Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3)

Lundová, Tereza; Zemanová, Lucie; Malčeková, B.; Skarka, Adam; Štambergová, Hana; Havránková, Jana; Šafr, Miroslav; Wsól, Vladimı́r

doi:10.1016/j.cbi.2014.10.018

Cited by 13 publications

(9 citation statements)

References 47 publications

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“…In the brain, DHRS3 also localizes to the developing pituitary, cerebellum, and choroid plexus and has been observed in the retina, thyroid, lung, and intestine (Figure ) . In addition to mouse embryos, DHRS3 is known to be active in human testes, liver, and small intestine tissues …”

Section: Molecular Determinants Of Retinoid Metabolism In Embryonic Tmentioning

confidence: 97%

“…Recently, we and others described a role for the short‐chain dehydrogenase/reductase (SDR) family, member 3 (DHRS3) in reducing retinaldehyde to retinol . Dhrs3 is expressed in a dynamic spatiotemporal pattern that overlaps with many tissues in which vitamin A metabolism and signaling are known to occur during mouse embryogenesis.…”

Section: Molecular Determinants Of Retinoid Metabolism In Embryonic Tmentioning

confidence: 99%

“…Recently, we and others described a role for the short-chain dehydrogenase/reductase (SDR) family, member 3 (DHRS3) in reducing retinaldehyde to retinol. 135,139,141,157,158 Dhrs3 is expressed in a dynamic spatiotemporal pattern that overlaps with many tissues in which vitamin A metabolism and signaling are known to occur during mouse embryogenesis. The highest levels of DHRS3 protein in E14.5 embryos are observed in the liver, kidney, nasal epithelium, and interdigital zones of limbs ( Figure 2).…”

Section: Interconversion Of Retinol and Retinaldehydementioning

confidence: 99%

“…135 In addition to mouse embryos, DHRS3 is known to be active in human testes, liver, and small intestine tissues. 157 Loss-of-function studies in mice have demonstrated that Dhrs3 −/− is critical for normal embryogenesis as mutant embryos dye during late gestation, around E17.5 to E18.5. 135 Similar to models of Rdh10 loss-of-function, Dhrs3 −/− mutant embryos display perturbed craniofacial, heart, and axial development ( Figure 2 and Table 1).…”

Section: Interconversion Of Retinol and Retinaldehydementioning

confidence: 99%

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New insights and changing paradigms in the regulation of vitamin A metabolism in development

Shannon

Moise

Trainor

2017

WIREs Developmental Biology

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Vitamin A and its active metabolite retinoic acid are essential for embryonic development and adult homeostasis. Surprisingly, excess or deficiency of vitamin A and retinoic acid can cause similar developmental defects. Therefore, strict feedback and other mechanisms exist to regulate the levels of retinoic acid within a narrow physiological range. The oxidation of vitamin A to retinal has recently been established as a critical nodal point in the synthesis of retinoic acid, and over the past decade, RDH10 and DHRS3 have emerged as the predominant enzymes that regulate this reversible reaction. Together they form a codependent complex that facilitates negative feedback maintenance of retinoic acid levels and thus guard against the effects of dysregulated vitamin A metabolism and retinoic acid synthesis. This review focuses on advances in our understanding of the roles of Rdh10 and Dhrs3 and their impact on development and disease.

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Section: Molecular Determinants Of Retinoid Metabolism In Embryonic Tmentioning

confidence: 97%

Section: Molecular Determinants Of Retinoid Metabolism In Embryonic Tmentioning

confidence: 99%

Section: Interconversion Of Retinol and Retinaldehydementioning

confidence: 99%

Section: Interconversion Of Retinol and Retinaldehydementioning

confidence: 99%

See 2 more Smart Citations

New insights and changing paradigms in the regulation of vitamin A metabolism in development

Shannon

Moise

Trainor

2017

WIREs Developmental Biology

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“…Human DHRS3 shares 54% sequence identity with human RDH10 at the amino acid level. Both are integral membrane proteins [115,116,138]. Importantly, the enzymes reciprocally activate each other when the two proteins are present together on the same membrane [135].…”

Section: Reciprocal Interconversion Of Rol and Ral By Membrane-boumentioning

confidence: 99%

Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos

Metzler

Sandell

2016

Nutrients

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Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for vertebrate embryonic development because it is the molecular precursor of the essential signaling molecule RA. The level and distribution of RA signaling within a developing embryo must be tightly regulated; too much, or too little, or abnormal distribution, all disrupt embryonic development. Precise regulation of RA signaling during embryogenesis is achieved by proteins involved in vitamin A metabolism, retinoid transport, nuclear signaling, and RA catabolism. The reversible first step in conversion of the precursor vitamin A to the active retinoid RA is mediated by retinol dehydrogenase 10 (RDH10) and dehydrogenase/reductase (SDR family) member 3 (DHRS3), two related membrane-bound proteins that functionally activate each other to mediate the interconversion of retinol and retinal. Alcohol dehydrogenase (ADH) enzymes do not contribute to RA production under normal conditions during embryogenesis. Genes involved in vitamin A metabolism and RA catabolism are expressed in tissue-specific patterns and are subject to feedback regulation. Mutations in genes encoding these proteins disrupt morphogenesis of many systems in a developing embryo. Together these observations demonstrate the importance of vitamin A metabolism in regulating RA signaling during embryonic development in vertebrates.

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Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties

et al. 2015

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Dehydrogenase/reductase (SDR family) member 8 (DHRS8, SDR16C2) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, one of the largest enzyme groups. In addition to the well-known members which participate in the metabolism of important eobiotics and xenobiotics, this superfamily contains many poorly characterized proteins. DHRS8 is a member of the Multisubstrate NADP(H)-dependent SDR16C family, which generally contains insufficiently described enzymes. Despite the limited knowledge about DHRS8, preliminary indicators have emerged regarding its significant function in the modulation of steroidal activity, at least in the case of 3α-adiol, lipid metabolism and detoxification. The aim of this study was to describe additional biochemical properties of DHRS8 and to unify knowledge about this enzyme. The DHRS8 was prepared in recombinant form and its membrane topology in the endoplasmic reticulum as an integral protein with cytosolic orientation was demonstrated. The enzyme participates in the NAD(+)-dependent oxidation of steroid hormones as β-estradiol and testosterone in vitro; apparent K m and V max values were 39.86 µM and 0.80 nmol × mg(-1) × min(-1) for β-estradiol and 1207.29 µM and 3.45 nmol × mg(-1) × min(-1) for testosterone. Moreover, synthetic steroids (methyltestosterone and nandrolone) used as anabolics as well as all-trans-retinol were for the first time identified as substrates of DHRS8. This knowledge of its in vitro activity together with a newly described expression pattern at the protein level in tissues involved in steroidogenesis (adrenal gland and testis) and detoxification (liver, lung, kidney and small intestine) could suggest a potential role of DHRS8 in vivo.

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Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3)

Cited by 13 publications

References 47 publications

New insights and changing paradigms in the regulation of vitamin A metabolism in development

New insights and changing paradigms in the regulation of vitamin A metabolism in development

Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos

Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties

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