oxidoreductases acting on ch ch group donors


Summary: A subclass of enzymes which includes all dehydrogenases acting on carbon-carbon bonds. This enzyme group includes all the enzymes that introduce double bonds into substrates by direct dehydrogenation of carbon-carbon single bonds.

Top Publications

  1. Bennati A, Schiavoni G, Franken S, Piobbico D, Della Fazia M, Caruso D, et al. Disruption of the gene encoding 3beta-hydroxysterol Delta-reductase (Tm7sf2) in mice does not impair cholesterol biosynthesis. FEBS J. 2008;275:5034-47 pubmed publisher
    ..Affymetrix microarray analysis of gene expression revealed that several genes involved in cell-cycle progression are downregulated in the liver of Tm7sf2((-/-)) mice, whereas genes involved in xenobiotic metabolism are upregulated. ..
  2. Wassif C, Krakowiak P, Wright B, Gewandter J, Sterner A, Javitt N, et al. Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. Mol Genet Metab. 2005;85:96-107 pubmed
  3. Matsumoto Y, Morishima K, Honda A, Watabe S, Yamamoto M, Hara M, et al. R352Q mutation of the DHCR7 gene is common among Japanese Smith-Lemli-Opitz syndrome patients. J Hum Genet. 2005;50:353-6 pubmed
    ..These results suggest that R352Q is a predominant founder mutation in Japanese SLOS patients. ..
  4. Yu H, Patel S. Recent insights into the Smith-Lemli-Opitz syndrome. Clin Genet. 2005;68:383-91 pubmed
    ..This mini review summarizes the recent insights into SLOS genetics, pathophysiology and potential therapeutic approaches for the treatment of SLOS. ..
  5. Tulenko T, Boeze Battaglia K, Mason R, Tint G, Steiner R, Connor W, et al. A membrane defect in the pathogenesis of the Smith-Lemli-Opitz syndrome. J Lipid Res. 2006;47:134-43 pubmed
    ..These data indicate that the disturbance in membrane sterol content in SLOS, likely at the level of membrane caveolae, directly contributes to the widespread tissue abnormalities in this disease. ..
  6. Bennati A, Castelli M, Della Fazia M, Beccari T, Caruso D, Servillo G, et al. Sterol dependent regulation of human TM7SF2 gene expression: role of the encoded 3beta-hydroxysterol Delta14-reductase in human cholesterol biosynthesis. Biochim Biophys Acta. 2006;1761:677-85 pubmed
    ..The results suggest a primary role of C14SR in human cholesterol biosynthesis, whereas LBR role in the pathway remains unclear. ..
  7. Breithaupt C, Kurzbauer R, Lilie H, Schaller A, Strassner J, Huber R, et al. Crystal structure of 12-oxophytodienoate reductase 3 from tomato: self-inhibition by dimerization. Proc Natl Acad Sci U S A. 2006;103:14337-42 pubmed publisher
    ..This mechanism could contribute to the shaping of the oxylipin signature, which is critical for fine-tuning gene expression in plants...
  8. Chen Z, Pudas R, Sharma S, Smart O, Juffer A, Hiltunen J, et al. Structural enzymological studies of 2-enoyl thioester reductase of the human mitochondrial FAS II pathway: new insights into its substrate recognition properties. J Mol Biol. 2008;379:830-44 pubmed publisher
    ..Furthermore, the kinetic analysis of the wild-type MECR/ETR1 shows a bimodal distribution of catalytic efficiencies, in agreement with the notion that two major products are generated by the mitochondrial FAS II pathway. ..
  9. Zeng R, Yao Y, Han M, Zhao X, Liu X, Wei J, et al. Biliverdin reductase mediates hypoxia-induced EMT via PI3-kinase and Akt. J Am Soc Nephrol. 2008;19:380-7 pubmed publisher
    ..In conclusion, biliverdin reductase mediates hypoxia-induced EMT through a PI3K/Akt-dependent pathway. ..

More Information


  1. Fox B, Malone T, Johnson K, Madson S, Aceti D, Bingman C, et al. X-ray structure of Arabidopsis At1g77680, 12-oxophytodienoate reductase isoform 1. Proteins. 2005;61:206-8 pubmed
  2. GONDRE LEWIS M, Petrache H, Wassif C, Harries D, Parsegian A, Porter F, et al. Abnormal sterols in cholesterol-deficiency diseases cause secretory granule malformation and decreased membrane curvature. J Cell Sci. 2006;119:1876-85 pubmed
  3. Crameri A, Biondi E, Kuehnle K, Lutjohann D, Thelen K, Perga S, et al. The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. EMBO J. 2006;25:432-43 pubmed
    ..Pharmacological enhancement of seladin-1 activity may be a novel Abeta-lowering approach for the treatment of AD. ..
