Studies on the oxidation of ω-hydroxyprostaglandins by an NAD-dependent dehydrogenase from mammalian liver cytosol

David Kupfer, Javier Navarro, Gregory K. Miranda, Daniel E. Piccolo, Anthony Theoharides

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The oxidation of 12-hydroxylauric acid methyl ester (12-OH-L-Me) and of ω-hydroxy-prostaglandins (ω-OH-PGs) such as 20-OH-PGB1 and 20-OH-PGE1, was demonstrated with liver cytosol from rat, rabbit, and guinea pig in the presence of NAD; however, NADP did not support this oxidation. (ω-1)-Hydroxy-compounds (11-OH-laurate and 19-OH-PGB1) and PGE1, PGF, and PGB1, all lacking the terminal (ω)-hydroxyl, did not reduce NAD. However, at pH 10, PGE1 slightly enhanced NAD reduction, suggesting that at this pH PGE1, could be a substrate for 15-hydroxy-PG dehydrogenase (PGDH). The oxidation products from incubations of 12-OH-L-Me, 20-OH-PGB1-Me, and 20-OH-PGE1 with guinea pig liver cytosol were isolated and identified by gas chromatography/mass fragmentation spectrometry as being the corresponding dicarboxylic acids. In contrast to the liver cytosol, guinea pig kidney cytosol had only a minimal effect on NAD reduction by 12-OH-L-Me but nevertheless did support the stimulation of NAD reduction by PGE1, and PGF, but not by PGB1, indicating the participation of kidney cytosolic PGDH in PGE1 and PGF oxidation and demonstrating that the oxidation of ω-OH to the carboxylic acid is not mediated by PGDH. Though the in vivo rate of oxidation of ω-OH-PGs has not been established, these results suggest that the urinary dicarboxylic-PG metabolites involve a multiple sequentialstep oxidation of PGs involving ω-hydroxylation by an NADPH-cytochrome P-450 system in the endoplasmic reticulum and the subsequent oxidation of the ω-OH by an NAD-dependent dehydrogenase in the cytosol.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume199
Issue number1
DOIs
StatePublished - 1980
Externally publishedYes

Fingerprint

Liver
NAD
Cytosol
Oxidoreductases
Alprostadil
15-hydroxyprostaglandin dehydrogenase
Oxidation
Guinea Pigs
NADP
Laurates
hydroxide ion
Kidney
Dicarboxylic Acids
Hydroxylation
Metabolites
Carboxylic Acids
Endoplasmic Reticulum
Gas chromatography
Hydroxyl Radical
Gas Chromatography-Mass Spectrometry

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Studies on the oxidation of ω-hydroxyprostaglandins by an NAD-dependent dehydrogenase from mammalian liver cytosol. / Kupfer, David; Navarro, Javier; Miranda, Gregory K.; Piccolo, Daniel E.; Theoharides, Anthony.

In: Archives of Biochemistry and Biophysics, Vol. 199, No. 1, 1980, p. 228-235.

Research output: Contribution to journalArticle

Kupfer, David ; Navarro, Javier ; Miranda, Gregory K. ; Piccolo, Daniel E. ; Theoharides, Anthony. / Studies on the oxidation of ω-hydroxyprostaglandins by an NAD-dependent dehydrogenase from mammalian liver cytosol. In: Archives of Biochemistry and Biophysics. 1980 ; Vol. 199, No. 1. pp. 228-235.
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