Xenobiotics

Question 1

——— is a compound that is foreign to the body.

Answer 1

Xenobiotics

Question 2

Examples of xenobiotics

Answer 2

drugs, food additives, pollutants

Question 3

Main organ involved in xenobiotic metabolism

Answer 3

Liver

Question 4

At least — different enzymes catalyze reactions involved in xenobiotic metabolism

Answer 4

30

Question 5

It is convenient to consider the metabolism of xeno- biotics in —- phases.

Answer 5

.
It is convenient to consider the metabolism of xeno- biotics in two phases.

Question 6

In phase 1, the major reaction in- volved is ———, catalyzed by members of a class of enzymes referred to as ————.

Answer 6

In phase 1, the major reaction in- volved is hydroxylation, catalyzed by members of a class of enzymes referred to as monooxygenases or cy- tochrome P450s.

Question 7

Hydroxylation may terminate the ac- tion of a drug, To F

Answer 7

F

Question 8

. In ad- dition to hydroxylation, these enzymes catalyze a wide range of reactions, including those involving

Answer 8

the ac- tion of a drug, though this is not always the case. In ad- dition to hydroxylation, these enzymes catalyze a wide range of reactions, including those involving deamina- tion, dehalogenation, desulfuration, epoxidation, per- oxygenation, and reduction.

Question 9

. Reactions involving hy- drolysis (eg, catalyzed by esterases) and certain other non-P450-catalyzed reactions also occur in phase —.

Answer 9

1

Question 10

In phase 2, the hydroxylated or other compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by ——— and list 5 things it can be done with

Answer 10

In phase 2, the hydroxylated or other compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with glu- curonic acid, sulfate, acetate, glutathione, or certain amino acids, or by methylation

Question 11

The overall purpose of the two phases of metabo- lism of xenobiotics is to ————and thus excretion from the body.

Answer 11

The overall purpose of the two phases of metabo- lism of xenobiotics is to increase their water solubility (polarity) and thus excretion from the body.

Question 12

Very hy- drophobic xenobiotics would persist in ———almost indefinitely if they were not converted to more polar forms

Answer 12

Very hy- drophobic xenobiotics would persist in adipose tissue almost indefinitely if they were not converted to more polar forms

Question 13

List 1 scenario whereby the xenobiotic is converted from an inactive to an active form
List 2 scenarios whereby the xenobiotic is converted from an active to an inactive form

Answer 13

In certain cases, phase 1 metabolic reac- tions convert xenobiotics from inactive to biologically active compounds. In these instances, the original xenobiotics are referred to as “prodrugs” or “procar- cinogens.” In other cases, additional phase 1 reactions (eg, further hydroxylation reactions) convert the active compounds to less active or inactive forms prior to con- jugation. In yet other cases, it is the conjugation reac- tions themselves that convert the active products of phase 1 reactions to less active or inactive species, which are subsequently excreted in the urine or bile. In a very few cases, conjugation may actually increase the bio- logic activity of a xenobiotic.

Question 14

In certain cases, phase 1 metabolic reac- tions convert xenobiotics from inactive to biologically active compounds. In these instances, the original xenobiotics are referred to as “——” or “——-.”

Answer 14

In certain cases, phase 1 metabolic reac- tions convert xenobiotics from inactive to biologically active compounds. In these instances, the original xenobiotics are referred to as “prodrugs” or “procar- cinogens.”

Question 15

——— is the chief reaction involved in phase 1.

Answer 15

Hydroxylation is the chief reaction involved in phase 1.

Question 16

Hydroxylation is the chief reaction involved in phase 1. The responsible enzymes are called ———— or ———-; the human genome encodes at least how many families of these enzymes. Estimates of the number of distinct cytochrome P450s in human tissues range from approximately — to —.

Answer 16

Hydroxylation is the chief reaction involved in phase 1. The responsible enzymes are called monooxygenases or cytochrome P450s; the human genome encodes at least 14 families of these enzymes. Estimates of the number of distinct cytochrome P450s in human tissues range from approximately 35 to 60.

Question 17

Full meaning of pcb

Answer 17

Polychlorinated biphenyl

Question 18

The reaction cat- alyzed by a monooxygenase (cytochrome P450) is as follows:

Answer 18

The reaction cat- alyzed by a monooxygenase (cytochrome P450) is as follows:
RH + O2 + NADPH + H+ → R — OH + H2O + NADP

Question 19

). In addition, ——— compounds, such as certain steroids, eicosanoids, fatty acids, and retinoids, are also substrates. The substrates are generally lip- ophilic and are rendered more hydrophilic by——.