  4. Fuller P, Alexiadis M, Jobling T, McNeilage J. Seladin-1/DHCR24 expression in normal ovary, ovarian epithelial and granulosa tumours. Clin Endocrinol (Oxf). 2005;63:111-5 pubmed
    ..Based on our results, seladin-1 is not expressed in the granulosa cells or at least not in those that give rise to GCT. ..
  5. Battista M, Roberge C, Otis M, Gallo Payet N. Seladin-1 expression in rat adrenal gland: effect of adrenocorticotropic hormone treatment. J Endocrinol. 2007;192:53-66 pubmed
    ..Results also suggest that depending on its cellular localization, the Delta24-reductase activity of Seladin-1 may play a major role in steroid secretion in the adrenal gland. ..
  6. Jong Hee Chae -, Ki Joong Kim -, Yong Seung Hwang -, Ki C, Kim J. Identification of a novel DHCR7 mutation in a Korean patient with Smith-Lemli-Opitz syndrome. J Child Neurol. 2007;22:1297-300 pubmed
    ..The Lys376ArgfsX37 mutation is a novel mutation, and to the best of the authors' knowledge, this is the first report of a clinically and genetically confirmed case of Smith-Lemli-Opitz syndrome in Korea. ..
  7. Porter F. Smith-Lemli-Opitz syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2008;16:535-41 pubmed publisher
    ..This review discusses the clinical aspects and diagnosis of SLOS, therapeutic interventions and the current understanding of pathophysiological processes involved in SLOS. ..
  8. Zhang J, Simmons C, Yalpani N, Crane V, Wilkinson H, Kolomiets M. Genomic analysis of the 12-oxo-phytodienoic acid reductase gene family of Zea mays. Plant Mol Biol. 2005;59:323-43 pubmed
    ..None of the treatments induced transcripts of ZmOPR3, 4, or 5. ..
  9. Wang X, He X, Lin J, Shao H, Chang Z, Dixon R. Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.). J Mol Biol. 2006;358:1341-52 pubmed
    ..This study provides a structural basis for understanding the enzymatic mechanism and substrate specificity of IFRs as well as the functions of IFR-like proteins. ..
  10. Lu X, Kambe F, Cao X, Kozaki Y, Kaji T, Ishii T, et al. 3beta-Hydroxysteroid-delta24 reductase is a hydrogen peroxide scavenger, protecting cells from oxidative stress-induced apoptosis. Endocrinology. 2008;149:3267-73 pubmed publisher
    ..These results demonstrate that DHCR24 can directly scavenge H(2)O(2), thereby protecting cells from oxidative stress-induced apoptosis. ..
  11. Hiltunen J, Okubo F, Kursu V, Autio K, Kastaniotis A. Mitochondrial fatty acid synthesis and maintenance of respiratory competent mitochondria in yeast. Biochem Soc Trans. 2005;33:1162-5 pubmed
    ..Finally, Hfa1p was shown to be the mitochondrial acetyl-CoA carboxylase. ..
  12. Kuehnle K, Crameri A, Kälin R, Luciani P, Benvenuti S, Peri A, et al. Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Mol Cell Biol. 2008;28:539-50 pubmed
    ..Our findings reveal a dual capacity of DHCR24/seladin-1, which appears to be involved in two mechanistically independent prosurvival effects, exerting an acute response and a chronic response to oxidative stress. ..
  13. Shao H, Dixon R, Wang X. Crystal structure of vestitone reductase from alfalfa (Medicago sativa L.). J Mol Biol. 2007;369:265-76 pubmed
    ..A molecular docking study showed that (3R)-vestitone, but not the (3S) isomer, forms favored interactions with the co-factor and catalytic triad, thus providing an explanation for the enzyme's strict substrate stereo-specificity. ..
  14. Heverin M, Meaney S, Brafman A, Shafir M, Olin M, Shafaati M, et al. Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler Thromb Vasc Biol. 2007;27:2191-7 pubmed
    ..Characterization of cholesterol homeostasis in male mice with a genetic inactivation of 3beta-hydroxysteroid-delta24-reductase, causing replacement of almost all cholesterol with desmosterol...
