TOX - Biotransformation Pt. 1

Biotransformation Overview

• Process converting hydrophobic substances to hydrophilic for easier elimination from the body.

• Metabolites are chemically distinct from original compounds and are more hydrophilic.

Tissue Capacities

• Low Capacity: Skin, testes, placenta.

• Medium Capacity: Intestines, kidneys, lungs.

• Highest Capacity: Liver.

• Goal is detoxification, but bioactivation can occur, leading to more toxic metabolites.

Biotransformation Reactions

• Phase I: Hydrolysis, oxidation, reduction. Involves exposing functional groups.

• Phase II: Conjugations that increase hydrophilicity, aiding in elimination.

Major Enzymes Involved

• Phase I: Cytochrome P450, Flavin Monooxygenases, Dehydrogenases, Amine Oxidases, Esterases.

• Phase II: Glutathione transferases, Glucuronyl transferases, Sulfotransferases.

Cytochrome P450 Functionality

• Superfamily of enzymes, primarily in liver and membrane-bound (endoplasmic reticulum).

• Responsible for metabolism of drugs, xenobiotics, and endogenous compounds.

Common Reactions in Biotransformation

• Important Phase I Reactions: Epoxidation, hydroxylation, N-dealkylation, O-dealkylation, S-oxidation, dehalogenation, etc.

• Cytoplasmic Oxidation: Alcohol Dehydrogenase, Aldehyde Dehydrogenase, Amine oxidases, Esterases.

Biological Half-life

• Rate of toxicant removal is linked to biotransformation and elimination rates, determining biological half-life (T1/2).