Drug metabolism by cytochrome p450 enzymes: what distinguishes the pathways leading to substrate hydroxylation over desaturation?

摘要: Cytochrome P450 enzymes are highly versatile biological catalysts in our body that react with a broad range of substrates. Key functions the liver include metabolism drugs and xenobiotics. One particular metabolic pathway is poorly understood relates to activation aliphatic groups leading either hydroxylation or desaturation pathways. A DFT QM/MM study has been carried out on factors determine regioselectivity over compounds by isozymes. The calculations establish multistate reactivity patterns, whereby product distributions differ each spin-state surfaces; hence spin-selective formation was found. electronic thermochemical bifurcation pathways were analysed model predicts established from valence bond molecular orbital theories. Thus, difference energy OH versus OC formed π-conjugation determines degree products. In addition, environmental effects substrate binding pocket affect regioselectivities identified. These studies imply bioengineering isozymes for reactions will have modifications restrict rebound reaction.