

Drug classes that interact with Histaminic

Answer 58

Antihistamines

Question 59

Drug classes that interact with Opioid

Answer 59

Opioid agonists and antagonists

Question 60

Michaelis constant Km

Answer 60

concentration of substrate necessary to achieve half of maximal velocity

Question 61

two main types of cofactors that participate in enzymatic reactions:

Answer 61

Coenzymes | Prosthetic groups

Question 62

coenzymes

Answer 62

held loosely by enzyme and may be released easily

Question 63

prosthetic groups

Answer 63

tightly (covalently bound) cofactors

Question 64

Drug enzyme interactions

Answer 64

``` competitive (drug blocks substrate access) non competitive (lower activation energy by binding to allosteric site) ```

Question 65

competitive inhibitors shift plot of reaction velocity

Answer 65

increase Km; Vmax same

Question 66

noncompetitive and irreversible effect on Vmax

Answer 66

change apparent Vmax; not affect Km

Question 67

six major classes of enzymes

Answer 67

``` oxidoreductases transfereases hydrolases lyases isomerases ligases ```

Question 68

oxidoreductase

Answer 68

oxidize substrates by transferring an electron to an electron accepting cofactor

Question 69

example of oxidoreductase

Answer 69

ALDH - chemical oxidation of acetaldehyde to acetic acid after consuming alcohol

Question 70

transferases

Answer 70

transfer of phosphate group from ATP to amino acid residue by kinases

Question 71

hydrolases

Answer 71

split larger molecules into smaller ones, using a molecule of H2O