PubMed Health⌕ Search

PubMed · 3042142

Phenol sulfotransferase inheritance.

Abstract

1. Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of many phenolic and catechol neurotransmitters. Human tissues contain both thermostable (TS) and thermolabile (TL) forms of PST that differ in their substrate specificities, inhibitor sensitivities, physical properties, and regulation. 2. Individual variations in the levels of activity of both TS and TL PST in the human platelet are strongly influenced by inheritance. 3. Individual differences in the level of platelet TS PST activity are correlated with individual variations in the activity of this form of the enzyme in human cerebral cortex, liver, and intestinal mucosa. 4. There are also individual familial differences in the thermal stability of TS PST in the platelet. These differences are correlated with individual variations in the thermal stability of TS PST in cerebral cortex, liver, and intestinal mucosa. 5. Individual variations in the thermal stability of TS PST in hepatic tissue are associated with the presence of one or both of a pair of TS PST isozymes that can be separated by ion-exchange chromatography and that differ in their thermal stabilities. 6. This series of observations suggests that a structural gene polymorphism may be one mechanism by which inheritance controls TS PST in humans. The isozymes of TS PST in liver may represent the products of alternative alleles for this polymorphism, alleles that might control the structure of TS PST in many human tissues.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R Weinshilboum. 1988. Phenol sulfotransferase inheritance.. https://doi.org/10.1007/bf00712908

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Generation and release of nitrotyrosine O-sulfate by HepG2 human hepatoma cells upon SIN-1 stimulation: identification of SULT1A3 as the enzyme responsible.

In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. Whether the body is equipped with mechanisms for protecting against the potentially harmful nitrotyrosine remains unknown. The present study was designed to investigate the possibility that sulfation serves as a pathway for the metabolism/regulation of nitrotyrosine. Using metabolic labelling, nitrotyrosine O-[35S]sulfate was found to be produced and released into the medium of HepG2 human hepatoma cells labelled with [35S]sulfate in the presence of nitrotyrosine. To identify the enzyme(s) responsible for nitrotyrosine sulfation, a systematic study of all eleven known human cytosolic SULTs (sulfotransferases) was performed. Of the 11 enzymes tested, only SULT1A3 displayed sulfating activity toward nitrotyrosine. The pH-dependence and kinetic constants of SULT1A3 with nitrotyrosine or dopamine as substrate were determined. To examine whether the sulfation of nitrotyrosine occurs in the context of cellular physiology, HepG2 cells labelled with [35S]sulfate were treated with SIN-1 (morpholinosydnonimine), a peroxynitrite generator. Increments of nitrotyrosine O-[35S]sulfate were detected in the medium of HepG2 cells treated with higher concentrations of SIN-1. To gain insight into the physiological relevance of nitrotyrosine sulfation, a time-course study was performed using [3H]tyrosine-labelled HepG2 cells treated with SIN-1. The findings confirm that the bulk of free [3H]nitrotyrosine inside the cells was present in the unconjugated form. The proportion of sulfated [3H]nitrotyrosine increased dramatically in the medium over time, implying that sulfation may play a significant role in the metabolism of free nitrotyrosine.

Arylsulfotransferase↗

Human cytosolic sulfotransferase SULT1A1.

Sulfonation is an important conjugation reaction required for a range of biological processes including phase II metabolism, whereby sulfo-conjugation renders a compound more hydrophilic to aid its excretion. The major enzyme responsible for xenobiotic sulfonation is the widely expressed cytosolic sulfotransferase SULT1A1. The SULT1A1 crystal structure has provided insights into this enzyme's substrate specificity and catalytic function, including its role in the sulfonation of endogenous substrates such as oestrogens. Contrary to its metabolic role, SULT1A1 can also bioactivate compounds; it is known to sulfonate pro-carcinogens such as hydroxymethyl polycyclic aromatic hydrocarbons leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis. Given the role of SULT1A1 in these diverse functions and the discovery of allelic variants with differing catalytic activities, this enzyme has been the focus of numerous polymorphic studies investigating the link between inter-individual SULT1A1 variance and the etiology of a variety of cancers.

Arylsulfotransferase↗

Epigenetic silencing of the sulfotransferase 1A1 gene by hypermethylation in breast tissue.

Sulfotransferase 1A1 (SULT1A1) is reported to be involved in the conjugation with sulfate, resulting in the inactivation of estrogens. Aberrant methylation of promoter CpG islands is known to be responsible for the alteration and silencing of the gene in cancers. This study was intended to evaluate the methylation status and transcriptional activity of SULT1A1 in breast cancer tissue (n=56), benign breast tissue (n=20) and morphologically normal breast tissue (n=20), examined by bisulfite genomic sequencing and reverse transcription (RT)-PCR. As a result, the methylation of the proximal promoter (P1) was identified in 64.3% of breast carcinomas, 15% of normal and 20% of benign breast tissues. In terms of the distal promoter (P0), 32 of 56 cancer tissues (57.1%) were methylated, while 4 normal (20%) and 6 benign tissues (30%) were methylated. Breast cancer tissue showed a higher methylation rate of SULT1A1 than normal and benign tissue at both P1 (p=0.001) and P0 (p=0.006) promoters with statistical significance. Furthermore, cancer tissue showed a higher methylation density rate than normal and benign breast tissue at both P1 and P0 promoters (P1, p=0.001; P0, p=0.001). The tissues that showed aberrant methylation of SULT1A1 did not express mRNA significantly, compared with the unmethylated cases (P1, p=0.003; P0, p=0.023). Although the number of samples was relatively small, our results suggest that DNA methylation in the SULT1A1 gene appears to be present in breast tissue including cancer and methylation significantly impacts transcriptional silencing of the gene. In addition, it can be suggested that progressive SULT1A1 methylation within the promoter area of the gene occurs during breast carcinogenesis.

Arylsulfotransferase↗