microsome

Microsomes are vesicle-like fragments derived from the endoplasmic reticulum of cells. They form when a tissue is homogenized and the resulting mixture is subjected to differential centrifugation, yielding small, closed membrane vesicles that retain ER-associated proteins. Two main subtypes exist: rough microsomes, which still bear ribosomes on their cytosolic surface, and smooth microsomes, which are depleted of ribosomes.

Biochemical composition and function center on enzymes associated with the ER, most notably the cytochrome P450 monooxygenase system and the NADPH-cytochrome P450 reductase. These systems drive phase I oxidative reactions such as hydroxylation, dealkylation, and other transformations important for xenobiotic and drug metabolism. Some microsomal preparations also contain enzymes involved in phase II processes, such as UDP-glucuronosyltransferases, though their activity depends on vesicle orientation and cofactors.

Uses and applications include in vitro studies of drug metabolism, enzyme kinetics, and the effects of inhibitors or inducers on ER-bound enzymes. Microsomes enable rapid assessment of substrate specificity and metabolic pathways, often using human liver microsomes to model human pharmacokinetics. They can be used to reconstitute P450 systems or to study interactions with various cofactors and modulators, under controlled NADPH-generating conditions.

Limitations and considerations include the absence of intact cellular context, potential orientation effects of luminal enzymes, and species or tissue differences that may limit extrapolation to in vivo metabolism. Microsomal preparations require careful handling and storage to preserve enzymatic activity.