Nomenclature and Molecular Biology of the Human Sulfotransferase Family

Blanchard, Rebecca

doi:10.1201/9781420024029.ch1

Cited by 2 publications

(2 citation statements)

References 131 publications

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“…There are five SULT1 subfamilies: SULT1A-E. SULT1A enzymes preferentially metabolize phenolic substrates, including drugs such as acetaminophen and troglitazone (Nagata and Yamazoe, 2000; Strott, 2002; Gamage et al, 2006; Runge-Morris and Kocarek, 2009). Humans express four SULT1A enzymes, including a high-affinity cate-cholamine-conjugating enzyme, SULT1A3/4, that is not present in rodents (Blanchard, 2005). Rodents express a single SULT1A enzyme that is most similar in activity to the human SULT1A1 phenol-sulfating enzyme (Falany et al, 1990; Duffel et al, 1991).…”

Section: The Sult Gene Superfamilymentioning

confidence: 99%

“…Several of these differences have been mentioned briefly above. As another major example, in contrast to humans, which have only one SULT2A family member, SULT2A1, rodents express multiple SULT2A transcripts (Blanchard, 2005). Analysis of the mouse genome indicates the presence of seven SULT2A genes clustered on chromosome 7 (Kocarek et al, 2008).…”

Section: Species Differences In Sult Expressionmentioning

confidence: 99%

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Regulation of the cytosolic sulfotransferases by nuclear receptors

Runge‐Morris

Kocarek

Falany

2013

Drug Metabolism Reviews

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The cytosolic sulfotransferases (SULTs) are a multigene family of enzymes that catalyze the transfer of a sulfonate group from the physiologic sulfate donor, 3′-phosphoadenosine-5′-phosphosulfate, to a nucleophilic substrate to generate a polar product that is more amenable to elimination from the body. As catalysts of both xenobiotic and endogenous metabolism, the SULTs are major points of contact between the external and physiological environments, and modulation of SULT-catalyzed metabolism can not only affect xenobiotic disposition, but it can also alter endogenous metabolic processes. Therefore, it is not surprising that SULT expression is regulated by numerous members of the nuclear receptor (NR) superfamily that function as sensors of xenobiotics as well as endogenous molecules, such as fatty acids, bile acids, and oxysterols. These NRs include the peroxisome proliferator-activated receptors, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, liver X receptors, farnesoid X receptor, retinoid-related orphan receptors, and estrogen-related receptors. This review summarizes current information about NR regulation of SULT expression. Because species differences in SULT subfamily composition and tissue-, sex-, development-, and inducer-dependent regulation are prominent, these differences will be emphasized throughout the review. In addition, because of the central role of the SULTs in cellular physiology, the effect of NR-mediated SULT regulation on physiological and pathophysiological processes will be discussed. Gaps in current knowledge that require further investigation are also highlighted.

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Section: The Sult Gene Superfamilymentioning

confidence: 99%

Section: Species Differences In Sult Expressionmentioning

confidence: 99%

Regulation of the cytosolic sulfotransferases by nuclear receptors

Runge‐Morris

Kocarek

Falany

2013

Drug Metabolism Reviews

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A high frequency missense SULT1B1 allelic variant (L145V) selectively expressed in African descendants exhibits altered kinetic properties

et al. 2017

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1. Human cytosolic sulfotransferase 1B1 (SULT1B1) sulfates small phenolic compounds and bioactivates polycyclic aromatic hydrocarbons. To date, no SULT1B1 allelic variants have been well-characterized. 2. While cloning SULT1B1 from human endometrial specimens, an allelic variant resulting in valine instead of leucine at the 145th amino acid position (L145V) was detected. NCBI reported this alteration as the highest frequency SULT1B1 allelic variant. 3. L145V frequency comprised 9% of 37 mixed-population human patients and was specific to African Americans with an allelic frequency of 25%. Structurally, replacement of leucine with valine potentially destabilizes a conserved helix (α8) that forms the "floor" of both the substrate and PAPS binding domains. This destabilization results in altered kinetic properties including a four-fold decrease in affinity for PAP (3', 5'-diphosphoadenosine). Ks for 3'-phosphoadenosine- 5'-phosphosulfate (PAPS) are similar; however, maximal turnover rate of the variant isoform (0.86 pmol/(min*μg)) is slower than wild-type (WT) SULT1B1 (1.26 pmol/(min*μg)). The L145V variant also displays altered kinetics toward small phenolic substrates, including a diminished p-nitrophenol K and increased susceptibility to 1-naphthol substrate inhibition. 4. No significant correlation between genotype and prostate or colorectal cancer was observed in patients; however, the variant isoform could underlie specific pathologies in sub-Saharan African carriers.

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Nomenclature and Molecular Biology of the Human Sulfotransferase Family

Cited by 2 publications

References 131 publications

Regulation of the cytosolic sulfotransferases by nuclear receptors

Regulation of the cytosolic sulfotransferases by nuclear receptors

A high frequency missense SULT1B1 allelic variant (L145V) selectively expressed in African descendants exhibits altered kinetic properties

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