RNA: Metabolism Of Xenobiotics

Question 0

Is a compound that is foreign to the body. It may include drugs, chemical carcinogens, and various other compounds. May be excreted unchanged, or it may be metabolized by the body’s enzymes to other compounds.

Answer 0

Xenobiotics

Question 1

Metabolism of Xenobiotics occur mostly in the

Answer 1

Liver

Question 2

Xenobiotics may convert __________ into cytotoxic, muthagenic compounds.

Answer 2

Procarcinogenics

Question 3

Metabolism of one xenobiotic may influence metabolism of another __________. Examples: drugs & other foreign non-essential compounds.

Answer 3

Xenobiotics

Question 4

Xenobiotic metabolized before reaching general circulation

Answer 4

First-pass metabolism

Question 5

Pathway of Xenobiotics Metabolism: Attachment of new functional groups, transformation of exist functional gro oxidation, reduction, hydroxylation, hydrolysis & etc.

Answer 5

Phase 1 Biotransformation/Hydroxylation

Question 6

Pathway of Xenobiotics Metabolism: Masking of an existing functional group by acetylation, glycosylation, attachment of an AA, or other mechanism.

Answer 6

Phase 2 Conjugation

Question 7

2 Phases of Xenobiotic Metabolism

Answer 7

Hydroxylation/Biotransformation and Conjugation

Question 8

Catalyzed by cytochrome P450, a monooxygenase. May sometimes terminate the action of a drug. Other phase 1 reactions may include deamination, dehalogenation, desulfuration, epoxidation, peroxygenation and reduction. Reactions involving ________ also occur in phase 1.

Answer 8

Hydroxylation. Hydrolysis.

Question 9

The reaction catalyzed by a _________ is as follows: RH + 02 + NADPH + R- OH + H2O + NADP. It is sometimes referred to as a Mixed Function Oxidase. Approximately 50% of the drugs humans ingest are metabolized by isoforms of __________.

Answer 9

Monooxygenase. Cytochrome P450.

Question 10

Compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with glucuronic acid, sulfate, acetate, glutathione, or certain AA or by methylation.

Answer 10

Conjugation

Question 11

The most frequent conjugation reaction

Answer 11

Glucuronidation

Question 12

Is the glucuronyl donor

Answer 12

UDP-glucuronic acid

Question 13

Are the catalyst in Glucuronication

Answer 13

Glucuronosyltransferases

Question 14

Sulfate donor is ____________ called “active sulfate.”

Answer 14

Sulfation. Adenosine-3-phosphate-5-phosphosulfate PAPS.

Question 15

Is a tripeptide consisting of glutamic acid, cysteine, and glycine.

Answer 15

Glutathione

Question 16

Are conjugated to the nucleophilic GSH: R+GSH—>R-S-G. The enzymes catalyzing these reactions are called ____________ and are present in high amounts in liver _______.

Answer 16

Electrophilic xenobiotics(carcinogens). Glutathione S-transferases. Cytosol.

Question 17

Catalyzed by acetyltransferases present in the cytosol of various tissues, particularly the _________. X+Acetyl-CoA-X+CoA.

Answer 17

Acetylation. Liver.

Question 18

Used in the treatment of tuberculosis, is subject to acetylation.

Answer 18

Isoniazid

Question 19

In Acetylation, Polymorphic types of __________ exist, resulting in individuals who are classified as slow or fast acetylators.

Answer 19

Acetyltransferases

Question 20

Are more subject to certain toxic effects of isoniazid because the drug persists longer in these individuals.

Answer 20

Slow Acetylators

Question 21

Has several soluble UDP-Gluc-transferases

Answer 21

Liver

Question 22

Is found in many tissues including liver

Answer 22

NAT enzymes

Question 23

Purpose of Xenobiotics: to increase the _________ of the xenobiotic and facilitate _______ from the body.

Answer 23

Water solubility. Excretion.

Question 24

Purpose of Xenobiotics: If xenobiotic is not metabolized, it would remain in the ___________ and would be stored indefinitely in the _________.

Answer 24

Nonpolar state. Adipose tissue.

Question 25

Fate of Xenobiotic Metabolism: It may be converted from an _______ to a biologically ______ compound (prodrug or ________)

Answer 25

Inactive. Active. Procarcinogen.

Question 26

Fate of Xenobiotic Metabolism: Additional phase 1 reactions may convert the active compounds to _______ or _______ forms prior to conjugation.

Answer 26

Less active. Inactive.

Question 27

Fate of Xenobiotic Metabolism: In other cases, it is the ________ reactions that convert the active products of phase 1 reactions to less active or inactive species, which are subsequently excreted in the urine or bile.

Answer 27

Conjugation

Question 28

Fate of Xenobiotic Metabolism: In few cases, conjugation may increase the biologic activity of a

Answer 28

Xenobiotic

Question 29

Properties of Human Cytochrome P450: All are _________. Exhibit ______ substrate specificity.

Answer 29

Hemoproteins. Broad.

Question 30

Properties of Human Cytochrome P450: Found mostly in the ________ but is also present in other tissues.

Answer 30

Liver

Question 31

A mitochondrial or ER enzyme. Activity may be induced or depressed by certain drugs, causing drug interactions.

Answer 31

Human Cytochrome P450

Question 32

Used to prevent blood clotting, is metabolized by a cytochrome which is induced by __________. Thus when both drugs induce are given, dose of this drug must be increased to achieve therapeutic doses.

Answer 32

Warfarin. Phenobarbital.

Question 33

Properties of Human Cytochrome P450: Exhibits genetic ________, so different individuals metabolize drugs differently.

Answer 33

Polymorphism

Question 34

Properties of Human Cytochrome P450: Activity is affected also by tissue or organ _________.

Answer 34

Disease (cirrhosis)

Question 35

Properties of Human Cytochrome P450: ________ is involved in the reaction mechanism.

Answer 35

NADPH

Question 36

Properties of Human Cytochrome P450: The preferred lipid in its structure is

Answer 36

Phosphatidylcholine

Question 37

Is a member of family 1 subfamily A and is the first individual member of the subfamily.

Answer 37

CYP1A1

Question 38

Response to _______ may be affected by age, sex and genetic factors. May result in cell injury, allergies or carcinogenesis.

Answer 38

Xenobiotics

Question 39

Genetic factors

Answer 39

Pharmacogenomics

Question 40

Reaction to drugs

Answer 40

Pharmacogenetics