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Literature summary for 1.14.14.1 extracted from

  • Flueck, C.E.; Mullis, P.E.; Pandey, A.V.
    Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism (2010), Biochem. Biophys. Res. Commun., 401, 149-153.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
NADPH-P450 reductase supports the CYP3A4 activity through providing NADPH, mutations in NADPH-P450 reductase, identified in patients with disordered steroidogenesis/Antley-Bixler syndrome, reduce CYP3A4 activity. NADPH-P450 reductase mutants Y181D, A457H, Y459H, V492E and R616X loose more than 99% of CYP3A4 activity, while NADPH-P450 reductase mutations A287P, C569Y and V608F loose 60-85% activity Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression in Escherichia coli Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ heme protein Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
quinine + [reduced NADPH-hemoprotein reductase] + O2 Homo sapiens in the microsomal membranes, CYP3A4 interacts with the NADPH-P450 reductase to receive electrons used in metabolism of drugs and xenobiotics. The heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions 3-hydroxyquinine + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli by anion exchange chromatography and gel filtration to homogeneity Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
quinine + [reduced NADPH-hemoprotein reductase] + O2
-
Homo sapiens 3-hydroxyquinine + [oxidized NADPH-hemoprotein reductase] + H2O
-
?
quinine + [reduced NADPH-hemoprotein reductase] + O2 in the microsomal membranes, CYP3A4 interacts with the NADPH-P450 reductase to receive electrons used in metabolism of drugs and xenobiotics. The heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions Homo sapiens 3-hydroxyquinine + [oxidized NADPH-hemoprotein reductase] + H2O
-
?

Synonyms

Synonyms Comment Organism
CYP3A4
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Homo sapiens
cytochrome P450 3A4
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FMN the heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions Homo sapiens
heme the heme unit in CYP3A4 is the catalytic center and electrons are transferred through reduced FMN to heme through electrostatic interactions Homo sapiens
NADPH required, supplied by the NADPH-P450 reductase Homo sapiens

Expression

Organism Comment Expression
Homo sapiens mutations in NADPH-P450 reductase, identified in patients with disordered steroidogenesis/Antley-Bixler syndrome, reduce CYP3A4 activity. NADPH-P450 reductase mutants Y181D, A457H, Y459H, V492E and R616X loose more than 99% of CYP3A4 activity, while NADPH-P450 reductase mutations A287P, C569Y and V608F loose 60-85% activity down

General Information

General Information Comment Organism
additional information loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with NADPH-P450 reductase mutations Homo sapiens