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Introductory remarks on human CYPs

This issue of Drug Metabolism Reviews is centered on the human P450 metabolism database compiled by Slobodan Rendic. With more than 3900 entries and over 1000 references, this database is a resource for studying the enzymology of the 57 known human P450 proteins. Presently, the database has entries on 42 of these P450s. Eleven of the enzymes have more than 100 entries each and CYP3A4 has 920 entries. The database has information related to substrates, inhibitors, and inducers. It is searchable by the drug name and the type of reaction catalyzed is given. This is one of several databases devoted to cytochrome P450, but it is unique in its emphasis on enzymology and metabolism. When future metadatabases are created by merger and hyper linking, this one will surely form a significant part of any online P450 encyclopedia. The set of human P450 genes and proteins is finite. At present there are 57 named P450s in humans (1) and this number is not expected to vary much in the future. The sequence of the human genome is nearly complete. The most recent figures at NCBI from Feb 11, 2001 show 32.5% finished, 61% draft, and 6.5% not represented yet in the genomic sequence data (2). These figures are 4 months old and they are certainly closer to completion now. It is satisfying to have a complete inventory of human P450 genes, but it must be understood that this is only a catalog. The more interesting properties of the P450s are their structure/function relationships and the phenotypes they produce when deleted, inhibited, or mutated. This information only comes through experimental work and it is hard to obtain. Fortunately, experimental work on the human P450s has been accumulating for several decades. The extensive Table 1 of Rendic (3) contains over 3900