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Environmental Toxicology > Chapter 9 - Transformation of Contaminants > Flashcards

Chapter 9 - Transformation of Contaminants Flashcards

1
Q

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

A

biotransformation

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2
Q

focus area of toxicokinetics

A
  • biotransformation
  • absorption
  • distribution
  • storage
  • elimination
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3
Q

host factors which affect biotransformation

A
  • age
  • sex
  • existing disease
  • genetic variability
  • enzyme variability
  • nutritional status
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4
Q

ability to metabolize a toxicant can vary with ____

A

age

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5
Q

Why would infants have limited britransformation?

A

they lack important enzymes

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6
Q

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

A

young adulthood

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7
Q

Why would the elderly have difficulties with biotransformation?

A

functional loss with aging

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8
Q

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

A

early adulthood

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9
Q

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

A

hormones

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10
Q

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

A

nutritional status

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11
Q

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

A

liver

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12
Q

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

A

enzymes

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13
Q

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

A

phenylketonuria

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14
Q

What is the treatment for individuals diagnosed with phenylketonuria?

A
  • diet that restricts intake of foods containing phenylalanine
  • use artificial sweeteners
    ** if not, mental retardation may result
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15
Q

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

A

incorrect “proper fit” or induced fit

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16
Q

What do alcohols have in common?

A

share a common hydroxyl group

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17
Q

What enzyme metabolizes alcohol?

A

alcohol dehydrogenase

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18
Q

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

A

metabolites differ

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19
Q

Chemicals are detoxified by which processes?

A
  • rendering them less harmful
  • making them more water soluble
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20
Q

What enzyme converts chloroform into phosgene?

A

P450

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21
Q

Which is more toxic?
chloroform or phosgene

A

phosgene

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22
Q

Different enzymes may ____ for the same toxicant.

A

compete

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23
Q

Aniline can form what two metabolites?

A
  • phenylhdroxylamine
  • p-aminophenol
24
Q

enzyme that transforms analine into p-aminophenol

A

P450

25
Q

enzyme that transforms aniline into phenylhydroxylamine

A

n-hydroxylase

26
Q

Which is more toxic?
phenylhdroxylamine or p-aminophenol

A

phenylhdroxylamine

27
Q

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

A

liver

28
Q

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

A

lungs and kidneys

intestines, placenta, skin

29
Q
A
30
Q

organelle where enzymes are found

A

endoplasmic reticulum

31
Q

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

A

microsome

32
Q

where are microsomes the most present in the body?

A

liver

33
Q

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

A

hydrolases, reductases, carboxylesterases

34
Q

very large superfamily of hemoproteins found in all domains of life

A

cytochrome P450 (CYP450)

35
Q

what metal group does CYP450 contain?

A

heme group

36
Q

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

A
  • oxidation
  • reduction
  • hydrolysis
37
Q

loss of electrons, removal of hydrogen

A

oxidation

38
Q

gain of electrons

A

reduction

38
Q

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

A

hydrolysis

39
Q

process which results in an increased ability to metabolize toxicants

A

enzyme induction

40
Q

examples of phase 1 enzymes

A
  • epoxide hydrolases
  • flavin-containing monooxygenases
  • amidases and esterases
  • lipoxygenase
41
Q

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

A

oxidative stress

42
Q

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

A

intermediate metabolite

43
Q

intermediate metabolites contain “polar handle” which as what groups?

A
  • carboxyl
  • amino
  • hydroxyl
44
Q

what are phase 2 reactions also known as?

A

conjugation reactions

45
Q
  • 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
A

glutathione S-tranferase (GST)

46
Q

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

A

glutathione (GSH)

47
Q

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

A

GST

48
Q

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

A

acetominophen toxicity

49
Q

what is phase 1 of acetaminophen bioremediation?

A

mediated by cytochrome CYP2E1, produces hepatotoxic metabolite: NAPQI

50
Q

what is phase 2 of acetaminophen biotransformation

A

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

51
Q

what can large does of acetaminophen do to the body?

A

it can overwhelm the conugating enzymes and result in toxicity

52
Q

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

A

isoniazid

mediated via N-acetyl-transferase

53
Q

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).

A

50, 1

“fast acetylators”

54
Q

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

A

3

“slow acetylators”

55
Q

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?

A

slow acetylators

Environmental Toxicology (9 decks)

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