PCL201H1 Lecture 18: Lecture 18 Biotransformation II
Document Summary
Reactions catalyzed by ctyochrome p450 have common features: insertion of o atom. Rh (substrate) + o2 + nadph (cofactor) + h+ roh + h2o + nadp+ (with the assistance of cytochrome p450 enzyme (a heme protein) Cytochrome p450 reaction: p450 with ferric iron binds to substrate, nadph cytochrome p450 reductase abstracts electron from nadph. The electron is transferred to oxygen: one oxygen atom goes to water: water is formed from 2 hydrogen atom input. Substrate is bound to (fe-o)3: carbon radical on substrate formed. Hydrogen from substrate moved to oxygen, forming a hydroxyl radical: joining of carbon radical with hydroxyl group forms (roh)fe3, splits, forming roh (hydroxylated product) and fe3+ (regenerated ferric ion) Cytochrome p450: integral membrane protein, closely associated with cytochrome p450 reductase. Reductase donates electrons to cyp, is rate limiting. Cyp: membrane bound enzyme, smooth er (especially liver) 4-52 biosynthetic reactions, metabolism of endogenous physiologic substrates, e. g. steroid hormones.
