MetaCyc Polypeptide: cytochrome P450 2C19

Gene: CYP2C19 Accession Number: G-11686 (MetaCyc)

Species: Homo sapiens

Component of: melatonin O-demethylase

The cytochrome P450 enzymes are a superfamily of heme-containing monooxygenases found in eukaryotes, bacteria and archaea. They are divided into families and subfamilies based on their amino acid sequences. In mammals, cytochrome P450 enzymes are involved in many pathways including steroidogenesis and the metabolism of cholesterol and xenobiotics (reviewed in [Gonzalez92a]).

Enzyme commission comments for EC describe it as an unspecific monooxygenase capable of catalyzing a variety of reactions including hydroxylations and O-dealkylations, among others. This enzyme functions in conjunction with NADPH-hemoprotein reductase (EC

The cytochrome P450 isoforms involved in melatonin catabolism can vary with species, with differences shown between human and rat [Semak08].

Gene Citations: [Ma05, Romkes91]

Map Position: [96,522,463 -> 96,612,671]

Molecular Weight of Polypeptide: 55.931 kD (from nucleotide sequence)

Unification Links: Entrez-gene:1557 , PhosphoSite:P33261 , PhylomeDB:P33261 , Pride:P33261 , Protein Model Portal:P33261 , SMR:P33261 , String:9606.ENSP00000360372 , UniProt:P33261

Relationship Links: InterPro:IN-FAMILY:IPR001128 , InterPro:IN-FAMILY:IPR002401 , InterPro:IN-FAMILY:IPR017972 , PDB:Structure:4GQS , Pfam:IN-FAMILY:PF00067 , Prints:IN-FAMILY:PR00385 , Prints:IN-FAMILY:PR00463 , Prosite:IN-FAMILY:PS00086

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Created 09-Dec-2009 by Fulcher CA , SRI International

Subunit of: melatonin O-demethylase

Species: Homo sapiens

Subunit composition of melatonin O-demethylase = [POR][CYP2C19]
         NADPH-cytochrome P450 reductase = POR
         cytochrome P450 2C19 = CYP2C19 (summary available)

Created 09-Dec-2009 by Fulcher CA , SRI International

Enzymatic reaction of: melatonin O-demethylase

melatonin + a reduced flavoprotein + oxygen <=> N-acetyl-serotonin + an oxidized flavoprotein + formaldehyde + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of melatonin degradation , melatonin degradation I

Recombinant human cytochrome P450 isoforms were expressed, along with cytochrome P450 reductase, in insect cells and their NADPH-dependent melatonin 6-hydroxylation, or O-demethylation activities were assayed. Isoform CYP1A2 was concluded to be the major hepatic 6-hydroxylating isoform, while CYP1B1 was the major extrahepatic 6-hydroxylating isoform. CYP1A1 and CYP2C19 also catalyzed melatonin 6-hydroxylation, with the latter having a minor role [Ma05].

The O-demethylation of melatonin to N-acetyl-serotonin was primarily catalyzed by CYP2C19, with CYP1A2 playing a minor role [Ma05].


Gonzalez92a: Gonzalez FJ (1992). "Human cytochromes P450: problems and prospects." Trends Pharmacol Sci 13(9);346-52. PMID: 1529480

Ma05: Ma X, Idle JR, Krausz KW, Gonzalez FJ (2005). "Metabolism of melatonin by human cytochromes p450." Drug Metab Dispos 33(4);489-94. PMID: 15616152

Romkes91: Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily." Biochemistry 30(13);3247-55. PMID: 2009263

Semak08: Semak I, Korik E, Antonova M, Wortsman J, Slominski A (2008). "Metabolism of melatonin by cytochrome P450s in rat liver mitochondria and microsomes." J Pineal Res 45(4);515-23. PMID: 18717775

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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