Chapter 9 - Transformation of Contaminants

Question 1

the sum of all chemical processes of the body that modify endogenous or exogenous chemicals

Answer 1

biotransformation

Question 2

focus area of toxicokinetics

Answer 2

• biotransformation
• absorption
• distribution
• storage
• elimination

Question 3

host factors which affect biotransformation

Answer 3

• age
• sex
• existing disease
• genetic variability
• enzyme variability
• nutritional status

Question 4

ability to metabolize a toxicant can vary with ____

Answer 4

age

Question 5

Why would infants have limited britransformation?

Answer 5

they lack important enzymes

Question 6

At what point do enzymes reach their optimal capacity for biotransformation in humans?

Answer 6

young adulthood

Question 7

Why would the elderly have difficulties with biotransformation?

Answer 7

functional loss with aging

Question 8

When are enzyme fluctions the highest in the lifetime of a human?

Answer 8

early adulthood

Question 9

What is an example of gender-specific variability in biotransformation?

Answer 9

hormones

Question 10

What is an impacting factor for biotransformation including minerals and vitamins?

Answer 10

nutritional status

Question 11

What organ is very important for biotransformation and must be free from disease?

Answer 11

liver

Question 12

biological catalysts and high-molecular weight proteins that allow biotransformation rates to proceed

Answer 12

enzymes

Question 13

What is the disease called which infants are born with that converts the amino acid phenylalanine to tyrosine?

Answer 13

phenylketonuria

Question 14

What is the treatment for individuals diagnosed with phenylketonuria?

Answer 14

• diet that restricts intake of foods containing phenylalanine
• use artificial sweeteners
  ** if not, mental retardation may result

Question 15

When dealing withe substrate and reaction sites, what can cause a problem with biotransformation?

Answer 15

incorrect “proper fit” or induced fit

Question 16

What do alcohols have in common?

Answer 16

share a common hydroxyl group

Question 17

What enzyme metabolizes alcohol?

Answer 17

alcohol dehydrogenase

Question 18

Once alcohol is metabolized, what can differ in its toxicity depending on the kind of alcohol metabolized?

Answer 18

metabolites differ

Question 19

Chemicals are detoxified by which processes?

Answer 19

• rendering them less harmful
• making them more water soluble

Question 20

What enzyme converts chloroform into phosgene?

Answer 20

P450

Question 21

Which is more toxic?
chloroform or phosgene

Answer 21

phosgene

Question 22

Different enzymes may ____ for the same toxicant.

Answer 22

compete

Question 23

Aniline can form what two metabolites?

Answer 23

• phenylhdroxylamine
• p-aminophenol

Question 24

enzyme that transforms analine into p-aminophenol

Answer 24

P450

Question 25

enzyme that transforms aniline into phenylhydroxylamine

Answer 25

n-hydroxylase

Question 26

Which is more toxic? phenylhdroxylamine or p-aminophenol

Answer 26

phenylhdroxylamine

Question 27

Which organ has the highest capacity for entering into reaction because of its high concentration of enzymes?

Answer 27

liver

Question 28

Which organs have about a 5th of the biotransformation capcacity of the liver?

Answer 28

lungs and kidneys | intestines, placenta, skin

Question 30

organelle where enzymes are found

Answer 30

endoplasmic reticulum

Question 31

mixture of fragmented endoplasmic reticulum vesicles present in a cell homogenate after mechanical breakage

Answer 31

microsome

Question 32

where are microsomes the most present in the body?

Answer 32

liver

Question 33

what are other enzymes which are important for biotransformation of toxicants?

Answer 33

hydrolases, reductases, carboxylesterases

Question 34

very large superfamily of hemoproteins found in all domains of life

Answer 34

cytochrome P450 (CYP450)

Question 35

what metal group does CYP450 contain?

Answer 35

heme group

Question 36

what are the three main types of phase 1 biotransforamtion reactions?

Answer 36

* oxidation * reduction * hydrolysis

Question 37

loss of electrons, removal of hydrogen

Answer 37

oxidation

Question 38

gain of electrons

Answer 38

reduction

Question 38

splitting of a toxicant molecule into smaller molecules through the addition of water

Answer 38

hydrolysis

Question 39

process which results in an increased ability to metabolize toxicants

Answer 39

enzyme induction

Question 40

examples of phase 1 enzymes

Answer 40

* epoxide hydrolases * flavin-containing monooxygenases * amidases and esterases * lipoxygenase

Question 41

the metabolism of xenobiotics generates free radicals. this increases ____ and can result in cellular damage.

Answer 41

oxidative stress

Question 42

xenobiotics that are done with phase 1 biotransformation reaction produce what?

Answer 42

intermediate metabolite

Question 43

intermediate metabolites contain "polar handle" which as what groups?

Answer 43

* carboxyl * amino * hydroxyl

Question 44

what are phase 2 reactions also known as?

Answer 44

conjugation reactions

Question 45

* found in the cytosol and microsomal membrane bound * homo- or hetero-dimeric enzymes * mediate conjugation of electrophilic toxicants using glutathione GSH * result is less reactive and more water-soluble that can be excreted

Answer 45

glutathione S-tranferase (GST)

Question 46

tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine

Answer 46

glutathione (GSH)

Question 47

glutathione and xenobiotic react via ____ to form glutathione-S-conjugate

Answer 47

GST

Question 48

what is an example of the importance of balance between phase 1 and 2 reactions?

Answer 48

acetominophen toxicity

Question 49

what is phase 1 of acetaminophen bioremediation?

Answer 49

mediated by cytochrome CYP2E1, produces hepatotoxic metabolite: NAPQI

Question 50

what is phase 2 of acetaminophen biotransformation

Answer 50

used **sulfotransferase** and **glucuronyl transferase** to form the sulfate and **glucuronide** conjugation products of **NAPQI** that can be readily eliminated by the body

Question 51

what can large does of acetaminophen do to the body?

Answer 51

it can overwhelm the conugating enzymes and result in toxicity

Question 52

drug used in the treatment of tuberculosis and is detoxified through the addition of an acetyl grouo onto the molecule

Answer 52

isoniazid | mediated via N-acetyl-transferase

Question 53

individuals that have a normal form of N-acetly-transferase can eliminate a dose of isoniazid can eliminate a dose by ____% in approximately ____ hour(s).

Answer 53

50, 1 | "fast acetylators"

Question 54

individuals who have a mutation for the enzyme N-acetly-transferase can eliminate a dose of isoniazid in ____ hour(s)

Answer 54

3 | "slow acetylators"

Question 55

individual response on a genetic level can leave an individual at greater risk of developing cancers, who are at most risk for this to happen?

Answer 55

slow acetylators