  15. Kovarova M, Wassif C, Odom S, Liao K, Porter F, Rivera J. Cholesterol deficiency in a mouse model of Smith-Lemli-Opitz syndrome reveals increased mast cell responsiveness. J Exp Med. 2006;203:1161-71 pubmed
    ..These findings provide the first evidence of lipid raft dysfunction in SLOS and may explain the observed association of allergy with SLOS. ..
  16. Chen Z, Leskinen H, Liimatta E, Sormunen R, Miinalainen I, Hassinen I, et al. Myocardial overexpression of Mecr, a gene of mitochondrial FAS II leads to cardiac dysfunction in mouse. PLoS ONE. 2009;4:e5589 pubmed publisher
    ..Furthermore, the data suggested that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy. ..
  17. Tani T, Sobajima H, Okada K, Chujo T, Arimura S, Tsutsumi N, et al. Identification of the OsOPR7 gene encoding 12-oxophytodienoate reductase involved in the biosynthesis of jasmonic acid in rice. Planta. 2008;227:517-26 pubmed
    ..We conclude that the OsOPR7 gene encodes the enzyme catalysing the reduction of natural (+)-cis-OPDA for the JA biosynthesis in rice. ..
  18. Witsch Baumgartner M, Clayton P, Clusellas N, Haas D, Kelley R, Krajewska Walasek M, et al. Identification of 14 novel mutations in DHCR7 causing the Smith-Lemli-Opitz syndrome and delineation of the DHCR7 mutational spectra in Spain and Italy. Hum Mutat. 2005;25:412 pubmed
    ..Thr93Met on the J haplotype as the most frequent Mediterranean founder mutation. ..
  19. Yu H, Wessels A, Tint G, Patel S. Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression. Brain Res Dev Brain Res. 2005;156:46-60 pubmed
    ..Another conclusion is that even small and subtle changes in the brain sterol metabolism were sufficient to enable rescue. These data also provide important clues as to the cause of the variable expressivity seen in SLOS. ..
  20. Pachori A, Smith A, McDonald P, Zhang L, Dzau V, Melo L. Heme-oxygenase-1-induced protection against hypoxia/reoxygenation is dependent on biliverdin reductase and its interaction with PI3K/Akt pathway. J Mol Cell Cardiol. 2007;43:580-92 pubmed
    ..This effect is mediated, at least in part, via interaction with and activation of the PI3K/Akt pathway. ..
  21. Yu W, Chu X, Chen G, Li D. Studies of human mitochondrial 2,4-dienoyl-CoA reductase. Arch Biochem Biophys. 2005;434:195-200 pubmed
    ..Another analog, 3-furan-2-yl-acrylyl-CoA, was not a substrate, but a competitive inhibitor of the enzyme. These studies increased our understanding of human mitochondrial 2,4-dienoyl-CoA reductase. ..
  22. Turner J, Ellis C, Devoto A. The jasmonate signal pathway. Plant Cell. 2002;14 Suppl:S153-64 pubmed
  23. Krakowiak P, Wassif C, Kratz L, Cozma D, Kovarova M, Harris G, et al. Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet. 2003;12:1631-41 pubmed
    ..We identified a homozygous mutation of SC5D (137A>C, Y46S) in this patient. An unique aspect of the lathosterolosis phenotype is the combination of a malformation syndrome with an intracellular storage defect. ..
  24. Min T, Kasahara H, Bedgar D, Youn B, Lawrence P, Gang D, et al. Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases. J Biol Chem. 2003;278:50714-23 pubmed
    ..The basis for the distinct enantio-specific and regio-specific reactions of PCBER, PLR, and IFR, as well as the reaction mechanism and participating residues involved (as identified by site-directed mutagenesis), are discussed. ..
  25. Iivonen S, Hiltunen M, Alafuzoff I, Mannermaa A, Kerokoski P, Puolivali J, et al. Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease. Neuroscience. 2002;113:301-10 pubmed
    ..The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer's disease and this down-regulation is associated with the hyperphosphorylation of tau protein. ..
  26. Sobajima H, Takeda M, Sugimori M, Kobashi N, Kiribuchi K, Cho E, et al. Cloning and characterization of a jasmonic acid-responsive gene encoding 12-oxophytodienoic acid reductase in suspension-cultured rice cells. Planta. 2003;216:692-8 pubmed
    ..Thus the rice enzyme was termed OsOPR1. The physiological roles of OsOPR1 are discussed. This is the first report of the cloning of an OPR gene from a monocot plant. ..
  27. Alphey M, Yu W, Byres E, Li D, Hunter W. Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site. J Biol Chem. 2005;280:3068-77 pubmed
    ..Key to the acquisition of a solvent-derived proton is the orientation of substrate and stabilization of a dienolate intermediate by Tyr-199, Asn-148, and the oxidized nicotinamide. ..