Answer 19

RH above can represent a very wide variety of xenobi- otics, including drugs, carcinogens, pesticides, petro- leum products, and pollutants (such as a mixture of PCBs). In addition, endogenous compounds, such as certain steroids, eicosanoids, fatty acids, and retinoids, are also substrates. The substrates are generally lip- ophilic and are rendered more hydrophilic by hydroxy- lation.

Question 20

———-is considered the most versatile biocatalyst known.

Answer 20

Cytochrome P450 is considered the most versatile biocatalyst known.

Question 21

It has been shown by the use of molecular oxygen that one atom of oxygen enters —— and one atom en- ters ——. This dual fate of the oxygen accounts for the former naming of monooxygenases as “———.” The reaction catalyzed by cy- tochrome P450 can also be represented as follows:

Answer 21

It has been shown by the use of 18O2 that one atom of oxygen enters ROH and one atom en- ters water. This dual fate of the oxygen accounts for the former naming of monooxygenases as “mixed- function oxidases.” The reaction catalyzed by cy- tochrome P450 can also be represented as follows:
Reduced cytochrome —-> Oxidized cytochrome P450
RH+O2 →R—OH+H2O

Question 22

The major monooxygenases in the endoplasmic reticu- lum are

Answer 22

The major monooxygenases in the endoplasmic reticu- lum are cytochrome P450s

Question 23

cytochrome P450s—so named because the en- zyme was discovered when it was noted that prepara- tions of ——— that had been chemically —— and then exposed to —— exhibited a dis- tinct peak at ——nm. Among reasons that this enzyme is important is the fact that approximately —% of the drugs humans ingest are metabolized by isoforms of cy- tochrome P450; these enzymes also act on various car- cinogens and pollutants.

Answer 23

e cytochrome P450s—so named because the en- zyme was discovered when it was noted that prepara- tions of microsomes that had been chemically reduced and then exposed to carbon monoxide exhibited a dis- tinct peak at 450 nm. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cy- tochrome P450; these enzymes also act on various car- cinogens and pollutants.

Question 24

Because of the large number of isoforms (about 150) that have been discovered, it became important to have a systematic nomenclature for isoforms of P450 and for their genes. This is followed by an Arabic number designating the ——; cytochrome P450s are included in the same family if they exhibit—% or more sequence identity. The Arabic number is followed by a capital letter indi- cating the ———
, if two or more members exist; P450s are in the same subfamily if they exhibit greater than —% sequence identity. The individual P450s are then arbitrarily assigned Arabic numerals.
Thus, CYP1A1 denotes a cytochrome P450 that is a member of family — and subfamily — and is the — individual member of that subfamily. The nomenclature for the genes encoding cytochrome P450s is identical to that described above except that —— are used; thus, the gene encoding CYP1A1 is ——-.

Answer 24

P450s.
(1) Because of the large number of isoforms (about 150) that have been discovered, it became important to have a systematic nomenclature for isoforms of P450 and for their genes. This is now available and in wide use and is based on structural homology. The abbrevi- ated root symbol CYP denotes a cytochrome P450. This is followed by an Arabic number designating the family; cytochrome P450s are included in the same family if they exhibit 40% or more sequence identity. The Arabic number is followed by a capital letter indi- cating the subfamily, if two or more members exist; P450s are in the same subfamily if they exhibit greater than 55% sequence identity. The individual P450s are then arbitrarily assigned Arabic numerals. Thus, CYP1A1 denotes a cytochrome P450 that is a member of family 1 and subfamily A and is the first individual member of that subfamily. The nomenclature for the genes encoding cytochrome P450s is identical to that described above except that italics are used; thus, the gene encoding CYP1A1 is CYP1A1.

Question 25

Are cyp450 hemoproteins

Answer 25

Yes

Question 26

Cyp450, They are widely distributed across species. Bac- teria possess cytochrome P450s, and P450cam (involved in the metabolism of ——) of————is the only P450 isoform whose crystal structure has been established.

Answer 26

They are widely distributed across species. Bac- teria possess cytochrome P450s, and P450cam (involved in the metabolism of camphor) of Pseudomonas putida is the only P450 isoform whose crystal structure has been established.

