Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN251)
DME Name Cytochrome P450 4A10 (Cyp4a1), Rattus norvegicus
Gene Name Cyp4a1
UniProt ID
CP4AA_RAT
EC Number    EC: 1.14.14.80     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.80
Lineage    Species: Rattus norvegicus     (Click to Show/Hide the Complete Species Lineage)
Kingdom: .
Phylum: .
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Genus: .
Species: Rattus norvegicus
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Tissue Distribution Expressed in liver (at protein level) and kidney (at protein level). .
Sequence
MSVSALSSTRFTGSISGFLQVASVLGLLLLLVKAVQFYLQRQWLLKAFQQFPSPPFHWFF
GHKQFQGDKELQQIMTCVENFPSAFPRWFWGSKAYLIVYDPDYMKVILGRSDPKANGVYR
LLAPWIGYGLLLLNGQPWFQHRRMLTPAFHYDILKPYVKNMADSIRLMLDKWEQLAGQDS
SIEIFQHISLMTLDTVMKCAFSHNGSVQVDGNYKSYIQAIGNLNDLFHSRVRNIFHQNDT
IYNFSSNGHLFNRACQLAHDHTDGVIKLRKDQLQNAGELEKVKKKRRLDFLDILLLARME
NGDSLSDKDLRAEVDTFMFEGHDTTASGVSWIFYALATHPEHQQRCREEVQSVLGDGSSI
TWDHLDQIPYTTMCIKEALRLYPPVPGIVRELSTSVTFPDGRSLPKGIQVTLSIYGLHHN
PKVWPNPEVFDPSRFAPDSPRHSHSFLPFSGGARNCIGKQFAMSEMKVIVALTLLRFELL
PDPTKVPIPLPRLVLKSKNGIYLYLKKLH
Function A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long-chain fatty acids . Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver . In kidney, may play an important role in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure . Also participates in the formation of anti-inflammatory hydroxyepoxyeicosatrienoic acids (HEETs) in kidney by converting 8,9-epoxyeicosatrienoic acid (EET) to 20,8,9-HEET, an activator of PPARA . Displays substantially lower fatty acid omega-1 hydroxylase activity . Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) .
Full List of Drug(s) Metabolized by This DME
      Preclinical/investigative Agents Click to Show/Hide the Full List of Drugs:          1 Drugs
Lauric acid
 Drug Info Investigative Alzheimer disease ICD11: 8A20 [1], [2]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR005370 12,12-Dihydroxydodecanoic Acid Dodecanedioic Acid Oxidation - Oxidationn Lauric acid [1], [2]
MR005369 12-Hydroxydodecanoic Acid 12,12-Dihydroxydodecanoic Acid Oxidation - Oxidationn Lauric acid [1], [2]
References
1 The omega-hydroxlyation of lauric acid: oxidation of 12-hydroxlauric acid to dodecanedioic acid by a purified recombinant fusion protein containing P450 4A1 and NADPH-P450 reductase
2 Cytochrome P450 4A11 inhibition assays based on characterization of lauric acid metabolites

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