Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer

Journal Article · Fri Oct 25 04:00:00 EDT 1985 · J. Biol. Chem.; (United States)

OSTI ID:6085071

Liston, T E; Roberts, L.J. 2d.

50 microCi of (TH)prostaglandin D2 tracer (100 Ci/mmol) was infused intravenously into a normal human male volunteer. 75% of the infused radioactivity was excreted into the urine within 5 h. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D2. Radiolabeled prostaglandin D2 urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. 25 metabolites were identified. 23 of these compounds comprising 37% of the recovered radioactivity had prostaglandin F-ring structures, and only two metabolites comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid which was isolated in a tricyclic form as a result of formation of a lower side chain hemiketal followed by lactonization of the terminal carboxyl and the hemiketal hydroxyl. Different isomeric forms of several prostaglandin F-ring metabolites were identified. An isomer of prostaglandin F2 alpha was also excreted intact into the urine as a metabolite of prostaglandin D2. 15 PGF-ring compounds were treated with n-butylboronic acid and 13 failed to form a boronate derivative, suggesting that the orientation of the hydroxyl group at C-11 in these 13 metabolites is beta. This study documents that prostaglandin D2 is metabolized to prostaglandin F-ring metabolites in vivo in humans. These results also bring into question the accuracy of quantifying prostaglandin F2 alpha metabolites as a specific index of endogenous prostaglandin F2 alpha biosynthesis, as well as quantifying urinary prostaglandin F2 alpha as an accurate index of renal production of prostaglandin F2 alpha.

• Research Organization: Vanderbilt Univ., Nashville, TN
• OSTI ID: 6085071
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 24; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CHROMATOGRAPHY
CLEARANCE
EXCRETION
GAS CHROMATOGRAPHY
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
MASS SPECTROSCOPY
MATERIALS
METABOLISM
METABOLITES
MOLECULAR STRUCTURE
PRIMATES
PROSTAGLANDINS
REACTION KINETICS
SEPARATION PROCESSES
SPECTROSCOPY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URINE
VERTEBRATES
WASTES