Aldo-keto-reductase enzymes

Aldose reductase (ALR2 EC 1.1.1.21) is an 36 kDa enzyme that catalyzes the reduction of a wide range of carbonyl-containing compounds to their corresponding alcohols. It is a member of an extensive aldo-keto oxidoreductase enzyme family, a collection of structurally similar proteins expressed in both animals and plants. Most members of the enzyme family possess similarities in molecular mass, pH optimum, coenzyme dependence, and demonstrate overlapping specificity for many substrates and inhibitors. 

Carbonyl Reductase Inhibition (Aldo-Keto-Reductase Family of Enzymes)... 

The enzyme giving (ft)-4-chIoro-3-hydroxybutanoate esters was isolated in crystalline form from S. salmonicolor and was characterized in some detail [111-113], It is a kind of aldehyde reductase with a molecular mass of about 37,000. The enzyme absolutely requires NADPH as a cofactor. Besides 4-haloacetoacetate esters, p-nitrobenzaldehyde and a variety of other aromatic and aliphatic aldehydes have been found to be reduced well by the enzyme (see Tables 4 and 5). The structural gene of the enzyme was cloned and the enzyme has shown to have similarity to the mammalian aldo-keto-reductase superfamily enzymes in primary protein structure [114], In S. salmonicolor, the enzyme comprised 2 6% of the total extractable proteins. Such a high content of the enzyme suggests that this may be one of the reasons why the yeast catalyzes conversion to the (R)-enantiomer predominantly. 

Dehydrogenases often act primarily to reduce a carbonyl compmmd rather than to dehydrogenate an alcohol. These enzymes may still be called dehydrogenases. For example, in the lactic acid fermentation lactate is formed by reduction of pyruvate but we still call the enzyme lactate dehydrogenase. In our bodies this enzyme functions in both directions. However, some enzymes that act mainly in the direction of reduction are called reductases. An example is aldose leductase, a member of a family of aldo-keto reductases which have (a / P)g-barrel structures. ... 

Diverse soluble enzymes, called aldo-keto reductases. cany out bioreduction of aldehydes and ketones. They are found in the liver and other tissues (e.g.. kidney). As a general class, these soluble en7.ynie.s have similar physi-ochemical properties and broad substrate specificities and require NADW as a cofactor. Oxidoreductase enzymes that catty out both oxidation and reduction reactions also can reduce aldehydes and ketones. " For example. Ihe important liver alcohol dehydrogenase is an NAD -dependent oxido-icductase that oxidizes ethanol and other aliphatic alcohols to aldehydes and ketones. In the presence of NADH or... 

The aldo-keto reductases (AKR), a complex superfamily of enzymes, which includes aldehyde reductases (ALR) and dihydrodiol dehydrogenase (DD). 

Activation of polycyclic aromatic hydrocarbon trans-diliydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung adenocarcinoma (A549) cells. J. Biol. Chem., 277, 24799-24808. 

Discrete plant KRs have been identified that interact with CHS for the biosynthesis of 6 -deoxychalcone (20) (Fig. 3D) [133, 136-139]. Interestingly, the plant KR has no similarity with those that catalyze the reduction of the poly- -ketone intermediates in polyketide or fatty acid biosynthesis [49, 50, 81-84]. Instead it is similar to various aldo/keto-reductases, mostly from carbohydrate metabolism [139-141], and contains a leucine zipper motif known to be involved in protein-protein interaction [142]. Plant 0-methyltransferases are well known [143], but enzymes for C-methylation have not been described. The... 

PAHs are metabolized by a variety of xenobiotic-metabolizing enzymes (Baird et al., 2005). CYP and epoxide hydrolase eonvert the PAH into PAH-diols and these products are transformed in metabolites, potentially, carcinogenic, by the CYP aetion, forming PAH diol-epoxides or by the Aldo-keto-reductase action, generating PAH o-quinones. PAHs can be also activated by CYP and by peroxidases, forming the reactive cations radicals, which bind, covalently, to DNA. Intermediary products formed are still metabolized by enzymes of phase 11, resulting in metabolites more polars and soluble in water becoming ready to be excreted by the body (Shimada, 2006). 

PKR is a NADPH-dependent monomeric enzyme of 34 to 35 kDa belonging to the aldo-and keto-reductase superfamily.The first isolation and characterization of a PKR cDNA was from G. max The G. max cDNA, and cDNAs from other species, have been used to confirm the PKR activity of the recombinant protein, and to produce larger protein amounts for structural analysis.Studies of the recombinant protein, and analysis of 35SCaMV PKR transgenic plants, have also shown that PKR is able to function with CHS proteins from nonlegume species that synthesize only the common 5-hydroxyflavonoids. 

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