Sorbitol dehydrogenase

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Sorbitol dehydrogenase
Sorbitol dehydrogenase
Ribbon model of the tetramer, NAD and zinc as domes, according to PDB  1PL8
Properties of human protein
Mass / length primary structure 356 amino acids
Secondary to quaternary structure Homotetramer
Cofactor Zinc, NAD
Identifier
Gene name SORD
External IDs
Enzyme classification
EC, category 1.1.1.14 ,  oxidoreductase
Response type oxidation
Substrate Sorbitol + NAD +
Products Fructose + NADH
Occurrence
Parent taxon Creature
Orthologue
human House mouse
Entrez 6652 20322
Ensemble ENSG00000140263 ENSMUSG00000027227
UniProt Q00796 Q64442
Refseq (mRNA) NM_003104 NM_146126
Refseq (protein) NP_003095 NP_666238
Gene locus Chr 15: 45.02 - 45.08 Mb Chr 2: 122.23 - 122.27 Mb
PubMed search 6652 20322

Sorbitol dehydrogenase (Sdh) ( Gen : SORD ) is the name for enzymes that convert sorbitol to fructose . This is the second step in the polyol pathway used by cells to produce fructose from glucose without consuming ATP . Every living being uses Sdh. In mammals, the enzyme is active in all tissue types.

There is evidence that polymorphisms in the SORD gene are associated with reticulopathy in type 2 diabetes mellitus . Sdh inhibitors (or aldose reductase inhibitors) can prevent the occurrence of neurological and ophthalmological problems in diabetes and are therefore of interest as potential drugs.

Structure and function

Sdh forms a complex tetramer that is given its special shape by a network of hydrogen bonds . This mechanism has been preserved in all mammals and is essential for the function of the enzyme.

The catalyzed reaction:

D-sorbitol+ NAD (P) + ⇔ D-fructose+ NAD (P) H / H +

D-sorbitol is dehydrated to D-fructose and vice versa.

Individual evidence

  1. ↑ El-Kabbani O, Darmanin C, Chung RP: Sorbitol dehydrogenase: structure, function and ligand design . In: Curr. Med. Chem . 11, No. 4, February 2004, pp. 465-76. doi : 10.2174 / 0929867043455927 . PMID 14965227 .
  2. ↑ UniProt Q00796
  3. ↑ Szaflik JP, Majsterek I, Kowalski M, et al : Association between sorbitol dehydrogenase gene polymorphisms and type 2 diabetic retinopathy . In: Exp. Eye Res . 86, No. 4, April 2008, pp. 647-52. doi : 10.1016 / j.exer.2008.01.009 . PMID 18289528 .
  4. ↑ Schmidt RE, Dorsey DA, Beaudet LN, et al : A potent sorbitol dehydrogenase inhibitor exacerbates sympathetic autonomic neuropathy in rats with streptozotocin-induced diabetes . In: Exp. Neurol. . 192, No. 2, April 2005, pp. 407-19. doi : 10.1016 / j.expneurol.2004.12.018 . PMID 15755558 .
  5. ↑ Kador PF, Inoue J, Blessing K: Anticataract activity of analogs of a sorbitol dehydrogenase inhibitor . In: J Ocul Pharmacol Ther . 20, No. 4, August 2004, pp. 333-44. doi : 10.1089 / 1080768041725281 . PMID 15321028 .
  6. ↑ Hellgren M, Kaiser C, de Haij S, Norberg A, Höög JO: A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power . In: Cell. Mol. Life Sci. . 64, No. 23, December 2007, pp. 3129-38. doi : 10.1007 / s00018-007-7318-1 . PMID 17952367 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Fructose, Mannose and Fucose Metabolism  - Learning and Teaching Materials