The molecular oxygen binds to ferrous P450, forming a ferrous CYP–dioxygen complex, and the second electron is transferred from CPR to the ferrous CYP–dioxygen complex, forming the peroxo complex, and this complex is rapidly protonated twice to form one molecule of water and an iron–oxo complex. The organic substrate (R) binds to the heme group of the enzyme and this binding allows the transfer of an electron from NADPH through cytochrome P450 reductase (CPR) to the hem domain that reduces the iron (Fe) from the ferric state (Fe 3+) to the ferrous state (Fe 2+). NAD(P)H supplies electron equivalents through an electron transfer chain that involves different redox partners, the nature of which is utilized to classify cytochromes P450 into 10 classes. RH + O 2 + NAD(P)H + H + → ROH + H 2O + NAD(P) + Often, alterations in specific P450s affect the biological processes that they mediate, leading to a disease. Human P450 enzymes metabolize drugs and synthesize endogenous compounds essential for human physiology. The features and functions of P450 enzymes have been studied from bacteria to mammals (see, accessed on 15 November 2022). CYPs are classified into families on the basis of the sequence identity of their amino acid sequences, and the symbol CYP is the root followed by an Arabic numeral representing family therefore, the subfamily is indicated by a letter and the gene is represented by a number. The non-A-type P450 enzymes form distinct clades and are more closely related to non-plant P450 enzymes than to the A-type. Plant P450s are classified into the A-type group and are involved in plant-specific biochemical pathways. CYPs are ancient enzymes that are extensively diffused in the organisms of all kingdoms of life ( Figure 1), including viruses, with the largest number of P450 genes being present in plants. The heme group plays essential roles in catalysis, providing the P450s’ carbon monoxide-binding ability moreover, the signature sequence FxxGxxxCxG in the heme-binding domain functions as the fifth ligand to the heme iron. A few years later, it was demonstrated that this pigment is a heme-containing protein, and it was called “P-450” (P for pigment). These enzymes were discovered in 1958, while studying the spectrophotometric properties of pigments in a microsomal fraction of rat livers.
CYPs are a large superfamily of enzymes that show an absorbance peak at 450 nm when their heme is reduced and complexed with carbon monoxide. Radicals or reactive oxygenated intermediates generated by CYPs can also lead to the formation of oxidative C–C bond cleavage, dealkylation, desaturation, dehydration, the oxidative rearrangement of carbon skeletons, and decarboxylation. The CYP-mediated molecular oxygen activation gives rise to ketones, alcohols, aldehydes, epoxides, and carboxylic acids. Cytochromes P450 Enzymes: General FeaturesĬytochromes P450 (P450s or CYPs) are heme–thiolate terminal monooxygenases that transfer one atom from molecular oxygen to X–H bonds, where X may be the -C, -N, or S of a substrate, with a concomitant reduction in the remaining oxygen atom to water.
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