Enoyl-CoA reductase

Fig. 14.1. Role ofthe pyruvate dehydrogenase complex (PDC) during aerobic/ anaerobic transitions in the development of Ascaris suum. PDC, pyruvate dehydrogenase complex AD, acyl CoA dehydrogenase ER, enoyl CoA reductase FR, fumarate reductase SDH, succinate dehydrogenase.

Eipi (Wheelock etal., 1991) Eipil (Huang and Komuniecki, 1997) E3BP, E3-binding protein (p45) E3 ER, enoyl CoA reductase (Duran etal. 1993, 1998) AAT, adenine nucleotide translocase a-tubulin. UE, unembryonated egg L1, first-stage larva L2, second-stage larva L3, third-stage larva M, adult muscle ... 

Duran, E., Komuniecki, R.W., Komuniecki, P.R., Wheelock, M.J., Klingbeil, M.M., Ma, Y.C. and Johnson, K.R. (1993) Characterization of cDNA clones for the 2-methyl branched-chain enoyl-CoA reductase. An enzyme involved in branched-chain fatty acid synthesis in anaerobic mitochondria of the parasitic nematode Ascaris suum. Journal of Biological Chemistry 268, 22391—22396. 

Fig. 5.2. Possible metabolic pathways in facultative anaerobic mitochondria. Shaded boxes show components of the electron-transport chain used during hypoxia, open boxes are components used during aerobiosis, and the hatched boxes (complex I and ATP-synthase) are components used under aerobic as well as anaerobic conditions. ASCT acetate succinate CoA-transferase, C cytochrome c, Cl, CIII and CIV complexes I, III and IV of the respiratory chain, CITR citrate, ECR enoyl-CoA reductase (such as present in Ascaris suum), ETF electron-transfer flavoprotein, ETF RQ OR electron-transfer flavoproteimrhodoquinone oxidoreductase, FRD fumarate reductase, FUM fumarate, MAE malate, OXAC oxaloacetate, PYR pyruvate, RQ rhodoquinone, SDH succinate dehydrogenase, SUCC succinate, Succ-CoA succinyl-CoA, TER trans-2-enoyl-CoA reductase (such as present in E. gracilis), UQ ubiquinone...

Fig. 5.3. The major components involved in mitochondrial NADH oxidation in facultative anaerobic mitochondria. In anaerobically functioning mitochondria, NADH is oxidized either by soluble enzymes (left) or by membrane-bound complexes of the electron-transport chain (middle). Under aerobic conditions, a classic respiratory chain is used to oxidize NADH (right). Proton translocation is indicated by H with arrows. Ovals represent the electron transporters RQ, UQ and cytochrome c (cyt. c), and electron transport is indicated by dashed arrows. The vertical bar represents a scale for the standard redox potentials in millivolts. Fum fumarate, NADH-DH NADH dehydrogenase, NADH-ECR soluble NADH enoyl-CoA reductase, RQH2 rhodoquinol, Succ succinate, UQH2 ubiquinol...

As described before, also the formation of branched-chain fatty acids by enoyl-CoA reductase activity is coupled to electron transport (Komuniecki and Harris 1995). In this case electrons are transported from NADH to rhodoquinone via complex I and subsequently to the electron-transfer flavoprotein (ETF) via ETF-reductase (Fig. 5.3). The soluble, non-membrane-bound ETF then transfers electrons to enoyl-CoA reductase, which uses the electrons for the condensation of two short-chain (C2-C3) acyl-CoA moieties for the formation of branched-chain fatty acids. 

Hoffmeister M, Piotrowski M, Nowitzki U, Martin W (2005) Mitochondrial trans-2-enoyl-CoA reductase of wax ester fermentation from Euglena gracilis defines a new family of enzymes involved in lipid synthesis. J Biol Chem 280 4329-4338... 

A second system for fatty acid elongation exists in the mitosol, probably for provision of long fatty acids for mitochondrial structure. This system uses most of the same activities of 9-oxidation, but an NADPH dependent Enoyl-CoA reductase replaces the FAD dependent dehydrogenase. 

Osmundsen H, Cervenka J. Bremer J. Arole for 2,4-enoyl-CoA reductase in mitochondrial fl-oxidalion of polyunsaturated fatty acids. Effects of treatment with clofibrate on oxidation of polyunsaturated acylcarnitines by isolated rat liver. Biochem J 1982 208 749-757. 

Enoyl-CoA reductase EC 1.3.1.38 NADPH-dependent saturation of a,/3-unsaturated acyl-CoAs... 

Fig. 1. Reactions in the two-carbon chain elongation of long-chain fatty acids in the ER. Elovl, elongation of long-chain fatty acids KAR, 3-ketoacyl-CoA reductase TER, rrons-2,3-enoyl-CoA reductase.

Mitochondrial elongation occurs by successive addition and reduction of acetyl units in a reversal of fatty acid oxidation. Although fatty acid P-oxidation and mitochondrial chain elongation have the same organelle location, reversal of a tra/ii-2-enoyl-CoA reductase P-oxidation is not feasible the FAD-dependent acyl-CoA dehydrogenase of P-oxidation is substituted by a more thermodynamically favorable enzyme reaction, catalyzed by NADPH-dependent enoyl-CoA reductase, to produce overall negative free-energy for the sequence. Enoyl-CoA reductase firom liver mitochondria is distinct from... 

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

Table 2 reveals the multitude of catalysed reactions and Table 3 shows the surprising broad substrate specificity of enoate reductase from Clostridium tyrobutyricum DSM 1460. For a series of substrates Table 3 shows kinetic data (6,8,18,20,24). Only a few of these substrates can not be prepared in a sterical pure form with whole cells or crude extract from C. tyrobutyricum without additional measures. There are two aspects which have to be emphasized Whole cells contain a 2-enoyl-CoA reductase (EC 1.3.1.8) besides enoate reductase (EC 1.3.1.31) (Scheme 3). After offering ( )-2-butenoate, ( )-... 

SCHEME 3 A few 2-enoates (see text) are reduced by enoate reductase or cfter activation to a 2-enoyl-CoA-ester also by enoyl-CoA reductase. The stereochemical course of both reactions is different (25). In resting cells of C. tyrobutyricum the reaction of enoyl-CoA reductase can be blocked (Section 2.5.3). 

The specific activities of ferredoxin-NAD oxidoreductase and butyiyl-CoA dehydrogenase (enoyl-CoA reductase. Scheme 3) increased 3-4 fold during growth on crotonate... 

EPA and DHA are fundamental EPAs from co-3 series of LCPUFAs. DHA is the main structural component of cell membranes, at high level in brain tissue and retina. DHA is formed from EPA by peroxisomal p-oxidation (Burdge and Calder, 2005). EPA and DPA (22 5, co-3) can also be synthesized from DHA via p-oxidation in peroxisomes by catalytic activity of probably A-4 enoyl CoA reductase and A-2 enoyl CoA isomerase (Gr0rm et ah, 1991). 

Borrebaek, B., Osmundsen, H. Bremer, J. (19W) Biochem. Biophys. Res. Comntun., 93, 1173-1180, In vivo induction of 4-enoyl-CoA reductase by clofibrate in liver mitochondria and its effect on pent-4-enoate metabolism. 

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