Beta-oxidation enzymes

M (32% increase in liver weights 178% increase in peroxisomal beta-oxidation enzyme activity)... 

Ferdinandusse, S., Denis, S., Mooijer, PA. etal., Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid, J. Lipid Res., 42, 1987, 2001. 

In mammals, complex lipids are catabolised by lipases to yield fatty acids, glycerol and other components. The fatty acids are then broken down by beta-oxidation to give NADH, reduced flavoprotein and acetyl-CoA, which then enters the tricarboxylic acid cycle. Lipase activity has been detected in several cestodes (513, 772) but there is no evidence for an active beta-oxidation sequence in any species investigated to date. Somewhat surprisingly, however, some of the beta-oxidation enzymes have been... 

Table 4.11. The activities of the beta-oxidation enzymes in cestodes (Data from Barrett, 1983)... 

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. 

Hashimoto, T., Peroxisomal beta-Oxidation Enzymes, Cell Biochem. Biophys., 32 63-72, 2000. 

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. 

To further investigate different expression patterns in these three tissues, we subdivided the metabolism TUGs based on substrate classes. Thus, carbohydrate includes all glycoside hydrolases, lipid includes lipases, beta-oxidation enzymes, JH-metabolizing enzymes, etc., and protein includes proteases. TUGs for all subcategories are contributed by all three insects, with the exception of the mevalonate pathway, which is represented only by /. pini (Fig. 3.2). This further supports the observation that their presence in /. pini midguts reflects the pheromone-biosynthetic activity of that tissue. 

Sumegi, B., Z. Porpaczy 1. Alkonyi % ) Biochim. Biophys. Acta. 1081, 121-128. Kinetic advantage of the interaction between the fatty acid beta-oxidation enzymes and the complexes of the respiratory chain. 

Schram, A.W., Strijland, A., Hashimoto, T., Wanders, R.J.A., Schutgens, R.B.H., van den Boseh, H. Tager, J.M. (1986) Proc. Natl. Acad Sci. U. S. A. 16, 6156-6158. Biosynthesis and maturation of peroxisomal beta-oxidation enzymes in fibroblasts in relation to the Zellweger syndrome and infantile Refsum disease. 

A 32% increase in liver weights, along with a 187% increase in peroxisomal beta-oxidation activity, was noted in rats exposed to 1,000 mg/kg/day MIL-H-5606 for 26 days (Mattie et al. 1993). The toxicological significance of the changes in peroxisomal enzyme activities is unclear. 

In order to carry out all of these different functions, peroxisomes are equipped with a unique set of enzyme proteins, catalysing the different reactions involved. In addition, the peroxisomal membrane contains specific transporters in order to take up substrates from the cytosol and release the end products of peroxisomal metabolism. Since peroxisomes lack a citric acid cycle as well as a respiratory chain, the end products of peroxisomal metabolism, such as acetyl-CoA, propionyl-CoA and a range of other acyl-Co A esters predominantly derived from fatty acid beta-oxidation, are exported from the peroxisomal interior and shuttled to mitochondria for full oxidation to C02 and H20. The same applies to the NADH produced during beta-oxidation, which is reoxidised via redox-shuttles so that the NADH generated in peroxisomes is ultimately reoxidised in the mitochondrial respiratory chain at the expense of molecular oxygen. 

Group 2 contains the single peroxisomal enzyme deficiencies [14]. This group is also subdivided in different classes, including the peroxisomal beta-oxidation deficiencies (X-linked adrenoleucodystrophy, X-ALD), acyl-CoA oxidase 1 deficiency... 

Ward, C. W. Fairbairn, D. (1970). Enzymes of beta-oxidation and the tricarboxylic acid cycle in adult Hymenolepis diminuta (Cestoda) and Ascaris lumbricoides (Nematoda). Journal of Parasitology, 56 1009-12. 

Chemicals that damage mitochondrial structure, enzymes, or DNA synthesis can disrupt beta oxidation of hpids and oxidative energy production within hepatocytes. Prolonged interruption of beta oxidation leads to micro-vesicular steatosis which can progress to macrovesicular steatosis. This sequence of events has been noted with alcoholic and nonalcoholic steatohepatitis. The role of mitochondria has been extensively studied with nonalcoholic fatty hver disease, a major issue in human medicine. Alcoholic steatosis and other forms of hepatic steatosis have been linked to impairment of ATP homeostasis and mitochondrial abnormalities have been reported in a growing body of hterature. 

The nature of the active site in beta-amylase is not unambiguously known for enzymes from different sources. Early experiments on purified barley and on malted barley first indicated, from studies of the modification of the enzyme with nitrous acid and ketene, that free tyrosine and sulfhydryl groups are essential for activity, whereas free a-amino groups are not. The importance of the sulfhydryl groups was emphasized by the partial recovery of activity of the modified or oxidized enzyme (that is, treated with nitrous acid, iodine, phenyl mercuribenzoate, ferricyanide, and cupric ions) when it was treated with hydrogen sulfide or cysteine. Barley feeto-amylase (not highly purified) has been reported to contain 12—15 sulfhydryl groups per molecule by titration with p-chloromercuribenzoate, and the loss of free sulfhydryl content by treatment with L-ascorbic acid in the presence of cupric ions was found to be directly related to the loss of activity. 

One might think that since an unsaturated fatty acid is created during beta-oxidation that unsaturated fatty acids should be handled easily by this system. However two problems occur due to the high level of specificity of the enzymes involved ... 

The feeding of an EPA-free source of supplementary DHA (from algae) to human volunteers indicated a metabolic retroconversion of DHA to EPA (Conquer and Holub, 1996, 1997). Previous animal and in vitro studies in isolated rat liver cells have demonstrated that DHA can be retroconverted to EPA, and that this retroconversion is a peroxisomal function (Schlenk et al., 1969 Gronn et al., 1991). Studies in isolated rat liver cells by Schlenk et al., 1969 have also indicated that the resultant EPA can be chain-elongated to DPA (22 5n-3) for subsequent esterification into cellular lipids. An acyl-CoA oxidase has been identified as the enzyme responsible for the chain shortening of DHA in the peroxisomal beta-oxidation of PUFA in human fibroblasts (Christensen et al., 1993). The aforementioned in vivo human studies have estimated the extent of retroconversion of DHA to EPA to be approximately 10% (Conquer and Holub, 1996, 1997). 

Aoyama T, Ueno I, Kamijo T, Hashimoto T. Rat very-long-chain acyl-CoA dehydrogenase, a novel mitochondrial acyl-CoA dehydrogenase gene product, is a rate-limiting enzyme in long-chain fatty acid beta-oxidation system. cDNA and deduced amino acid sequence and distinct specificities of the cDNA-expressed protein. J Biol Chem 1994 269 19088-94. 

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