Dihydroquercetin reductase

Reddy, A.R. et al.. The Al (anthocyanin-1) locus in Zea mays encodes dihydroquercetin reductase. 

A similar dihydroquercetin reductase activity has been shown to be a key step in the biosynthesis of anthocyanidins (Stafford, 1989). The enzyme from Dahlia has a molecular weight of about 41,000. However, there is evidence that the specificity of 3-hydroxyflavanone reductases of anthocy-anidin biosynthesis are distinct from those of flavan-3,4-diol biosynthesis (Stafford, 1989) see Chapter 11). 

Dihydroflavonol 4-reductase (DFR) catalyzes the stereospecific conversion of 2R,3R)-trans-DHFs to the respective (2R,35, 45)-flavan-2,3-traKi-3,4-cA-diols (leucoanthocyanidins) through a NADPH-dependent reduction at the 4-carbonyl. DNA sequences for DFR were first identified from A. majus and Z. mays, and the identity of the Z. mays sequence confirmed by in vitro transcription and translation of the cDNA and assay of the resultant protein. DNA sequences have now been cloned from many species, with the size of the predicted protein averaging about 38kDa. Stereospecificity to (2R,3R)-dihydroquercetin (DHQ) has been shown for some recombinant DFR proteins. ... 

Some bioactive flavonols include aldose reductase inhibitors (axillarin (5,7,3, 4 -tetrahy-droxy-6-methoxyflavone), 2,3-dihydroquercetin (taxifolin), 6-hydroxykaempferol (galetin), hyperin (quercetin 3-0-galactoside), isoquercetrin, morin (3,5,7,2, 4 -pentahydroxy-flavone), quercetin, quercitrin and rutin) anti-inflammatory 5-LOX inhibitors (fisetin (3,7,3, 4 -tetrahydroxyflavone), kaempferol, morin, myricetin, quercetin and rutin) a GOX inhibitor (galangin (3,5,7-trihydroxyflavone)) iodothyronine deiodinase inhibitors (fisetin, kaempferol and morin) NADH and succinate dehydrogenase inhibitors (fisetin and myricetin) and protein kinase inhibitors (fisetin, galangin, isorhamnetin, kaempferide... 

Stafford, H., Lester, H. (1984). Flavan-3-ol biosynthesis the conversion of (-l-)-dihydroquercetin and flavan-3,4-cis-diol (leucocyanidin) to (-t) catechin by reductases extracted from cell suspension cultures of Douglas fir. Plant Physiol., 76, 184-186. 

By reduction of dihydroquercetin and dihydromyricetin, operated by the enzyme dihydroflavonol-4-reductase (DFR) (in vine the reduction of dihydrokaempferol does not occur), 2,3-trans leucocyanidin and leucodelphinidin form. Successive synthesis of (+)-catechin and (+)-gallocatechin (2,3-trans isomers) is mediated by the enzyme leucoan-thocyanidin reductase (LAR). On the other hand, the synthesis of (—)-epicatechin and (—)-epigallocatechin (2,3-cis isomers) proceeds via oxidation of 2,3-trans leucoanthocyanins into cyanidin and delphinidin (accompanied with chirality loss) mediated by the enzyme leucoan-thocyanidin dioxygenase (LDOX), which is followed by the reduction catalyzed by the enzyme anthocyanidin reductase (ANR) with reacquisition of chrality (Fujita et al., 2005). 

The reduction of 3-hydroxyflavones (dihydroflavanols) to 3,4-diols (leucoanthocyanidins) was first demonstrated in cell-free extracts of Pseudotsuga menziesii and Ginkgo bi-loba, by the reduction of (-I- )-dihydroquercetin with dihy-droflavonol 4-reductase in the presence of NADPH to a 2,3-trans-3,4-cis-diol which differs from the product of nonen-zymatic reduction, 2,3-trans-3,4-trans-diol (2R,3S,4R)-(+ )-3,4,5,7,3, 4 -hexahydroxyflavan (Fig. 11.15 of Chapter 11). This result has now been confirmed in several other plant systems (Heller and Forkmann, 1988 Stafford, 1989). 

Dihydroflavonol 4-reductase (DFR) is involved in the biosynthesis of anthocyanins and proanthocyanidins (PAs). DFRs catalyze the stereospecific reduction of (2R,3R)-dihydrofla-vonols to (2R,3R,45)-leucoanthocyanidins [77] (Fig. 5). Petunia possesses three different DFR genes (dfrA-C), but only dfrA is transcribed in floral tissues. DFR-A does not accept dihy-drokaempferol, the precursor for the synthesis of pelar-gonidin-type anthocyanins. Consequently, no orange-colored petunia flowers are foimd in nature [89]. Dihydroquercetin and (hhydramyrice-tin are also substrates for DFRs and provide leu-cocyanidin and leucodelphinidin, respectively. 

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