Question 27

Cyp450 , They are present in highest amount in —— and —— but are probably present in all tissues. In liver and most other tissues, they are present mainly in the ————, which constitute part of the microsomal fraction when tissue is subjected to subcellular fractionation. In hepatic microsomes, cytochrome P450s can comprise as much as —% of the total protein. P450s are found in most tissues, though often in low amounts compared with liver. In the adrenal, they are found in the —— as well as in the ———; the vari- ous hydroxylases present in that organ play an impor- tant role in cholesterol and steroid biosynthesis.

Answer 27

4) They are present in highest amount in liver and small intestine but are probably present in all tissues. In liver and most other tissues, they are present mainly in the membranes of the smooth endoplasmic reticu- lum, which constitute part of the microsomal fraction when tissue is subjected to subcellular fractionation. In hepatic microsomes, cytochrome P450s can comprise as much as 20% of the total protein. P450s are found in most tissues, though often in low amounts compared with liver. In the adrenal, they are found in mitochon- dria as well as in the endoplasmic reticulum; the vari- ous hydroxylases present in that organ play an impor- tant role in cholesterol and steroid biosynthesis.

Question 28

In adrenal gland, The mitochondrial cytochrome P450 system differs from the microsomal system in that it uses an ————, ———, and a nonheme iron-sulfur protein, ——-. In addi- tion, the specific P450 isoforms involved in steroid biosynthesis are generally much more restricted in their substrate specificity.

Answer 28

. The mitochondrial cytochrome P450 system differs from the microsomal system in that it uses an NADPH- linked flavoprotein, adrenodoxin reductase, and a nonheme iron-sulfur protein, adrenodoxin. In addi- tion, the specific P450 isoforms involved in steroid biosynthesis are generally much more restricted in their substrate specificity.

Question 29

At least how many isoforms of cytochrome P450 are present in the endoplasmic reticulum of human liver, each with wide and somewhat overlapping substrate specificities and acting on both —— and —— compounds

Answer 29

At least six isoforms of cytochrome P450 are present in the endoplasmic reticulum of human liver, each with wide and somewhat overlapping substrate specificities and acting on both xenobiotics and en- dogenous compounds.

Question 30

In NADPH and NADH,which is involved in the reac- tion mechanism of cytochrome P450.

Answer 30

NADPH

Question 31

The enzyme that uses NADPH to yield the reduced cytochrome P450, is called ————. Elec- trons are transferred from —— to ——— and then to cytochrome P450. This leads to the reductive activation of ——, and one atom of oxygen is subsequently inserted into the ——-. Cytochrome —, another hemoprotein found in the membranes of the smooth endoplasmic reticulum may be involved as an electron donor in some cases.

Answer 31

The enzyme that uses NADPH to yield the reduced cytochrome P450, shown at the left-hand side of the above equation, is called NADPH-cytochrome P450 reductase. Elec- trons are transferred from NADPH to NADPH- cytochrome P450 reductase and then to cytochrome P450. This leads to the reductive activation of molec- ular oxygen, and one atom of oxygen is subsequently inserted into the substrate. Cytochrome b5, another hemoprotein found in the membranes of the smooth endoplasmic reticulum (Chapter 11), may be involved as an electron donor in some cases.

Question 32

Lipids are also components of the cytochrome P450 system. The preferred lipid is ————, which is the major lipid found in membranes of the endoplasmic reticulum.

Answer 32

.
(7) Lipids are also components of the cytochrome P450 system. The preferred lipid is phosphatidyl- choline, which is the major lipid found in membranes of the endoplasmic reticulum.

Question 33

Most isoforms of cytochrome P450 are not in- ducible. T or F

Answer 33

F they are inducible

Question 34

Most isoforms of cytochrome P450 are in- ducible. For instance, the administration of ——— or of many other drugs causes hypertrophy of the smooth endopasmic reticulum and a three- to fourfold increase in the amount of cytochrome P450 within — to —days.

Answer 34

Most isoforms of cytochrome P450 are in- ducible. For instance, the administration of phenobar- bital or of many other drugs causes hypertrophy of the smooth endopasmic reticulum and a three- to fourfold increase in the amount of cytochrome P450 within 4–5 days. The mechanism of induction has been studied ex- tensively and in most cases involves increased transcrip- tion of mRNA for cytochrome P450. However, certain cases of induction involve stabilization of mRNA, en- zyme stabilization, or other mechanisms (eg, an effect on translation).

