Stereoselective sulfation of terbutaline by the rat liver cytosol: Evaluation of experimental approaches

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Chirality (New York, N.Y.); (USA)

DOI:https://doi.org/10.1002/chir.530010205· OSTI ID:6511175

Walle, U K; Walle, T ^[1]

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1. Medical Univ. of South Carolina, Charleston (USA)

Little is known about the stereochemistry of sulfation of chiral phenolic drugs. In this study we examined several in vitro approaches to this question, using (+)-, (-)-, or (+/-)-terbutaline as the substrate and the rat liver cytosol as the phenolsulfotransferase enzyme source. The cosubstrate PAPS was either generated by the cytosol from inorganic sulfate and ATP or added to the cytosol. The intact sulfate conjugates formed were determined by HPLC. Using the PAPS generating system, which is best suited for the production of relatively large quantities of sulfate conjugates, with the individual enantiomers as substrates, (T)-terbutaline was conjugated to a much greater extent than (-)-terbutaline; the (+)/(-)-enantiomer ratio was 7.3 +/- 0.3 (mean +/- SE). When (+/-)-terbutaline was the substrate and chiral derivatization was employed to separate the sulfate enantiomers formed, a similar (+)/(-)-enantiomer ratio of 7.9 +/- 0.2 was obtained. With PAP35S added to the cytosol, an approach best suited for kinetic studies, the substrate concentration dependence of sulfation could be determined. The Km app for this reaction was identical for (+)- and (-)-terbutaline. However, the Vmax app was 8.1 +/- 0.4 times greater for (+)-terbutaline. This study for the first time shows enantioselectivity in sulfation of a chiral phenolic drug. The experimental approaches used should be valuable for human studies of stereoselective sulfation of terbutaline and other chiral drugs.

• OSTI ID: 6511175
• Journal Information: Chirality (New York, N.Y.); (USA), Journal Name: Chirality (New York, N.Y.); (USA) Vol. 1:2; ISSN 0899-0042; ISSN CHRLE
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARDIOVASCULAR AGENTS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
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LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLISM
NUCLEI
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ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
SEPARATION PROCESSES
STEREOCHEMISTRY
SULFUR 35
SULFUR ISOTOPES
TRACER TECHNIQUES
TRANSFERASES
VASODILATORS