Formation of thiol conjugates of 9-deoxy-. Delta. sup 9 ,. Delta. sup 12 (E)-prostaglandin D sub 2 and. Delta. sup 12 (E)-prostaglandin D sub 2

Journal Article · Tue Apr 10 04:00:00 EDT 1990 · Biochemistry; (USA)

OSTI ID:6323235

Atsom, J; Sweetman, B J; Baertschi, S W; Harris, T M; Roberts, II, L J ^[1]

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1. Vanderbilt Univ., Nashville, TN (USA)

Albumin catalyzes the transformation of prostaglandin D{sub 2} to 9-deoxy-{Delta}{sup 9}, {Delta}{sup 12}(E)-prostaglandin D{sub 2} and to isomeric prostaglandin D{sub 2} compounds including {Delta}{sup 12}(E)-prostaglandin D{sub 2}. Both of these compounds are {alpha},{beta}-unsaturated ketones, which should render them susceptible to nucleophilic addition. The authors therefore examined the ability of the compounds to form conjugates with thiols glutathione and cysteine. During incubation with excess glutathione, both 9-deoxy-{Delta}{sup 9},{Delta}{sup 12}(E)-prostaglandin D{sub 2} and {Delta}{sup 12}(E)-prostaglandin D{sub 2} formed a conjugate. The formation of both conjugates was enhanced by glutathione S-transferase. Conjugation of both compounds with cysteine was found to occur more rapidly than with glutathione. Analysis by fast atom bombardment mass spectrometry confirmed the formation of the glutathione conjugate of 9-deoxy-{Delta}{sup 9},{Delta}{sup 12}(E)-prostaglandin D{sub 2}. {sup 1}H NMR analysis determined that in the mono glutathione conjugate of 9-deoxy-{Delta}{sup 9},{Delta}{sup 12}(E)-prostaglandin D{sub 2} the glutathione was conjugated at C-9. To assess the formation of conjugates in vivo, tritiated 9-deoxy-{Delta}{sup 9},{Delta}{sup 12}(E)-prostaglandin D{sub 2} was injected intravenously in a rat, and urine and bile were collected for 4 h. Of the recovered radioactivity, 90% was excreted into the bile. Essentially all of the radioactivity in the bile was present in the form of a polar conjugate. HPLC analysis of the bile revealed a major radioactive peak with an elution volume characteristic for the of the glutathione conjugate of 9-deoxy-{Delta}{sup 9},{Delta}{sup 12}(E)-prostaglandin D{sub 2} suggesting that conjugation of this prostaglandin with glutathione may also occur in vivo.

• OSTI ID: 6323235
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:14; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ALBUMINS
ANIMALS
BIOCHEMISTRY
BLOOD SERUM
CHEMISTRY
CHROMATOGRAPHY
DRUGS
ENZYMES
GLUTATHIONE
HYDROGEN COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAGNETIC RESONANCE
MAMMALS
MAN
NUCLEAR MAGNETIC RESONANCE
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
PRIMATES
PROSTAGLANDINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESONANCE
SEPARATION PROCESSES
THIOLS
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES