Biotransformation Flashcards
Where does metabolism take place?
intestines, liver, lungs, kidneys, blood, placenta
What happens in phase I reactions and which types are there?
Change of functional group suitable for conjugation.
- Oxidation
- Hydrolysis
- Reduction
What are phase 1 enzymes?
CYP p450. Cytochrome p450
What is oxidation?
Reactions resulting in the addition of oxygen and/or the
removal of hydrogen
What are hydroxylation, S-oxidation, N-O-de-alkylation and Epoxidation?
hydroxylation: addition of O to form OH
S-oxidation: add O to S group
N-O-de-alkylation: deletion of CH to form OH
Epoxidation: ontstaat een bruggetje met O ertussen
What is aromatic hydroxylation?
additiion of OH to aromatic ring
What types of Oxidation are there?
dehydrogenases: hydrogen is removed
monoamine oxidase: break down neurotransmitters
peroxidase: in ER
How does metabolism of alcohol work?
Oxidation of alcohol –> acetaldehyde, followed by further oxidation of the
acetaldehyde –> acetate
What is hydrolysis?
A reaction with water that often involves splitting of the
molecule
What enzymes are involved in hydrolysis?
-esterases –> esters
-peptidases
-amidases
-cholinesterase –> acetylcholinesterase
What is reduction?
reaction resulting in addition of hydrogen AND/OR removal of oxygen
What are examples of reduction?
– R-OH ⇒ R-H (de-hydroxylation)
– R-C=O ⇒ R-C-OH (hydrogenation)
– R-COOH ⇒ R-C=O (decarboxylation)
– R-NO2⇒ R-NH2 (amination)
– R-C-H ⇒ R-CH3 (methylation)
What are enzymes involved in reduction reactions?
reductases
What is the goal of conjugation reactions?
-make polar group
-increase water solubility
-excretion
What are phase II reactions?
Conjugation reactions
What are examples of conjugation reactions?
Glucuronidation
Sulfation
Gluthathion conjugation
Acetylation
Methylation
Amino acid conjugation
What happens with Glucuronidation?
glucuronide is added and makes a compound more water soluble
What happens with sulfation?
Addition of SO3, NH2 or OH by sulfotransferases
What happens with glutathion conjugation?
Addition of S group by GST enzyme
Why is acetaminophen toxic?
Causes cell death
What happens with acetylation?
addition of COCH3 group
What factors influence biotransformation?
-food
-age
-environment
-health status
What is pharmacogenetics?
study of genetic differences in a populations
What is an enzyme inhibitor?
A molecule that binds to an enzyme on the active site to block its activity.
What is an noncompetitive enzyme inhibitor?
inhibitor binds to enzyme and alters the active site.
