Short-chain dehydrogenase/ reductases

Dihydroflavonol 4-reductase (DFR EC 1.1.1.219) is a member of the short-chain dehydrogenase/reductase family and catalyzes the stereospecific conversion of (+)-(2R,3R)-dihydroflavonols to the corresponding (2R,3S,4S) flavan-3,4-cw-diols (leucoanthocyanidins), with NADPH as a required cofactor. The enzyme activity was first identified in cell suspension cultures of Douglas fir (Pseudotsuga menziesii) and was shown to be related to the accumulation of flavan-3-ols and proanthocyanidins [96]. Leucoanthocyanidins and DFR were later shown to be required for anthocyanidin formation by complementation of Matthiola incana mutants blocked between dihydroflavonol and anthocyanidin biosynthesis [97, 98], DFR has been purified to apparent homogeneity and biochemically analyzed from flower buds of Dahlia variabilis [99]. DFR was shown to accept different substrates depending on the plant species from which it was isolated (reviewed in 100). 

DFR belongs to the single-domain-reductase/epimerase/dehydrogenase (RED) protein family, which has also been termed the short chain dehydrogenase/reductase (SDR) superfamily. This contains other flavonoid biosynthetic enzymes, in particular the anthocyanidin reductase (ANR), leucoanthocyanidin reductase (EAR), isoflavone reductase (IFR), and vestitone reductase (VR), as well as mammalian, bacterial, and other plant enzymes. ... 

H Jornvall, B Persson, M Krook, S Atrian, R Gonzalez-Duarte, J Jeffery, D Ghosh. Short-chain dehydrogenases/reductases (SDR). Biochemistry 34 6003-6013,1995. 

Abbreviations. ADH, alcohol dehydrogenase ALDH, aldehyde dehydrogenase AKR, aldo-keto reductases GST, glutathione -transferase MT, methyltransferase SDR, short-chain dehydrogenases/reductases SULT, sulfotransferase UGT, UDP-glucuronosyltransferase. 

Ziegler, J. Voegtlander, S., Schmidt, J., Kramell, R., Miersch, O., Ammer, C., Gesell, A. and Kutchan, T.M. (2006) Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. Plant.., 48,177-92. 

Dehydrogenase activity could clearly be separated from a ketosteroid iso-merase (see below) indicating that rDZ3 3-HSD is related to microbial HSDs of the short-chain dehydrogenase/reductase (SDR) family but not with mammalian HSDs, which are multifunctional enz)mies. 

Egerer-Sieber et al. (2006) reported on the purification and crystallization of recombinant 5p-POR from D. lanata. Later on, Gavidia et al. (2007) predicted that the 5p-POR belongs to the SDR family (Oppermann et al, 1997). Finally, Thorn et al. (2008) fully characterized the crystal structure and found that the progesterone reductase from D. lanata defines a novel class of short-chain dehydrogenases / reductases. 

Thorn, A., Egerer-Sieber, C., Jager, C.M., Herl, V., Muller-Uri, R, Kreis, W. and Muller, Y.A. (2008) The crystal structure of progesterone 5p-reductase from Digitalis lanata defines a novel class of short chain dehydrogenases/reductases. /. Biol. Chem., 283, 17260-9. 

Kavanagh, K. L., Jornvall, H., Persson, B., Oppermann, U. (2008). Medium- and short-chain dehydrogenase/reductase gene and protein families the SDR superfamily functional and structural diversity within a family of metabolic and regulatory enzymes. Cellular and Molecular Life Sciences, 65, 3895—3906. 

Short-chain dehydrogenases/ reductases Alcohol dehydrogenases... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

The synthesis and breakdown of fatty acids involves a cyclic series of reactions where the enzymes catalyzing these reactions fall into three major superfamilies the thiolase superfamily (synthases and thiolases), the short-chain dehydrogenase reductase superfamily (oxidoreductases), and the crotonase superfamily (hydra-tases and dehydratases). The enzymes comprising these three superfamilies include a significant portion of those found in microbial and mammalian metabolism. Many of the enzymes in microbial metabolism are potential drug targets. 

In discussions on the mechanisms of the enzymes involved in each pathway, there will be a particular focus on three superfamilies enzymes that share the thiolase fold and catalyze carbon—carbon bond formation and cleavage reactions catalyzed by NAD(P)-dependent enzymes in the fatty acid biosynthesis pathway involve proteins that are members of the short-chain dehydrogenase reductase (SDR) superfamily and finally there are mechanistic parallels between the hydration and dehydration reactions in each pathway with a particular focus on the crotonase superfamily. 

Oppermann, U.C., Filling, C., Bemdt, K.D., Persson, B., Benach, J., Ladenstein, R. Jornvall, H. (1997) Biochmistry 36, 34-40. Active site directed mutagenesis of 3 beta/17 beta-hydroxy-steroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions. 

JOrnvall, H., Persson, B., Krook, M., Atrian, S., Gonzalez-Duarte, R., Jeffery, J. Ghosh, D. (1995) Biochemistry, 34, 6003-6013, Short-chain dehydrogenases/reductases (SDR). 

Chen, X. and P. J. Facchini, Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy. Plant J., 2014. 77(2) p. 173-84. 

Cheng, W.H. Endo, A. Zhou, L. Penney, J. Chen, H.C. Arroyo, A. Leon, P. Nambara, E. Asami, T. Seo, M. Koshiba, T. Sheen, J. (2002). A unique short-chain dehydrogenase/reductase in Arabidopsis glucose signaling and abscisic acid biosynthesis and functions. Plant Cell, Vol.l4, No.ll, (November 2002), pp. 2723-2743, ISSN 1040-4651... 

SDR Short-chain dehydrogenase-reductase StAR Steroidogenic acute regulatoiy protein... 

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