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Attributes of Peripheral Dopamine and Dopamine Receptors
Published in Nira Ben-Jonathan, Dopamine, 2020
The major metabolic inactivation of secreted peripheral DA in humans is sulfoconjugation. This reaction is carried out by the enzyme sulfotransferase type 1A3 (SULT1A3), which acts by transferring a sulfonate group (SO3−1) from a universal donor 3′-phospho-adenosine, 5′ phosphosulfate (PAP), to recipient molecules [22]. Sulfoconjugation is a rather common metabolic conversion, encompassing steroid and thyroid hormones, some neuroendocrine peptides, and glycoprotein hormones. Sulfoconjugation is known to alter the bioactivity, metabolic half-life, solubility, and/or receptor binding affinity of the affected hormones. Plasma DA is more than 95% sulfonated, and both the 3-O- and 4-O-sulfate isomers are present, with the 3-O-sulfate isomer being in a greater abundance by an order of magnitude [22].
Next-Generation Sequencing (NGS) for Companion Diagnostics (CDx) and Precision Medicine
Published in Il-Jin Kim, Companion Diagnostics (CDx) in Precision Medicine, 2019
Il-Jin Kim, Mendez Pedro, David Jablons
The first commercialized NGS system shown on the market was 454 pyrosequencing in 2005.3,24 For this system, dNTPs are added to the template-bound bead in a PicoTiterPlate.3 When each dNTP is incorporated into a newly synthesized DNA strand, a pyrophosphate molecule is produced and reacted with ATP sulfurylase, leading to a change of adenosine 5′ phosphosulfate (APS) into ATP.3 The covered ATP with luciferase changes luciferin into light and oxyluciferin. The generated light is detected by a charge-coupled device camera.3,18 Whereas 454 sequencing provides longer read lengths (i.e., 400–700 bp) than short read-length sequencing,18 higher error rates of indels in homopolymer regions are a main problem.18 Roche discontinued this system in 2016.
The Role of Steroid Sulfatase and Sulfotransferase Enzymes in the Metabolism of C21 and Cl9 Steroids
Published in Ronald Hobkirk, Steroid Biochemistry, 1979
The biosynthesis of steroid sulfates is brought about in two distinct reactions. The first is the formation of activated sulfate, 3’-phosphoadenosine-5’phosphosulfate (PAPS), in cytoplasm. This involves two separate steps, carried out by the enzymes sulfate adenylyl transferase (E.C. 2.7.7.4.) and adenylyl sulfate kinase (E.C. 2.7.1.25), which catalyze the formation of adenosine-5’-phosphosulfate (APS) and PAPS as shown below.
Microbiologically influenced corrosion on naval carbon steel inside the hull of tugboats: a case study of prevention and control
Published in Biofouling, 2023
Andrés Núñez, Ana M. García, Carlos Ranninger, Diego A. Moreno
The presence of marine anaerobic sulphate-reducing bacteria (SRB) was analysed in cultures prepared from 60 ml of water sample filtered through 0.22 μm filters (Merck Millipore Ltd., GSWP02500) and incubated in Postgate B culture medium supplemented with 3% sodium chloride (Postgate 1984) at 30 °C under anoxic conditions for 21 days. Tubes with black precipitate were marked positive for SRB presence. For DNA characterisation, 2 ml from these cultures were collected. The pellet was washed twice with 1 ml of sterile water and DNA was extracted as detailed above. 5 μl of the purified DNA were used as template for PCR. The DNA amplification of specific genes involved in SRB metabolism as the dissimilatory (bi)sulfite (dsrAB) and adenosine-5′-phosphosulfate reductases (apsA) has been proposed as an alternative to identify the presence of these bacteria by molecular approaches (Wagner et al. 2005; Anandkumar et al. 2016; Zarasvand and Rai 2016). Thus, primers DSV-F (5′-CTCGAGCGCTCCGGCGCCGT-3′) and DSV-R (5′-ACGAAGCGGTTTTCCATCATGGTC-3′) were designed to target the gene apsA of Desulfovibrio spp. As controls for the specificity of the primers, along with the samples from SRB cultures, DNA from Desulfovibrio sp. and Desulfomicrobium sp. were included in the PCR analyses, expecting a band of amplification for the former (positive control) and no amplification for the latter (negative control). The bands from positive amplifications were purified from the agarose gel and sequenced for bacterial assignation using Megablast.
