Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Med Chem Final > Lecture 1 > Flashcards

Lecture 1 Flashcards

You may prefer our related Brainscape-certified flashcards:
AP® Chemistry flashcards Periodic Table flashcards Chemistry 101 flashcards Organic Chemistry 101 flashcards
1
Q

Metabolism plays an important role in….

A

the elimination of drugs and other foreign substances from the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the term for “foreign substances” that are removed through the process of metabolism?

A

xenobiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

xenobiotics are relatively ___ soluble

A

lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

metabolic reactions covert the relatively lipid soluble xenobiotics to….

A

water soluble (hydrophilic) compounds that can be excreted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what would happen if lipophilic drugs were not metabolized to more polar, water soluble products?

A

they would remain in the body indefinitely eliciting their biological effects (bc they would not be readily excretable, water soluble products)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

do water soluble drugs need to be metabolized?

A

no. they are simply filtered and eliminated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

metabolism leads to compounds that are…..

A

generally pharmacologically LESS ACTIVE and relatively nontoxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

as mentioned, metabolism leads to compounds that are generally pharmacologically LESS ACTIVE and relatively nontoxic.

therefore, drug metabolism reactions are also regarded as ____ processes

A

detoxification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

sometimes, the metabolite can be…..
(3 things)

A

-toxic
-biologically active
-activate an inactive drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

as mentioned, sometimes the metabolite that results from a metabolic reaction can be toxic.

give a specific example of this

A

acetaminophen is metabolized to N-acetylimidoquinone which is a TOXIC METABOLITE and can cause liver toxicity if too much acetaminophen is taken

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

as mentioned, sometimes the metabolite that results from a metabolic reaction can be biologically active

give a specific example of this and explain the significance

A

when diazepam undergoes metabolism, it is converted to an ACTIVE METABOLITE - Oxazepam.

THERFORE, the presence of the parent molecule (diazepam) cannot be used to signal the end of the duration of action, because the metabolite is also active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

true or false

it is typical of benzodiazepines to have a metabolite that is biologically active

A

true.

such is the case for diazepam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

as mentioned, sometimes the metabolite from the metabolism of a drug can activate an inactive drug

give a specific example of this

A

such is the case with prodrugs

protonsil gets bioreduced to produce the active antibiotic – sulfonamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

true or false

drug metabolism is a straightforward detoxification

A

FALSE.

there are 3 exceptions as mentioned. the metabolite can be toxic, be biologically active, or activate an inactive drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

name the 2 categories of metabolic reactions

A

phase 1 (functionalization reactions)

phase 2 (conjugation reactions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

true or false

benzene is lipophilic

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the function of phase 1 of drug metabolism

A

to “functionalize” the starting material that has no functional group

for example, if starting with benzene a hydroxyl group can be added to form phenol. this molecule can then undergo conjugation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

if you are starting with a drug molecule that has a phenol functional group, is phase 1 of drug metabolism needed?

A

usually not, but it depends

in theory, if a molecule already has a “built in” polar functional group, phase 1 shouldn’t be needed.

however, if too much of the drug is ingested, phase 1 might still be needed. this is the case for acetaminophen. It has a built in polar functional group so phase 1 is usually bypassed, but if too much is taken, acetaminophen might undergo phase 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

true or false

diazepam’s metabolite is toxic

A

FALSE – it is biologically active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

the main purpose of functionalization (phase 1) reactions is to _______ into _______

A

introduce a polar functional group into a xenobiotic (foreign) molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

as mentioned, the main purpose of functionalization reactions is to introduce a polar functional group into a xenobiotic molecule.

name the most common of these functional groups

A

-OH (hydroxyl)
-COOH (carboxyl)
-NH2 (amine)
-SH (thiol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

the main organ that handles drug metabolism

A

the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

as mentioned, the main purpose of the phase 1 reactions of drug metabolism is to introduce a polar functional group into a xenobiotic molecule

explain how this is accomplishes

A

mainly through the liver microsomal enzymes through 3 reactions:

-oxidations
-reductions
-hydrolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Phase 1 reactions provide a _____ in the form of _____ to undergo_____

A

phase 1 reactions provide a HANDLE in the form of POLAR FUNCTIONAL GROUPS (-OH, -COOH, -NH2, -SH) to undergo PHASE 2 REACTIONS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Phase 2 reactions are also known as ____ reactions

A

conjugation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Phase 2 (conjugation) reactions attach ______ to _________

A

phaase 2 reactions attach POLAR AND IONIZABLE GROUPS to:

-the phase 1 metabolites OR

-the xenobiotics already containing the necessary polar functional groups

to form water soluble CONUJUGATED PRODUCTS devoid of activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

name 3 typical phase 2 reactions

A

-glucuronic acid conjugation
-sulfate conjugation
-glycine, glutamine, and other amino acid conjugation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

glucuronic acid conjugation can also be called…

A

glucuronidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

sulfate conjugation can also be called…

A

sulfation - attaching sulfate group to substrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what are the typical amino acids that undergo phase 2 metabolic reactions?
can other amino acids participate in phase 2 reactions?