Question 35

What happens when you take warfarin and phenobarbital together

Answer 35

Induction of cytochrome P450 has important clini- cal implications, since it is a biochemical mechanism of drug interaction. A drug interaction has occurred when the effects of one drug are altered by prior, con- current, or later administration of another. As an illus- tration, consider the situation when a patient is taking the anticoagulant warfarin to prevent blood clotting. This drug is metabolized by CYP2C9. Concomitantly, the patient is started on phenobarbital (an inducer of this P450) to treat a certain type of epilepsy, but the dose of warfarin is not changed. After 5 days or so, the level of CYP2C9 in the patient’s liver will be elevated three- to fourfold. This in turn means that warfarin will be metabolized much more quickly than before, and its dosage will have become inadequate. Therefore, the dose must be increased if warfarin is to be therapeuti- cally effective. To pursue this example further, a prob- lem could arise later on if the phenobarbital is discon- tinued but the increased dosage of warfarin stays the same. The patient will be at risk of bleeding, since the high dose of warfarin will be even more active than be- fore, because the level of CYP2C9 will decline once phenobarbital has been stopped.

Question 36

What happens when cyp2E1 is induced by the consumption of ethanol

Answer 36

Another example of enzyme induction involves CYP2E1, which is induced by consumption of ethanol. This is a matter for concern, because this P450 metabolizes certain widely used solvents and also components found in tobacco smoke, many of which are established carcinogens. Thus, if the activity of CYP2E1 is elevated by induction, this may increase the risk of carcinogenicity developing from exposure to such compounds.

Question 37

Who are the people that have higher levels of cyp1A1

Answer 37

Smokers

Question 38

CYP1A1) are particularly involved in the metabolism of ——— and related molecules; for this reason they were formerly called ———

Answer 38

CYP1A1) are particularly involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) and related molecules; for this reason they were formerly called aro- matic hydrocarbon hydroxylases (AHHs).

Question 39

Cyp1A1, in the lung it may be involved in the conversion of ———, inhaled by smoking, to——- by —— reactions.

Answer 39

. For example, in the lung it may be involved in the conversion of inac- tive PAHs (procarcinogens), inhaled by smoking, to ac- tive carcinogens by hydroxylation reactions.

Question 40

Apart from cyp1A1 being higher in smokers, it can also be found in higher levels where?

Answer 40

Some reports have in- dicated that the activity of this enzyme may be elevated (induced) in the placenta of a woman who smokes, thus potentially altering the quantities of metabolites of PAHs (some of which could be harmful) to which the fetus is exposed.

Question 41

CYP2D6, which is involved in the metabolism of —— (an antihypertensive drug) and ——- (an antiarrhythmic and oxytocic drug)

Answer 41

CYP2D6, which is involved in the metabolism of debrisoquin (an antihypertensive drug; see Table 53–2) and sparteine (an antiarrhythmic and oxytocic drug)

Question 42

One P450 exhibiting polymorphism is ——

Answer 42

One P450 exhibiting polymorphism is CYP2D6

Question 43

Another interesting poly- morphism is that of ———, which is involved in the metabolism of nicotine to conitine.

Answer 43

Another interesting poly- morphism is that of CYP2A6, which is involved in the metabolism of nicotine to conitine.

Question 44

Another interesting poly- morphism is that of CYP2A6, which is involved in the metabolism of ——— to ———.

Answer 44

Another interesting poly- morphism is that of CYP2A6, which is involved in the metabolism of nicotine to conitine.

Question 45

How many CYP2A6 al- leles have been identified: how many wild type and how many null or inactive alleles

Answer 45

Three CYP2A6 al- leles have been identified: a wild type and two null or inactive alleles

Question 46

It has been reported that individuals with the—— alleles of the cyp2A6, have impaired metabolism of nicotine, are apparently protected against becoming to- bacco-dependent smokers

Answer 46

It has been reported that individuals with the null alleles, who have impaired metabolism of nicotine, are apparently protected against becoming to- bacco-dependent smokers

Question 47

In phase 1 reactions, xenobiotics are generally con- verted to more polar, hydroxylated derivatives. In phase 2 reactions, these derivatives are conjugated with mole- cules such as —————This renders them even more —— -soluble, and they are eventually excreted in the —— or ——.

Answer 47

In phase 1 reactions, xenobiotics are generally con- verted to more polar, hydroxylated derivatives. In phase 2 reactions, these derivatives are conjugated with mole- cules such as glucuronic acid, sulfate, or glutathione. This renders them even more water-soluble, and they are eventually excreted in the urine or bile.