Singularities of nevirapine metabolism: from sex-dependent differences to idiosyncratic toxicity
Published in Drug Metabolism Reviews, 2019
Aline T. Marinho, Joana P. Miranda, Umbelina Caixas, Catarina Charneira, Clara Gonçalves-Dias, M. Matilde Marques, Emília C. Monteiro, Alexandra M. M. Antunes, Sofia A. Pereira
In fact, SULT-mediated sulfonation is an essential process in Phase II biotransformation of several xenobiotics (Gamage et al. 2006; Marto et al. 2017). These reactions occur in the presence of the 3′-phosphoadenosine 5′-phosphosulfate (PAPS) cofactor, the donor of the SO3− group (Gamage et al. 2006; Suiko et al. 2017). The biosynthesis of PAPS comprises two sequential steps; the first one is performed by an ATP-sulfurylase, generating adenosine 5′-phosphosulfate (APS), and the following step involves APS phosphorylation by an APS kinase, resulting in the formation of PAPS (Venkatachalam et al. 1998; Coughtrie 2016). PAPS biosynthesis in man is catalyzed by PAPS synthase 1 and 2; both of the enzymes have ATP-sulfurylase and APS kinase activities (Venkatachalam et al. 1998; Fuda et al. 2002; Coughtrie 2016). PAPS synthase 2 presents significantly higher catalytic efficiency compared with PAPS synthase 1 (Fuda et al. 2002). PAPS has a female-predominant expression in liver in rodents (Alnouti and Klaassen 2006, 2011). It is also noteworthy that all hepatic SULTs with differential expression between sexes (e.g. SULT1A1, SULT1C2, SULT1D1, SULT2A1, SULT2A2, SULT3A1) are female-predominant in several animal models, such as rodents, canines, and swine, with the only exception of SULT1C1, which has higher hepatic expression in male mice and rats (Tsoi et al. 2001; Wu et al. 2001; Alnouti and Klaassen 2006, 2011; Hirao et al. 2011; Suzuki et al. 2012; Kojima and Degawa 2014; Chen et al. 2017). Although limited evidence has been generated for humans regarding sex differences on SULTs expression, it is important to highlight that both rodents (Herrmann et al. 2012; Tremmel et al. 2017) and swine (Puccinelli et al. 2011) have been considered translational animals models for the study of xenobiotics biotransformation. The sex differences in the expression of hepatic SULTs have been related to suppressive effects of androgens and stimulatory effects of estrogens, as well as with male and female patterns of growth hormone secretion (Alnouti and Klaassen 2011; Kojima and Degawa 2014). Importantly, one of the female-predominant SULTs, SULT1A1, can definitely promote in vitro sulfoconjugation of 12-OH-NVP (Figure 3; Sharma et al. 2013; Kranendonk et al. 2014). This specific SULT is expressed at high levels in human liver and skin, the target tissues for NVP toxicity (Dooley et al. 2000; Hempel et al. 2007). Furthermore, 12-OH-NVP is the predominant metabolite in plasma from NVP-treated women (Marinho et al. 2014b), which means higher substrate availability for SULT1A1 in females. Besides, another major NVP metabolite, 2-OH-NVP, is able to induce hepatic SULT1A1 activity, as demonstrated in a 3D model of rat hepatocytes (Pinheiro et al. 2017); therefore, 2-OH-NVP formation may further contribute to 12-OH-NVP bioactivation. Additionally, it has been reported that some CAR activators may upregulate the hepatic expression of several SULTs and PAPS synthase 2 in female mice, but not in males (Alnouti and Klaassen 2008). As previously mentioned, NVP is a CAR agonist (Faucette et al. 2006). Therefore, NVP exposure can exert differential effects according to sex, in terms of hepatic ability for sulfoconjugation.