Biotransformation and Elimination

Question 1

Biotransformation

Answer 1

the metabolic conversion of toxicants in the body

-depends on the properties of the compound and the dose

Question 2

Liver

Answer 2

site of detoxification

Question 3

Enzymes

Answer 3

• divided into four categories based on what they do to the target compound
• hydrolysis, reduction, oxidation, conjugation
• vary between species and different individuals and populations

Question 4

biotransformations occur in 3 phases

Answer 4

-converting the compounds to a hydrophilic form to facilitate transport out of the cell and the body

Question 5

phase i, ii, iii

Answer 5

-modified, conjugated, exported out of the cell

Question 6

phase i

Answer 6

• enzymes are either constitutively expressed or induced by exposure to a class of toxicant
• modification of the compound often by exposing or introducing a hydroxy, amine, thiol, or carboxyl through oxidation, reduction, or hydrolysis

Question 7

most common phase I enzyme

Answer 7

-cytochrome p450 or cyp enzymes

Question 8

cyp enzymes

Answer 8

• involved in oxidation
• adds oxygen molecular to a substrate
• endoplasmic reticulum of the liver
• catalyze reactions

Question 9

phase I general steps or reactions

Answer 9

• hydroxylation of an aliphatic or aromatic carbon
• epoxidation of a double bond
• heteroatom dealkylation

Question 10

epoxidation of a double bond

Answer 10

epoxide is transformed into a hydroxyl group

Question 11

heteroatom dealkylation

Answer 11

revealing a functional group for phase ii reactions

Question 12

phase ii

Answer 12

phase I metabolites are conjugated with or coupled to endogenous compounds to create more hydrophilic metabolites for excretion

Question 13

phase ii reactions

Answer 13

• glucuronidation
• sulfonation
• conjugation with glutathione
• conjugation with amino acids
• acetylation
• methylation

Question 14

metabolite

Answer 14

can lead to the toxic response

Question 15

metabolic activation

Answer 15

something is converted into a more reactive molecule

Question 16

phase iii

Answer 16

transport of the metabolites out of the cell

Question 17

transporters

Answer 17

• ABC transporters
• MRD/MDRs
• Solute carriers

Question 18

excretion

Answer 18

exit of toxicants and their biotransformed metabolites from a tissue

Question 19

elimination

Answer 19

the disappearance of a substance from the body

-urine, feces, exhalation, breast milk, sweat, saliva

Question 20

urinary excretion

Answer 20

• toxicants to kidneys through glomerular filtration and passive/active tubular secretion
• filtration=polar ions excreted in urine
• less polar into the kidney lumen
• active=OAT, MRD/MDRs

Question 21

fecal excretion

Answer 21

-bile=toxicants metabolized move into the bile for excretion into small intestine

Question 22

example of phase I and ii

Answer 22

absorption in GI tract, moves through liver, bound to albumin when circulating in the blood, excreted by the kidneys in urine

Question 23

active transport mechanisms

Answer 23

• require energy

- require ATP