Question 48

List 5 types of phase 2 reaction

Answer 48

Glucuronidation
Sulphation
Conjugation with glutathione
Acetylation
Methylation

Question 49

In glucuronidation, ——— is the glucuronyl donor, and a variety of ———-, present in both the endoplasmic reticulum and cytosol, are the catalysts

Answer 49

UDP-glucuronic acid is the glucuronyl donor, and a variety of glu- curonosyltransferases, present in both the endoplasmic reticulum and cytosol, are the catalysts

Question 50

Examples of molecules that are excreted as glucuronides

Answer 50

Aniline, benzoic acid, phenol, steroids

Question 51

The glu- curonide may be attached to ——, ——, or —— groups of the substrates.

Answer 51

The glu- curonide may be attached to oxygen, nitrogen, or sulfur groups of the substrates.

Question 52

List 5 properties of cyp450

Answer 52

• Involved in phase I of the metabolism of innumerable xenobiotics, including perhaps 50% of the drugs adminis- tered to humans
• Involved in the metabolism of many endogenous com- pounds (eg, steroids)
• All are hemoproteins
• Often exhibit broad substrate specificity, thus acting on
many compounds; consequently, different P450s may cat-
alyze formation of the same product
• Extremely versatile catalysts, perhaps catalyzing about 60
types of reactions
• However, basically they catalyze reactions involving intro-
duction of one atom of oxygen into the substrate and one
into water
• Their hydroxylated products are more water-soluble than
their generally lipophilic substrates, facilitating excretion
• Liver contains highest amounts, but found in most if not
all tissues, including small intestine, brain, and lung
• Located in the smooth endoplasmic reticulum or in mito-
chondria (steroidogenic hormones)
• In some cases, their products are mutagenic or carcino-
genic
• Many have a molecular mass of about 55 kDa
• Many are inducible, resulting in one cause of drug interac-
tions
• Many are inhibited by various drugs or their metabolic
products, providing another cause of drug interactions
• Some exhibit genetic polymorphisms, which can result in
atypical drug metabolism
• Their activities may be altered in diseased tissues (eg, cir-
rhosis), affecting drug metabolism
• Genotyping the P450 profile of patients (eg, to detect
polymorphisms) may in the future permit individualization
of drug therapy

Question 53

B. SULFATION
Some alcohols, arylamines, and phenols are sulfated. The sulfate donor in these and other biologic sulfation reactions (eg, sulfation of steroids, glycosaminoglycans, glycolipids, and glycoproteins) is ————; this compound is called “———.”

Answer 53

B. SULFATION
Some alcohols, arylamines, and phenols are sulfated. The sulfate donor in these and other biologic sulfation reactions (eg, sulfation of steroids, glycosaminoglycans, glycolipids, and glycoproteins) is adenosine 3-phos- phate-5-phosphosulfate (PAPS) (Chapter 24); this compound is called “active sulfate.”

Question 54

Glutathione is a tripep- tide consisting of ———, ———, and ——.
Glutathione is commonly abbreviated
GSH (because of the ——- group of its cysteine, which is the business part of the molecule).

Answer 54

Glutathione (γ-glutamyl-cysteinylglycine) is a tripep- tide consisting of glutamic acid, cysteine, and glycine (Figure 3–3). Glutathione is commonly abbreviated
GSH (because of the sulfhydryl group of its cysteine, which is the business part of the molecule).

Question 55

Conjugation with glutathione, The enzymes catalyzing these reactions are called ————— and are present in high amounts in ——— and in lower amounts in other tissues.

Answer 55

The enzymes catalyzing these reactions are called glutathione S- transferases and are present in high amounts in liver cytosol and in lower amounts in other tissues.

Question 56

The —— and —— groups belonging to glutathione are removed by spe- cific enzymes, and an acetyl group (donated by ———) is added to the amino group of the remaining —— moiety. The resulting compound is a ———, a conjugate of L-acetylcysteine, which is then excreted in the urine.

Answer 56

The glutamyl and glycinyl groups belonging to glutathione are removed by spe- cific enzymes, and an acetyl group (donated by acetyl- CoA) is added to the amino group of the remaining cysteinyl moiety. The resulting compound is a mercap- turic acid, a conjugate of L-acetylcysteine, which is then excreted in the urine.

Question 57

Glutathione participates in the decomposition of potentially toxic hydrogen peroxide in the reaction cat- alyzed by ———

Answer 57

participates in the decomposition of potentially toxic hydrogen peroxide in the reaction cat- alyzed by glutathione peroxidase

Question 58

acetyla- tion reactions, —— (active ——) is the acetyl donor. These reactions are catalyzed by ——— present in the cytosol of various tissues, particu- larly liver.

