ω-1 and ω-2 hydroxylation of prostaglandins by rabbit hepatic microsomal cytochrome P-450 isozyme 6

Karsten A. Holm, Dennis Koop, Minor J. Coon, Anthony D. Theoharides, David Kupfer

Research output: Contribution to journalArticle

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Abstract

Incubation of prostaglandin E1 (PGE1) with liver microsomes from control rabbits and from rabbits treated with ethanol or imidazole yielded 18-, 19-, and 20-hydroxy metabolites, representing hydroxylation at ω-2, ω-1, and ω carbons, respectively. The current investigation demonstrates that rabbit liver P-450 isozyme 6 effectively catalyzes the ω-1 andg w-2 hydroxylation of PGE1 and PGE2. Additionally, a small amount of product with Chromatographic characteristics of the corresponding 20-hydroxy metabolite has been detected. The incorporation of cytochrome b5 into the reconstituted system did not enhance the rate of PGE1 hydroxylation and had no effect on the ratio of products formed. The Km value for the ω-1 and ω-2 hydroxylation of PGE1 with P-450 isozyme 6 from imidazole-treated rabbits was approximately 140 μm; the Vmax's (nmol product min-1 nmol P-450-1) were 2.1 and 1.1 for the ω-1 and ω-2 hydroxylations, respectively. These rates represent the highest activities by hepatic P-450 isozymes for hydroxylation of PGs, and suggest that isozyme 6 is responsible for the ω-2 hydroxylation of PGEs observed in rabbit liver microsomes.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume243
Issue number1
DOIs
StatePublished - Nov 15 1985
Externally publishedYes

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Hydroxylation
Cytochrome P-450 Enzyme System
Isoenzymes
Prostaglandins
Rabbits
Alprostadil
Liver
Liver Microsomes
Metabolites
Cytochromes b5
Prostaglandins E
Dinoprostone
Ethanol
Carbon
Thermodynamic properties

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

ω-1 and ω-2 hydroxylation of prostaglandins by rabbit hepatic microsomal cytochrome P-450 isozyme 6. / Holm, Karsten A.; Koop, Dennis; Coon, Minor J.; Theoharides, Anthony D.; Kupfer, David.

In: Archives of Biochemistry and Biophysics, Vol. 243, No. 1, 15.11.1985, p. 135-143.

Research output: Contribution to journalArticle

Holm, Karsten A. ; Koop, Dennis ; Coon, Minor J. ; Theoharides, Anthony D. ; Kupfer, David. / ω-1 and ω-2 hydroxylation of prostaglandins by rabbit hepatic microsomal cytochrome P-450 isozyme 6. In: Archives of Biochemistry and Biophysics. 1985 ; Vol. 243, No. 1. pp. 135-143.
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