A

typical: glycine and glutamine

the conjugation of other amino acids is possible, but it depends on the species involved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

explain the metabolites that result from the 3 most common conjugation reactions (listed above)

A

they are GENERALLY pharmacologically inactive,
VERY POLAR and are readily excreted in the urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

besides:

-glucuronic acid conjugation
-sulfate conjugation
-glycine, glutamine, and other amino acid conjugation

name 3 other phase 2 reactions

A

glutathione conjugation
acetylation
methylation

33
Q

what is GSH

A

glutathione

34
Q

explain the main purpose of glutathione conjugation

give a specific example of how it accomplishes this purpose

A

to protect the body against chemically reactive metabolites/xenobiotics

for example, the metabolite of acetaminophen (N-Acetylimidoquinone) is chemically reactive and can cause liver toxicity.

glutathione intercepts this chemically reactive metabolite. Several steps occur and acylated cysteine is added to the molecule. Also, the carbonyl gets reduced to an alcohol (OH). – forms MERCAPTURIC ACID

this molecule is now STABLE

35
Q

what are 2 brand names of acetaminophen?

A

tylenol, tempra

36
Q

name for a benzene ring with a carbonyl at the 1 and 4 positions

A

1,4-benzoquinone

37
Q

what is the name of the metabolite of acetaminophen? how is it formed?

A

N-Acetylimidoquinone

produced under several steps via oxidation

38
Q

in GSH conjugation, how are the metabolites excreted?

A

GSH derivatives are not excreted this way. they undergo further biotransformation to form MERCAPTURIC ACID DERIVATIVES which THEN are excreted

39
Q

what are the 2 phase 2 reactions whose primary goal is to terminate biological activity?

A

acetylation and methylation

40
Q

what 3 phase 2 reactions are different from typical conjugation reactions?
explain how they’re different

A

GSH conjugation, acetylation, and methylation

do not significantly increase water solubility or produce water soluble metabolites

41
Q

for which 3 conjugation reactions is the primary goal to terminate biological activity?

A

GSH conjugation, acetylation, and methylation

42
Q

there are 3 “typical” conjugation pathways and 3 “nontypical” conjugation pathways.
name them

A

typical – produce biologically inactive, water soluble molecules:
-glucuronic acid conjugation
-sulfate conjugation
-glycine, glutamine, and other amino acid conjugation

nontypical - DONT ENHANCE WATER SOLUBILITY - just terminate biological activity
-GSH conjugation
-methylation
-acetylation

43
Q

do any of the 3 “nontypical” conjugation reactions ever DO produce polar/water soluble metabolites?

A

yes.

methylation can lead to a water soluble metabolite when a QUATERNARY AMMONIUM DERIVATIVE IS FORMED (very rare)

44
Q

explain the structure of quaternary ammonium

A

Nitrogen with 4 substituents attached and thus has a + charge

45
Q

____ is a tripeptide

A

GSH (glutathione)

46
Q

what does MFOS stand for

A

mixed function (mono)oxidase system

47
Q

what does the MFO system require?

A
  1. An oxygenating agent
  2. a reducing cofactor
48
Q

the MFO system requires:

-an oxygenating agent
-a reducing cofactor

typically, what is used to serve these 2 functions?

A

molecular oxygen is typically used as an oxygenating agent, all depending on the presence of oxygen molecules.

the reducing cofactor is typically NADPH

49
Q

what are the enzymes involved in MFOS?

A

-cytochrome p450
-NADPH-cytochrome P-450 reductase
-NADH-cytochrome b5 reductase

50
Q

the mixed function oxidase system is part of phase ___ of drug metabolism

A

ONE

51
Q

explain what MFO does

A

inserts only ONE ATOM of oxygen into the substrate (drug) and the other oxygen atom ends up in H2O.
MFO activates molecular oxygen which, in turn, OXIDIZES the substrate

52
Q

true or false

dioxygenase enzymes are used in the MFO system

A

FALSE - only involves the transfer of 1 atom of oxygen.

involves mono oxygenases (cytochrome P450)

53
Q

explain the structure of Cytochrome P-450

A

it contains:

heme portion - made of iron containing porphyrin. IDENTICAL throughout all the Cytochrome P-450 isozymes. it actually delivers the oxygen atom to the substrate.

protein portion - apoprotein.
serves as the drug binding site and provides SELECTIVITY for different isozymes of cytochrome p450

54
Q

what is the main catalytic place of MFOS?

