Medium-chain dehydrogenase/reductase

Kurata A, T Kurihara, H Kamachi, N Esaki (2005) 2-haloacrylate reductase a novel enzyme of the medium-chain dehydrogenase/reductase superfamily that catalyzes the reduction of carbon-carbon double bond of unsaturated organohalogen compounds. J Biol Chem 280 20286-20291. 

The ALDs are a subset of the superfamily of medium-chain dehydrogenases/reductases (MDR). They are widely distributed, cytosolic, zinc-containing enzymes that utilize the pyridine nucleotide [NAD(P)+] as the catalytic cofactor to reversibly catalyze the oxidation of alcohols to aldehydes in a variety of substrates. Both endobiotic and xenobiotic alcohols can serve as substrates. Examples include (72) ethanol, retinol, other aliphatic alcohols, lipid peroxidation products, and hydroxysteroids (73). 

Medium-chain dehydrogenases/ reductases (Figs. 2A, 3A) Total length of ca. 350 residues Mr 40 kDa All 44... 

B Persson, JS Zigler, H Jornvall. A superfamily of medium-chain dehydrogenases/ reductases (MDR). Eur J Biochem 226 15-22, 1994. 

CAD is a type A reductase, abstracting the prol hydride from NADPH via a two-electron hydride transfer mechanism. It belongs to the alcohol dehydrogenase (ADH) family, the members of which are zinc-dependent medium-chain dehydrogenases/reductases (MDR) with two Zn ions per subunit. One zinc atom is thought to have a structural role, whereas the other forms the core of the catalytic site. Interestingly, medium-chain zinc-dependent ADHs exist as homotetramers as in bacteria, archaea, and yeast, or as homodimers as in plants and vertebrates. 

Knoll, M. and Pleiss, J. (2008) The medium-chain dehydrogenase/reductase... 

E. Nordling, H. Jomvall, B. Persson, Medium-chain dehydrogenases/reductases (MDR). Family characterizations including genome comparisons and active site modelling, Eur. J. Bio-chem. 269 (2002) 4267-4276. 

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. 

Pares, X., J. Farres, N. KedishvUi, and G. Duester. 2008. Medium-Chain and Short-Chain Dehydrogenases/Reductases in Retinoid Metabolism. Cell Mol Life Sci 65, no 24 3936 9. 

As many as 1 in 10,000 persons may inherit such prob-lems.48 50a Tire proteins that may be defective include a plasma membrane carnitine transporter carnitine palmitoyltransferases camitine/acylcamitine trans-locase long-chain, medium-chain, and short-chain acyl-CoA dehydrogenases 2,4-dienoyl-CoA reductase (Eq. 17-1) and long-chain 3-hydroxyacyl-CoA dehydrogenase. Some of these are indicated in Fig. 17-2. 

The final member of the yeast medium-chain alcohol dehydrogenase superfamily, encoded by the ZTA1 gene, differs in several key aspects from the six putative yeast reductases shown in Fig. 3A. Most important, this enzyme lacks the residues that ligate the catalytic Zn(II) ion, in common with other crystallin homologs. Related metal-free proteins are capable of reducing quinones [53] however, the catalytic activity and substrate specificity of the protein encoded by ZTA1 is currently unknown. 

Glutaric acidemia type II is caused by defects in the ETF/ETF-QO proteins. The clinical manifestations of these disorders are similar to medium-chain acyl-CoA dehydrogenase deficiency (discussed later). The double bond formed by the acyl-CoA dehydrogenase has a trans configuration. The double bonds in naturally occurring fatty acids are generally in the cis configuration. The oxidation of unsaturated m-fatty acids requires two auxiliary enzymes, enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. 

A wide variety of different cytochrome-linked electron-transfer systems is encountered in bacteria respiratory chains with oxygen, nitrate or sulphate as electron acceptors, fumarate reductase systems and light-driven cyclic electron-transfer systems (Fig. 3). All these systems are composed of several electron-transfer carriers, the nature of which varies considerably in different organisms. Electron carriers which are most common in bacterial electron-transfer systems are flavoproteins (dehydrogenases), quinones, non-heme iron centres, cytochromes and terminal oxidases and reductases. One common feature of all electron-transfer systems is that they are tightly incorporated in the cytoplasmic membrane. Another important general property of these systems is that electron transfer results in the translocation of protons from the cytoplasm into the external medium. Electron transfer therefore... 

It is, however, better known that flavoenzymes (i.e., enzymes utilizing the flavin adenine dinucleotide [FAD FADH2] redox system) mediate the introduction of a,P carbon-carbon double bonds into carboxylic acids and into acetyl Coenzyme A (acetyl CoA) thioesters of long-, medium-, and short-chain fatty acids. In carboxylic acids, such as those of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11) the oxidation is affected by the enzyme sucdnate dehydrogenase (fumerate reductase— EC 1.3.99.1), which utilizes the cofactor flavin adenine dinucleotide (FAD) The latter is reduced to FADH2 and an ( )-double bond is introduced. The process shown in Scheme 9.105, for the conversion of succinate (1,4-butanedioic acid) to fumerate [(E)-l,4-butenedioic acid], is a fragment of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11), which is the pathway commonly utilized for oxidative degradation of acetate to carbon dioxide. 

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