Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system.

Human MRP4 (ABCC4, MOAT-B) is a lipophilic anion transporter that is able to confer resistance to nucleotide analogues and methotrexate (MTX). We previously investigated the implications of the ability of MRP4 to confer resistance to nucleotide analogues and determined that the pump is competent in the MgATP-energized transport of cyclic nucleotides and estradiol 17beta-D-glucuronide. Here we examine the potential role of MRP4 in conferring resistance to MTX and related processes by determining the selectivity of the transporter for MTX, MTX polyglutamates, and physiological folates.

Biochemical characterization and tissue distribution of human SULT2B1.

The human hydroxysteroid sulfotransferase (SULT) family is comprised of two subfamilies, SULT2A1 and SULT2B1. We characterized the substrate specificity, in vitro biochemical properties, and tissue distribution patterns of human SULT2B1a and SULT2B1b. In contrast to the wide substrate specificity of SULT2A1, SULT2B1a and SULT2B1b specifically catalyzed the sulfonation of 3beta-hydroxysteroids with high catalytic efficiency.

Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects.

Sulfotransferase (SULT) enzymes catalyze the sulfate conjugation of drugs, other xenobiotics, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in levels of enzyme activity as well as variations in biochemical and physical properties. We set out to compare the frequencies of common SULT1A1 and SULT1A2 alleles in Caucasian, Chinese and African-American subjects.

Estrogen metabolism by conjugation.

The involvement of estrogens in carcinogenic processes within estrogen-responsive tissues has been recognized for a number of years. Classically, mitogenicity associated with estrogen receptor-mediated cellular events was believed to be the mechanism by which estrogens contributed to carcinogenesis. Recently, the possibility that estrogens might contribute directly to mutagenesis resulting from DNA damage has been investigated.

Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization.

Sulfate conjugation catalyzed by sulfotransferase (SULT) enzymes is an important pathway in the biotransformation of many drugs, other xenobiotics, neurotransmitters, and hormones. We previously described a human cDNA, SULT1C1, that encoded a protein similar in sequence to that of rat ST1C1. Subsequently, a related human cDNA, SULT1C2, was reported.