cytochrome P450-lecture 19

cytochrome is what kind on enzyme?

monooxygenase enzyme

cytochrome P450 isozymes are—

heme-thiolate proteins (with iron and sulfur) that are synthesized in the liver

where are CYP450 located

mainly in the liver but can be found elsewhere

isozymes

group of enzymes that catalyze the same reaction but have different structures

where is the highest structural conservation found?

in the core of the protein around the heme causing the mechanism of electron transfer and oxygen activation

P450 are-

type-b hemoproteins with a porphyrin ring and iron atom in the center

CYP2D6

cytochrome P450 enzyme

CYP2D6

family

CYP2D6

sub-family

CYP2D6

sequence of discovery

how does CYP450 function?

it is organ specific

• liver, lungs, and small intestine metabolize drugs

• placental= steroid hormone

• kidneys= vitamin d3 cholecalciferol

liver drug metabolism phase I

drug is altered/broken down into intermediate metabolites

liver drug metabolism phase II

intermediate metabolites conjugate and becomes more soluble and expells from body in urine

the breakdown/alteration of drugs in phase II is catalyzed by CYP450 enzymes

false, it is in phase I

Catalyzing reaction equation

R-H + O2+ NADPH + H(+) ——> R-OH + H20+ NADP(+)

how do CYP450 inducers increase activity?

by increasing enzyme synthesis

what is the result of induction?

accelerated drug metabolism by targeted enzyme

how do inhibitors decrease enzyme activity by?

by inhibiting enzyme synthesis

what is the result of inhibiton?

reduction of drug metabolism by targeted drug

induction/inhibition can cause?

drug-drug interactions/adverse reactions

polymorphism

hereditary genetic variability among humans in their ability to metabolize drugs

gain-to-function

needs more to work because it metabolizes too quickly (ultra extensive)

loss-of-function

fewer enzymes needed to work (poor metabolizer)

the normal population is what kind of metabolizer?

extensive metabolizers

CYP3A4

largest and flexible family that can accommodate many compounds