Metabolization

Metabolization, often referred to as biotransformation, is the chemical modification of substances by living organisms. In humans, it primarily serves to convert lipophilic compounds—such as drugs, environmental chemicals, and endogenous substances—into more polar, water-soluble forms that can be more readily excreted.

Most metabolization occurs in the liver, though tissues such as the intestine, kidneys, lungs, skin, and blood vessels also participate. Metabolic processes are usually categorized as Phase I reactions, which introduce or unmask functional groups (for example oxidation, reduction, hydrolysis), and Phase II reactions, which attach polar groups through conjugation (for example glucuronidation, sulfation, glutathione conjugation).

The principal enzymes are in the cytochrome P450 family, but many others contribute, including flavin-containing monooxygenases, esterases, amidases, and transferases. These reactions can detoxify compounds, but can also activate prodrugs or generate reactive metabolites that may cause toxicity.

Clinical relevance includes effects on drug exposure and safety. First-pass metabolism reduces oral bioavailability; genetic variability leads to different drug levels; enzyme induction or inhibition by other substances can alter metabolization rates. Examples: caffeine is metabolized by CYP1A2; codeine is a prodrug converted to morphine; acetaminophen can form a reactive metabolite that can cause liver injury at high doses.

Study and measurement: pharmacokinetics assess clearance and half-life; in vitro systems such as liver microsomes or hepatocytes are used to study enzyme activity; in vivo studies examine whole-body processing.