Hydroxyacyl coenzyme dehydrogenase

The third reaction of this cycle is the oxidation of the hydroxyl group at the /3-position to produce a /3-ketoacyl-CoA derivative. This second oxidation reaction is catalyzed by L-hydroxyacyl-CoA dehydrogenase, an enzyme that requires NAD as a coenzyme. NADH produced in this reaction represents metabolic energy. Each NADH produced in mitochondria by this reaction drives the synthesis of 2.5 molecules of ATP in the electron transport pathway. L-Hydroxyacyl-... 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Treem WR et al Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Hepatology 1994 19 339. 

Yang and Schulz also formulated a treatment of coupled enzyme reaction kinetics that does not assume an irreversible first reaction. The validity of their theory is confirmed by a model system consisting of enoyl-CoA hydratase (EC 4.2.1.17) and 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) with 2,4-decadienoyl coenzyme A as a substrate. Unlike the conventional theory, their approach was found to be indispensible for coupled enzyme systems characterized by a first reaction with a small equilibrium constant and/or wherein the coupling enzyme concentration is higher than that of the intermediate. Equations based on their theory can allow one to calculate steady-state velocities of coupled enzyme reactions and to predict the time course of coupled enzyme reactions during the pre-steady state. 

LCHAD long-chain 3-hydroxyacyl-coenzyme A dehydrogenase... 

Treem, W.R., Rinaldo, P., Hale, D.E., Stanley, C.A., Millington, D.S., Hyams, J.S., Jackson, S., Turnbull, D.M. Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency Hepatology 1994 19 339-345... 

LeFlir M, Dubach U. Peroxisomal and mitochondrial b-oxidation in the rat kidney. Distribution of fatty acyl coenzyme A oxidase and 3-hydroxyacyl-coenzyme A dehydrogenase activities along the nephron. J Flistochem Cytochem 1982 30 441-444. 

Carpenter K, PoUitt RJ, Middleton B. Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria. Biochem Biophys Res Commun 1992 183 443-8. 

As noted above, there have been reports that link some cases of APLP with a defect in fatty acid metabolism in the fetus. These include fetal deficiencies of long chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), carnitine-palmitoyl transferase 1 (CPT 1), and medium chain acyl-coenzyme A dehydrogenase (MCAD). The mechanism by which defective fetal fatty acid oxidation causes maternal illness is not known. However, since the fetus uses primarily glucose metabolism for its energy needs, it is likely that toxic products from the placenta, which does use fatty acid oxidation, cause the maternal liver failure. 

Rakheja D, Bennett MI, Rogers BB. Long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency A molecular and biochemical review. Lab Invest 2002 82 815-24. 

Dichlorophenoxy)butyric acid is converted in the presence of ATP into dichlorophenoxybutyryl coenzyme A. This acyl-CoA is converted by the electron acceptor flavine adenine dinucleotide (FAD) into dichlorophenoxycrotonyl-CoA. One carbon atom of the unsaturated bond is hydroxilated and dichlorophenoxy- -hydroxybutyric acid-CoA is formed. In certain plants possessing specific /3-oxidase enzyme systems, -ketobutyric acid-CoA is formed from this intermediate compound by the mediation of NAD and NADH in a reaction catalysed by -hydroxyacyl-CoA dehydrogenase. This compound is decomposed by hydrolysis into 2,4-D and acetyl-CoA. 

Uchida, Y., Izai, K., Orii, T., and Hashimoto, T. Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydra-tase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein. J Biol Chem 267 (1992) 1034-1041. 

He, X.-Y. Yang, S.-Y. (1998) Biochim. Biophys. Acta. 1392, 119-126. Molecular cloning, expression in Escherichia coli, and characterization of a novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver. 

Hartmann, D., Philipp, R., Schmadel, K., Birktoft, J.J., Banaszak, L.J. Trommer, W.E. (1991) Biochenistry 30, 2782-2790. Spatial arrangement of coenzyme and substrates bound to L-3-hydroxyacyl-CoA dehydrogenase as studied by spin-labeled analogues of NAD and CoA. 

Schifferdecker, J. Schulz, H. (1974) Life Sci. 14, 1487-1492. The inhibition of L-3-hydroxyacyl-CoA dehydrogenase by acetoacetyl-CoA and the possible effect of this inhibitor on fatty acid oxidation. Waterson, R. Hill, R. (1972) J. Biol. Chem. 247, 5258-5265. Enoyl coenzyme A hydratase (crotonase). Catalytic properties of crotonase and its possible regulatory role in fatty acid oxidation. 

Long-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase (LCHAD) Deficiency... 

Van Hove JL, et al. Acylcamitines in plasma and blood spots of patients with long-chtiin 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. J Inherit Metab Dis. 2000 23(6) 571-82. 

Duran M, Wanders RJ, de Jager JP, Dorland L, Bruinvis L, Ketting D, et al. 3-hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme a dehydrogenase deficiency associated with sudden neonatal death protective effect of medium-chain triglyceride treatment. Eur J Pediatr. 1991 150(3) 190-5. PubMed PMID 2044590, Epub 1991/01/01. eng. 

P. putida KTOY06 was genetically engineered by the deletion of the genes of 3-ketoacyl-coenzyme A (CoA) thiolase (fadA) and 3-hydroxyacyl-CoA dehydrogenase (fadB). The P-oxidation pathway was weakened and therefore the carbon source tetradecanoic acid was converted to a mcl-PHA containing 31 9 mol% (R)-3-hydroxytetradecanoic acid as the main component, whereas the (R)-3-hydroxyhexanoic acid content remained almost constant at 3 mol%. The mechanical properties were influenced by the content of (R)-3-hydroxydodecanoic or (R)-3-hydroxytetradecanoic acid, respectively, as can be derived from Table 1. 

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