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Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
The CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, 2A13, 2B6, and 2F1. The gene consists of nine exons (Rylander et al. 2001). The mRNA expression level of CYP2S1 is highest in trachea, lung, stomach, small intestine, and spleen (Deb and Bandiera 2009; Rylander et al. 2001; Saarikoski et al. 2005). There are also moderate expression of mRNA CYP2S1 in colon, appendix, liver, kidney, thymus, substantia nigra, peripheral leukocytes, and placenta. CYP2S1 metabolizes naphthalene, suggesting the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is involved in the synthesis and metabolism of bioactive lipids including PGs and retinoids (Bui et al. 2011; Fromel et al. 2013; Madanayake et al. 2012). CYP2S1 metabolizes PGG2 into several products including 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT). It also metabolizes PGH2 into malondialdehyde, 12-HHT, and thromboxane A2. CYP2S1 efficiently metabolizes the hydroperoxyeicosatetraenoic acids (5S-, 12S-, and 15S-HPETE) and 13S-hydroperoxyoctadecadienoic acid (HPODE) into 5-oxo-eicosatetraenoic acid (ETA), 12-oxo-ETA 1, 15-oxo-ETA, and 13-octadecadienoic acid, respectively (Bui et al. 2011). CYP2S1 can metabolize eicosanoids in the absence of both NADPH and NADPH cytochrome P450 reductase (Bui et al. 2011) and can also activate the anticancer agent AQ4N (banoxantrone, a highly selective bioreductive drug that is activated in, and is preferentially toxic to, hypoxic cells in tumors) (Nishida et al. 2010; Tan et al. 2011).
An inflammatory triangle in Sarcoidosis: PPAR-γ, immune microenvironment, and inflammation
Published in Expert Opinion on Biological Therapy, 2021
Parnia Jabbari, Mona Sadeghalvad, Nima Rezaei
PPARs belong to the nuclear hormone receptor superfamily consisting of 3 ligand-activated transcription factors including PPAR-α (known as NR1C3), PPAR-γ (known as NR1C1) and PPAR-δ (known as PPAR β or NR1C2). Each PPAR is encoded by diverse genes in different chromosomes, but their substantial amino acids and ligand-binding domains are similar to each other. PPAR-α and PPAR-γ, have the potential roles in inhibition of inflammatory-related genes expression [39,40]. A wide range of ligands may activate PPARs. For instance, long-chain fatty acids and eicosanoids are ligands for PPAR-α and PPAR-β/δ. By contrast, PPAR-γ is operated by arachidonic acid metabolites, like 5-oxo-15(S)-hydroxy eicosatetraenoic acid and 5-oxo-eicosatetraenoic acid [7].
Recent advances in the pharmacological management of constipation predominant irritable bowel syndrome
Published in Expert Opinion on Pharmacotherapy, 2020
Karolina Niewinna, Anna Zielińska, Jakub Fichna
Polyunsaturated fatty acids (PUFAs), bioactive lipids, are implicated in visceral hypersensitivity alternation: n-6 series PUFAs levels are high in patients suffering from chronic pain, including IBS patients [29]. 5-oxo-eicosatetraenoic acid (5-oxoETE) is a PUFA metabolite produced by various inflammatory cells. It derives from amino-acid metabolism and requires NADP+ for formation. IBS-C is associated with oxidative stress that stimulates the conversion rate of NADPH to NADP+ in epithelial cells and therefore larger amounts of 5-oxoETE are produced. In their study, Bautzova et al. quantified PUFA metabolites by mass spectrometry in colonic IBS biopsies. 5-oxoETE metabolite was significantly increased in IBS-C patients biopsies [30].