Hydroxyacyl coenzyme

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

The presence of a PHA synthase alone is not sufficient to allow synthesis of PHAs. PHA biosynthesis will not occur if genes encoding enzymes required for the synthesis of hydroxyacyl-coenzyme A thioesters are absent or if the pathways constituted by these enzymes are for whatever reason not functionally active. This becomes evident, for example, when a PHA synthase gene is expressed in wild type or normal laboratory strains of E. coir, even if a functionally active PHA synthase is expressed, no or only traces of PHAs are accumulated. 

There are an overwhelming number of studies which successfully demonstrated heterologous expression of PHA synthesis genes in bacteria it will therefore not be possible to mention them all. Establishment of functional active PHA biosynthesis pathways in E. coli requires not only a PHA synthase but also enzymes that allow the conversion of metabolites, which derive from the provided carbon source, into the R isomers of hydroxyacyl-coenzyme A thioesters that are used as a substrate by the respective PHA synthase. Otherwise, no or only marginal amounts of PHAs are accumulated. 

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. 

The quantitative determination of PhaC activity and their substrate range in vitro is one of the obstacles in PHA research. One limiting factor is the limited availability of hydroxyacyl coenzyme A thioesters which have to be used as substrates to measure the polymerization reaction. Whereas 3-hydroxybutyryl-CoA is commercially available or can be relatively easily synthesized, all other hydroxyacyl-CoA esters are not commercially available and have to be synthesized by tedious methods [16]. 

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. 

Yang, S.-Y, He, X.-Y. Schulz, H. (1995) Biochemistry 34, 6441-6447. Glutamate 139 of the large a-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of A , A -enoyl coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli. 

Yang, S.-Y. Elzinga, M. (1993)7. Biol. Ghem. 268, 6588-6592. Association of both enoyl coenzyme A hydratase and 3-hydroxyacyl coenzyme A epimerase with an active site on the amino-terminal domain of the multifunctional fatty acid oxidation protein from Escherichia coli. 

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. 

The microorganisms produce poly(hydroxyalkanoate)s using R- -hydroxyacyl-Coenzym-A enz5mcies as the direct metabolic substrate for a poly(hydroxyalkanoate) S5mthase. 

Bennett MJ, Spotswood SD, Ross KF, Comfort S, Koonce R, Boriack RL et al. Fatal hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency clinical, biochemical, and pathological studies on three subjects with this recently identified disorder of mitochondrial beta-oxidation. Pediatr Dev Pathol 1999 2 337-345. 

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