A

the heme portion of cytochrome P450

55
Q

what is the drug binding site of MFO system?

A

the protein portion of cytochrome P450

56
Q

why is Cyt P-450 given that name?

A

when the heme portion of the enzyme containing ferric (Fe+3) is reduced to ferrous (Fe2+) and reacts with carbon monoxide (typically in a lab setting) the enzyme gives a characteristic absorption at 450nm

57
Q

true or false

the MFO system does not express much versatility

A

FALSE –

xenobiotics with diverse structures can be metabolized by the MFO system by a VARIETY of oxidative reactions

with base substrate as RH, R can be alkyl, aryl, etc
also not limited to just C-H bonds

58
Q

how is the MFO system able to have such versatility?

A

it has broad substrate specificity and also has multiple isozymes (isoforms) of cytochrome p450

59
Q

where is the MFO system found in high concentrations?

A

in the liver

60
Q

besides the liver, where else is the MFO system found?

A

lungs, kidney, adrenal cortex, skin, placenta, intestine

61
Q

where SPECIFICALLY is the MFO system found? (not an organ)

A

it is a MEMBRANE BOUND ENZYME and is in the endoplasmic reticulum

62
Q

MFO system is a membrane bound enzyme in the endoplasmic reticulum.

what kind of environment is this? (lipophilic or hydrophilic)
WHY?

A

LIPOPHILIC

lipophilic substrates are taken in to be metabolized by MFO

63
Q

what is the S9 fraction?

A

contains CYt P-450 enzymes.
used to represent in vitro phase 1 reaction in the lab setting

64
Q

give the general chemical reaction for the MFO system

A

R-H + NADPH + O2 +H+ —> R-OH + NADP+ + H2O

65
Q

which portion of Cytochrome P-450 has interaction with the activated oxygen species?

A

the heme portion (catalytic portion)

they’re in very close proximity.
the drug is bound to the substrate binding site (apoprotein portion of cytp450) and the reactive O is inserted between the R and H to form ROH

66
Q

what is another name for the heme portion of cytochrome p450

A

protoporphyrin IX

67
Q

STEP 1: cytochrome p450 forms a complex with what? what kind of complex is it?

A

the ferric (+3) ion in the heme portion of cytochrome p450

BINARY COMPLEX. contains 2 components - ferric and substrate

68
Q

STEP 2: after the drug (substrate) forms a binary complex with ferric, what happens?

A

the coenzyme (NADPH) participates by donating an electron via the Cytochrome p450 reductase enzyme.

this reduces ferric (+3) to ferrous (+2)

this is ALWAYS the first electron donation step (the second step has 2 potential options)

69
Q

STEP 3:
what happens after NADPH has donated an electron to reduce ferric to ferrous?

A

ferrous interacts with molecular oxygen (O2) to form a TERTIARY COMPLEX:
-O2
-P450 with ferrous
-substrate

before this step occurs is when the binary complex (ferrous (fe2+)) can react with carbon monoxide in the lab produce a complex with CO. complex is now p450 with ferrous + substrate+ CO
this chromophore (molecule that absorbs light at a particular wavelength) absorbs characteristically at 450nm.

70
Q

After the binary complex reacts with molecular oxygen to form a tertiary complex, what happens next?

A

another electron is provided from 1 of 2 sources:

-from NADPH through cytochrome p450 reductase OR
-From NADH through cytochrome b5 reductase

this produces an ACTIVATED tertiary complex and ferrous is oxidized back to ferric

71
Q

what happens after the second electron is added?

A

2 electrons are provided - 1 from NADPH and 1 from the oxidation of ferrous back to ferric.

this pair of electrons, with 1 atom from the bound molecular oxygen, forms a WATER MOLECULE

this produces an ACTIVATED OXYGEN SPECIES:
p-450 connected to ferric, O, RH at the substrate binding site

this activated oxygen species then oxidizes the product and it is released, forming R-OH

72
Q

how are the cytochrome p450s named?

A

CYP-number-capital letter-number

73
Q

the cytochrome p450sare named with
CYP-number-capital letter-number

explain this further

A

1st number = family

Capital letter = subfamily

next # = individual enzyme in a subfamily

74
Q

how are the families and subfamilies of the cytochrome p450 enzymes determined?

A

by amino acid sequence homology

75
Q

what is one of the most common cytochrome p450 enzymes that handles most drugs?

A

CYP3A4

76
Q

Approximately how many of the P-450 gene families are identified in mammals?

A

~14 families

77
Q

for liver metabolism (in humans), there are ______ main cytochrome p450 families:

A

3 main families:
CYP1, 2, and 3

78
Q
A

Med Chem Final (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions