Cashman John R, Zhang Jun
Human BioMolecular Research Institute, San Diego, CA 92121, USA.
Annu Rev Pharmacol Toxicol. 2006;46:65-100. doi: 10.1146/annurev.pharmtox.46.120604.141043.
This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
本综述总结了有关人类含黄素单加氧酶（FMO，EC 1.14.13.8）的药理学和毒理学意义的最新信息。人类FMO使含亲核杂原子的化学物质和药物氧化，并通常将它们转化为无害的、极性的、易于排泄的代谢产物。然而，有时FMO会将化学物质生物活化成具有毒性的反应性物质。FMO的个体差异大多归因于基因变异性和等位基因变异，剪接变体可能导致FMO介导的代谢存在个体间和种族间的差异。与细胞色素P450（CYP）不同，FMO不易被诱导也不易被抑制，对于主要由FMO代谢的药物，潜在的不良药物相互作用被降至最低。这些特性可能在药物设计和发现中具有优势，通过将FMO解毒途径纳入候选药物，可能会出现更多类似药物的物质。尽管没有详尽的例子，但生理因素可影响FMO功能，这可能对FMO的临床意义及其在人类疾病中的作用产生影响。
