Microsomal

Microsomal refers to anything related to microsomes, which are small vesicular fragments derived from the endoplasmic reticulum of cells. Microsomes are produced when whole cells are disrupted and the resulting homogenate is subjected to differential and ultracentrifugation, with the microsomal fraction typically collected as a pellet around 100,000 g. These vesicles arise from both rough and smooth endoplasmic reticulum and retain membrane-bound enzymes associated with ER functions.

The microsomal fraction is rich in enzymes involved in xenobiotic and endogenous metabolism. The best known component is the cytochrome P450 monooxygenase system, which includes various cytochrome P450 enzymes and the NADPH-cytochrome P450 reductase, along with auxiliary proteins such as cytochrome b5. In addition to Phase I oxidative enzymes, microsomes also contain certain Phase II conjugation enzymes, including UDP-glucuronosyltransferases, located on or near the ER membranes. The collective activity of these enzymes enables oxidation, reduction, hydrolysis, and conjugation reactions that modify a wide range of substrates, including drugs, toxins, steroids, and fatty acids.

In research and industry, microsomes are used to study metabolic pathways, determine substrate specificity and reaction kinetics, evaluate inhibitors, and assess metabolic stability of drug candidates in vitro. They provide a controlled system to explore enzyme activity and tissue-specific metabolism, particularly in liver-derived preparations. Limitations include the artificial nature of in vitro conditions, potential absence of cytosolic cofactors and transport processes, and variability between species and preparation methods, which can affect extrapolation to in vivo metabolism.