Answer 58

acetyla- tion reactions, acetyl-CoA (active acetate) is the acetyl donor. These reactions are catalyzed by acetyltrans- ferases present in the cytosol of various tissues, particu- larly liver.

Question 59

The drug isoniazid, used in the treatment of ——-, is subject to acetylation

Answer 59

The drug isoniazid, used in the treatment of tuberculosis, is subject to acetylation

Question 60

Do Polymorphic types of acetyltransferases exist?

Answer 60

Yes

Question 61

Polymorphic types of acetyltransferases exist, resulting in individuals who are classified as —— or —— acetylators, and influ- ence the rate of clearance of drugs such as isoniazid from blood.

Answer 61

Polymorphic types of acetyltransferases exist, resulting in individuals who are classified as slow or fast acetylators, and influ- ence the rate of clearance of drugs such as isoniazid from blood.

Question 62

Methylation—A few xenobiotics are subject to methylation by ———, employing ————- as the methyl donor.

Answer 62

Methylation—A few xenobiotics are subject to methylation by methyltransferases, employing S-adeno- sylmethionine (Figure 30–17) as the methyl donor.

Question 63

THE ACTIVITIES OF XENOBIOTIC- METABOLIZING ENZYMES ARE AFFECTED

Answer 63

THE ACTIVITIES OF XENOBIOTIC- METABOLIZING ENZYMES ARE AFFECTED BY AGE, SEX,
& OTHER FACTORS

Question 64

reac- tions to drugs that reflect genetically determined differences in enzyme and protein structure among in- dividuals—part of the field of study known as ———

Answer 64

reac- tions to drugs that reflect genetically determined differences in enzyme and protein structure among in- dividuals—part of the field of study known as pharma- cogenetics (see below)

Question 65

List The toxic effects of xenobiotics under 3 headings

Answer 65

Cell injury
Altering of antigenicity
reactions of activated species of chemical car- cinogens with DNA

Question 66

the reactive species of a xenobiotic may bind to a protein, altering its antigenicity. The xenobi- otic is said to act as a ———, ie, a small molecule that by itself does not stimulate antibody synthesis but will combine with antibody once formed. The resulting an- tibodies can then damage the cell by several immuno- logic mechanisms that grossly perturb normal cellular biochemical processes.

Answer 66

Hapten

Question 67

Some chemicals (eg, benzo[α]pyrene) require activation by monooxygenases in the endoplasmic reticulum to become carcinogenic (they are thus called —— carcinogens).

Answer 67

Some chemicals (eg, benzo[α]pyrene) require activation by monooxygenases in the endoplasmic reticulum to become carcinogenic (they are thus called indirect carcinogens).

Question 68

Other chemi- cals (eg, various alkylating agents) can react directly (——carcinogens) with DNA without undergoing intra- cellular chemical activation.

Answer 68

Other chemi- cals (eg, various alkylating agents) can react directly (di- rect carcinogens) with DNA without undergoing intra- cellular chemical activation.

Question 69

The enzyme —— hydrolase is of interest be- cause it can exert a protective effect against certain car- cinogens.

Answer 69

The enzyme epoxide hydrolase is of interest be- cause it can exert a protective effect against certain car- cinogens.

Question 70

The products of the action of certain monooxygenases on some procarcinogen substrates are ———, which are are highly reactive and mutagenic or carcinogenic or both.

Answer 70

The products of the action of certain monooxygenases on some procarcinogen substrates are epoxides. Epoxides are highly reactive and mutagenic or carcinogenic or both.

Question 71

Epoxide hydrolase—like cy- tochrome P450, also present in the membranes of the endoplasmic reticulum—acts on these compounds, converting them into much less reactive ———-.

Answer 71

Epoxide hydrolase—like cy- tochrome P450, also present in the membranes of the endoplasmic reticulum—acts on these compounds, converting them into much less reactive dihydrodiols.

Question 72

———- is the study of the roles of genetic variations in the responses to drugs.

Answer 72

pharmacogenetics is the study of the roles of genetic variations in the responses to drugs.

Question 73

————has developed recently. It includes pharmaco- genetics but covers a much wider sphere of activity. In- formation from genomics, proteomics, bioinformatics, and other disciplines such as biochemistry and toxicol- ogy will be integrated to make possible the synthesis of newer and safer drugs.

Answer 73

Pharmacogenomics