  28. Andersson H, Kratz L, Kelley R. Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay. Am J Med Genet. 2002;113:315-9 pubmed
    ..This unique patient broadens the spectrum of inborn errors of cholesterol biosynthesis and suggests additional candidate clinical phenotypes associated with abnormal cholesterol metabolism. ..
  29. Strassner J, Schaller F, Frick U, Howe G, Weiler E, Amrhein N, et al. Characterization and cDNA-microarray expression analysis of 12-oxophytodienoate reductases reveals differential roles for octadecanoid biosynthesis in the local versus the systemic wound response. Plant J. 2002;32:585-601 pubmed
    ..The transcriptional activation of the octadecanoid pathway and the accumulation of JA to high levels are, thus not required for the activation of defense gene expression in systemic tissues. ..
  30. Miinalainen I, Chen Z, Torkko J, Pirilä P, Sormunen R, Bergmann U, et al. Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II. J Biol Chem. 2003;278:20154-61 pubmed
  31. Brunetti Pierri N, Corso G, Rossi M, Ferrari P, Balli F, Rivasi F, et al. Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. Am J Hum Genet. 2002;71:952-8 pubmed
    ..Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis. ..
  32. Wechsler A, Brafman A, Shafir M, Heverin M, Gottlieb H, Damari G, et al. Generation of viable cholesterol-free mice. Science. 2003;302:2087 pubmed
  33. Matsui H, Nakamura G, Ishiga Y, Toshima H, Inagaki Y, Toyoda K, et al. Structure and expression of 12-oxophytodienoate reductase (subgroup I) genes in pea, and characterization of the oxidoreductase activities of their recombinant products. Mol Genet Genomics. 2004;271:1-10 pubmed
  34. Yu H, Wessels A, Chen J, Phelps A, Oatis J, Tint G, et al. Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev Biol. 2004;4:1 pubmed
    ..The molecular mechanism of impaired lung development associated with sterol deficiency by Dhcr7 loss is still unknown, but these results do not support the involvement of dysregulated Shh-Patched-Gli pathway in causing this defect. ..
  35. Malone T, Madson S, Wrobel R, Jeon W, Rosenberg N, Johnson K, et al. X-ray structure of Arabidopsis At2g06050, 12-oxophytodienoate reductase isoform 3. Proteins. 2005;58:243-5 pubmed
  36. Wu C, Miloslavskaya I, Demontis S, Maestro R, Galaktionov K. Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature. 2004;432:640-5 pubmed
    ..These results show an unanticipated role for Seladin-1, previously implicated in Alzheimer's disease and cholesterol metabolism, in integrating cellular response to oncogenic and oxidative stress. ..
  37. Refolo L, Pappolla M, LaFrancois J, Malester B, Schmidt S, Thomas Bryant T, et al. A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2001;8:890-9 pubmed
    ..This study demonstrates that hypocholesterolemia is associated with reduced Abeta accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reducing the risk of developing AD. ..
  38. Fitzky B, Moebius F, Asaoka H, Waage Baudet H, Xu L, Xu G, et al. 7-Dehydrocholesterol-dependent proteolysis of HMG-CoA reductase suppresses sterol biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH syndrome. J Clin Invest. 2001;108:905-15 pubmed
    ..This effect might exacerbate abnormal development in SLOS by increasing the fetal cholesterol deficiency. ..
  39. Chu X, Yu W, Chen G, Li D. Expression, purification, and characterization of His-tagged human mitochondrial 2,4-dienoyl-CoA reductase. Protein Expr Purif. 2003;31:292-7 pubmed
  40. Rossi M, Vajro P, Iorio R, Battagliese A, Brunetti Pierri N, Corso G, et al. Characterization of liver involvement in defects of cholesterol biosynthesis: long-term follow-up and review. Am J Med Genet A. 2005;132A:144-51 pubmed
    ..Periodic liver function evaluations are recommended in these patients. ..
  41. Manolagas S. De-fense! De-fense! De-fense: scavenging H2O2 while making cholesterol. Endocrinology. 2008;149:3264-6 pubmed publisher
  42. Zhang S, Sakuradani E, Shimizu S. Identification of a sterol Delta7 reductase gene involved in desmosterol biosynthesis in Mortierella alpina 1S-4. Appl Environ Microbiol. 2007;73:1736-41 pubmed
    ..This indicates that MoDelta7SR is involved in desmosterol biosynthesis in M. alpina 1S-4. This study is the first report on characterization of sterol Delta7 reductase from a microorganism. ..
