Biotransformation and Elimination Flashcards
Biotransformation
the metabolic conversion of toxicants in the body
-depends on the properties of the compound and the dose
Liver
site of detoxification
Enzymes
- 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
biotransformations occur in 3 phases
-converting the compounds to a hydrophilic form to facilitate transport out of the cell and the body
phase i, ii, iii
-modified, conjugated, exported out of the cell
phase i
- 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
most common phase I enzyme
-cytochrome p450 or cyp enzymes
cyp enzymes
- involved in oxidation
- adds oxygen molecular to a substrate
- endoplasmic reticulum of the liver
- catalyze reactions
phase I general steps or reactions
- hydroxylation of an aliphatic or aromatic carbon
- epoxidation of a double bond
- heteroatom dealkylation
epoxidation of a double bond
epoxide is transformed into a hydroxyl group
heteroatom dealkylation
revealing a functional group for phase ii reactions
phase ii
phase I metabolites are conjugated with or coupled to endogenous compounds to create more hydrophilic metabolites for excretion
phase ii reactions
- glucuronidation
- sulfonation
- conjugation with glutathione
- conjugation with amino acids
- acetylation
- methylation
metabolite
can lead to the toxic response
metabolic activation
something is converted into a more reactive molecule
phase iii
transport of the metabolites out of the cell
transporters
- ABC transporters
- MRD/MDRs
- Solute carriers
excretion
exit of toxicants and their biotransformed metabolites from a tissue
elimination
the disappearance of a substance from the body
-urine, feces, exhalation, breast milk, sweat, saliva
urinary excretion
- 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
fecal excretion
-bile=toxicants metabolized move into the bile for excretion into small intestine
example of phase I and ii
absorption in GI tract, moves through liver, bound to albumin when circulating in the blood, excreted by the kidneys in urine
active transport mechanisms
- require energy
- require ATP