# ARYL AND ALCOHOL SULFOTRANSFERASES IN DRUG METABOLISM

> **NIH NIH R01** · UNIVERSITY OF IOWA · 1993 · $134,938

## Abstract

The long-term goal of this research is to better understand the role that
aryl sulfotransferase (AST) IV and alcohol sulfotransferase STa play in
the  cytotoxic, immunologic, mutagenic, and carcinogenic responses to
drugs and other xenobiotics that either possess or are biotransformed
into metabolites containing arylhydroxamic acid, N-hydroxy arylamine, or
benzylic alcohol functional groups.  These functional groups are usually
encountered as intermediary metabolites of a multitude of different drugs
and other xenobiotics containing arylamine, nitroaromatic, and arylamide
functionalities as well as of xenobiotics possessing benzylic carbon
atoms that are susceptible to metabolic oxidation.  The research proposed
in this application is based on the premise that quantitative analyses of
the catalytic specificities and mechanisms of sulfotransferases and their
intratissue localizations and distributions are essential for accurately
predicting the potential for covalent alteration of macromolecules within
individual cells following exposure to xenobiotics that possess these
organic functional groups.  Investigations on the relationships between
AST IV and STa will focus on delineation of the degree of overlap in
their specificities for phenols, benzylic alcohols, N-hydroxy arylamines,
and arylhydroxamic acids as substrates and/ or inhibitors.  Quantitative
immunohistochemical methods will be used to determine overlap and/or
complementarity in the intratissue localizations and distributions of the
two enzymes in liver, skin, lung, and nasal mucosa of both male and
female rats.

In addition to these studies on the specificities and localizations of
these two sulfotransferases, investigations on the catalytic mechanism of
AST IV will be continued.  These studies will incorporate active
site-directed affinity labeling and peptide-sequencing in order to
elucidate the structures of peptides at the two major regions of the
active site (i.e., the PAPS-binding site and the binding site for a
sulfuryl acceptor).  Results from the affinity labeling experiments will
then guide collaborative studies on site-directed mutagenesis to provide
a more complete understanding of the catalytic mechanism of AST IV.

Thus, the multifaceted approach utilized in this project will result in a
significantly improved understanding of two of the major
sulfotransferases involved in the formation of sulfuric acid esters that
are implicated in the occurrence of chemical carcinogenesis and other
toxic responses following exposure to numerous xenobiotics.

## Key facts

- **NIH application ID:** 3176870
- **Project number:** 2R01CA038683-09A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **SAM.gov UEI:** Z1H9VJS8NG16
- **Principal Investigator:** MICHAEL W DUFFEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $134,938
- **Award type:** 2
- **Project period:** 1984-08-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176870

## Citation

> US National Institutes of Health, RePORTER application 3176870, ARYL AND ALCOHOL SULFOTRANSFERASES IN DRUG METABOLISM (2R01CA038683-09A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3176870. Licensed CC0.

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