Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase.

Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Research Abstract Details 

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Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Abstract Text:

Li Li,Todd D Porter,

Squalene monooxygenase is a microsomal enzyme that catalyzes the conversion of squalene to 2,3(s)-oxidosqualene, the immediate precursor to lanosterol in the cholesterol biosynthesis pathway. Unlike other flavoprotein monooxygenases that obtain electrons directly from NAD(P)H, squalene monooxygenase requires a redox partner, and for many years it has been assumed that NADPH-cytochrome P450 reductase is this requisite redox partner. However, our studies with hepatic cytochrome P450-reductase-null mice have revealed a second microsomal reductase for squalene monooxygenase. Inhibition studies with antibody to P450 reductase indicate that this second reductase supports up to 40% of the monooxygenase activity that is obtained with microsomes from normal mice. Studies carried out with hepatocytes from CPR-null mice demonstrate that this second reductase is active in whole cells and leads to the accumulation of 24-dihydrolanosterol; this lanosterol metabolite also accumulates in the livers of CPR-null mice, indicating that cholesterol synthesis is blocked at lanosterol demethylase, a cytochrome P450.

Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Publishing Authors By Initials

L Li,TD Porter,

For similar enzymes and coenzymes: enzymes: oxidoreductases: oxygenases: mixed function oxygenases: squalene monooxygenase research abstracts see: enzymes and coenzymes: enzymes: oxidoreductases: oxygenases: mixed function oxygenases: squalene monooxygenase research

PUBMED ID PMID:

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Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Archives of biochemistry and biophysics

VOLUME: 461

Page Numbers: 76-84

Journal Abbreviation:

ISSN: 0003-9861

DAY: 2

MONTH: 03

YEAR: 2007

Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372430

Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Keywords Mesh Terms:

KEYWORDS: Squalene Monooxygenase

MESH TERMS: physiology

Chemical & Substance for Abstract: Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Information

Substance Name: NADPH-Ferrihemoprotein Reductase

Registry Number: EC 1.6.2.4

Grant and Affiliation Information for Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase.

AFFILIATION: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: ES07462

ACRONYM: ES

MEDLINETA: Arch Biochem Biophys

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