  43. Ding B, Schmeling S, Fuchs G. Anaerobic metabolism of catechol by the denitrifying bacterium Thauera aromatica--a result of promiscuous enzymes and regulators?. J Bacteriol. 2008;190:1620-30 pubmed
    ..Hence, the promiscuity of several enzymes and regulatory proteins may be sufficient to create the catechol pathway that is made up of elements of phenol, 3-hydroxybenzoate, 4-hydroxybenzoate, and benzoate metabolism...
  44. Shimamura H, Sunazuka T, Izuhara T, Hirose T, Shiomi K, Omura S. Total synthesis and biological evaluation of verticipyrone and analogues. Org Lett. 2007;9:65-7 pubmed
    ..During total synthetic studies, we also prepared and evaluated several synthetic verticipyrone analogues, some of which exhibited more potent antiparasitic activity than the natural verticipyrone. ..
  45. Sakasegawa S, Ishikawa H, Imamura S, Sakuraba H, Goda S, Ohshima T. Bilirubin oxidase activity of Bacillus subtilis CotA. Appl Environ Microbiol. 2006;72:972-5 pubmed
    ..This is the first characterization of bilirubin oxidase activity in a bacterial protein. ..
  46. Oslejskova H, Horinova V, Sterba J, Pavelka Z, Babovic Vuksanovic D, Dubska L, et al. Malignant intracranial germinoma in Smith-Lemli-Opitz syndrome: cholesterol homeostasis possibly connecting morphogenesis and cancer development. J Pediatr Hematol Oncol. 2008;30:689-91 pubmed publisher
    ..Here, we describe a 16-year-old boy with Smith-Lemli-Opitz syndrome who developed cerebral germinoma. To our knowledge, this is the first report of association of this syndrome with malignant intracranial germ-cell tumor. ..
  47. Li X, Nicholl D. Development of PPO inhibitor-resistant cultures and crops. Pest Manag Sci. 2005;61:277-85 pubmed
  48. Peri A, Danza G, Benvenuti S, Luciani P, Deledda C, Rosati F, et al. New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm. Front Neuroendocrinol. 2009;30:119-29 pubmed publisher
    ..This review describes how this protein interacts with cholesterol and estrogens, thus generating a neuroprotective network, that might open new possibilities in the prevention/treatment of neurodegenerative diseases. ..
  49. Di Stasi D, Vallacchi V, Campi V, Ranzani T, Daniotti M, Chiodini E, et al. DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress-induced apoptosis. Int J Cancer. 2005;115:224-30 pubmed
  50. Rolletschek H, Borisjuk L, Sánchez García A, Gotor C, Romero L, Martínez Rivas J, et al. Temperature-dependent endogenous oxygen concentration regulates microsomal oleate desaturase in developing sunflower seeds. J Exp Bot. 2007;58:3171-81 pubmed
    ..It is concluded that a major mechanism by which temperature modifies the unsaturation degree of the sunflower oil is through its effect on dissolved oxygen levels in the developing seed. ..
  51. Cecchi C, Rosati F, Pensalfini A, Formigli L, Nosi D, Liguri G, et al. Seladin-1/DHCR24 protects neuroblastoma cells against Abeta toxicity by increasing membrane cholesterol content. J Cell Mol Med. 2008;12:1990-2002 pubmed publisher
    ..Our findings extend recently reported data indicating that seladin-1 overexpression directly enhances the resistance to Abeta toxicity featuring seladin-1/DHCR 24 as a possible new susceptibility gene for sporadic AD. ..
  52. Miura A, Kameya M, Arai H, Ishii M, Igarashi Y. A soluble NADH-dependent fumarate reductase in the reductive tricarboxylic acid cycle of Hydrogenobacter thermophilus TK-6. J Bacteriol. 2008;190:7170-7 pubmed publisher
    ..This is the first report of a soluble NADH-dependent FRD in Bacteria and of the purification of a FRD that operates in the reductive tricarboxylic acid cycle. ..
  53. Chen L, Maloney K, Krol E, Zhu B, Yang J. Cloning, overexpression, purification, and characterization of the maleylacetate reductase from Sphingobium chlorophenolicum strain ATCC 53874. Curr Microbiol. 2009;58:599-603 pubmed publisher
    ..In addition, the purified PcpE was able to restore PCP-degrading capability to S. chlorophenolicum strain ATCC 39723, implicating that there was no functional PcpE in the ATCC 39723 strain...