BI12.1-3 | Xenobiotic, oxidative stress and antioxidants — Glossary

Any chemical foreign to the body's normal biochemistry, including drugs, environmental pollutants, dietary compounds, and food additives

The enzymatic conversion of lipophilic xenobiotics into hydrophilic metabolites for excretion, primarily occurring in the liver

Functionalisation reactions that introduce or expose a functional group (-OH, -NH2, -SH, -COOH) on the xenobiotic, primarily catalysed by CYP450

Conjugation reactions that attach a large polar molecule (glucuronate, sulphate, glutathione) to the Phase I product for excretion

A superfamily of haem-containing monooxygenases in the smooth ER that catalyse Phase I oxidation reactions; CYP3A4 metabolises approximately 50% of all drugs

The single most important drug-metabolising CYP450 isoform, responsible for metabolising approximately 50% of all prescribed drugs

Increased CYP450 enzyme synthesis caused by inducers (e.g., rifampicin) via nuclear receptor activation, leading to faster drug metabolism and potential therapeutic failure

Decreased CYP450 activity caused by inhibitors (e.g., ketoconazole) blocking the active site, leading to drug accumulation and potential toxicity

N-acetyl-p-benzoquinone imine — the highly reactive toxic metabolite of paracetamol produced by CYP2E1, normally detoxified by glutathione conjugation

The most common Phase II conjugation reaction, catalysed by UGT enzymes using UDP-glucuronic acid as the donor molecule

Any chemical species with one or more unpaired electrons in its outer orbital, making it highly reactive and capable of damaging biological molecules

Oxygen-derived molecules including superoxide, hydrogen peroxide, and hydroxyl radical that can cause oxidative damage to cellular components

The enzymatic antioxidant that converts superoxide radical to hydrogen peroxide; exists as three isoforms (SOD1, SOD2, SOD3)

The peroxisomal enzyme that decomposes hydrogen peroxide to water and oxygen, with a turnover rate of 40 million molecules per second

A selenium-dependent enzyme that reduces hydrogen peroxide and lipid hydroperoxides using GSH as the electron donor

The most abundant intracellular thiol antioxidant (gamma-Glu-Cys-Gly); depleted in paracetamol toxicity; regenerated by glutathione reductase requiring NADPH

X-linked deficiency of glucose-6-phosphate dehydrogenase causing inadequate NADPH production, inability to regenerate GSH, and oxidative haemolysis

A chain reaction where ROS abstract hydrogen atoms from PUFAs in cell membranes, producing lipid radicals, peroxyl radicals, and toxic end products (MDA, 4-HNE)

8-hydroxydeoxyguanosine — an oxidative DNA damage product and biomarker, causing G:C to T:A transversion mutations

The reaction of ferrous iron (Fe2+) with H2O2 producing the highly reactive hydroxyl radical (•OH); explains why free iron is toxic

The theory that oxidation of LDL in the arterial intima is a key initiating event in atherosclerosis, promoting foam cell formation

The antidote for paracetamol overdose; a prodrug of cysteine that replenishes hepatic glutathione stores to detoxify NAPQI

An end product of lipid peroxidation used as a biomarker of oxidative stress, measured by the TBARS assay

Macrophage receptors (SR-A, CD36) that take up oxidised LDL without cholesterol-mediated feedback inhibition, leading to foam cell formation

The metabolic conversion of a non-toxic xenobiotic to a more toxic or reactive metabolite, as in CYP2E1 conversion of paracetamol to NAPQI