Beta-Oxidation cycle

Goepfeit S, Vidoudez C, Rezzonico E, HUtunen JK, Poirier Y (2005) Molecular identification and characterization of the Arabidopsis Delta(3, 5), Delta (2, 4)-dienoyl-coenzyme A isomerase, a peroxisomal enzyme participating in the beta-oxidation cycle of unsaturated fatty acids. Plant Physiol 138 1947-1956... 

Mitochondria. These are intracellular structures, producing the bulk of cell energy. They oxidize glucose-derived pyruvate, keto-acids and fatty acids in the tricarboxylic and beta oxidation cycles, respectively. These pathways are coupled with the oxidative phosphorylation chain in which ATP is synthesized. Neuronal mitochondria do not utilize fatty acids. They almost exclusively utilize glucose or lactate and sometimes keto-acids. 

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. 

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... 

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. 

Ventura FV, Ijlst L, Ruiter J, Ofman R, Costa CG, Jakobs C, Duran M, Tavares de Almeida I, Bieber LL, Wanders RJ. Carnitine palmitoyltransferase II specificity towards beta-oxidation intermediates-evidence for a reverse carnitine cycle in mitochondria. Eur. J. Biochem. 1998 253 614-618. 

Fatty acids undergo beta oxidation in the liver and form acetyl CoA. If acetyl CoA accumulates instead of traversing the citric-acid cycle, the liver becomes more dependent on beta oxidation than on the citric-acid cycle for its source of high-energy phosphate. To continue beta oxidation, coenzyme A is required. If all the CoA is tied up as fatty-acyl CoA and acetyl CoA, no beta oxidation occurs. However, there is a metabolic pathway, unique to the liver, through which to overcome this apparent dilemmaketone-body formation (Fig. 14.3). It occurs as follows in the mitochondrial matrix. 

The liver is the main origin of ketones in laboratory animals, where the long chain fatty acids are released from plasma albumin and bound to fatty acid-binding proteins in the hepatocytes. The long chain fatty acids react with CoA and then can be used to synthesize triacylglycerol or undergo beta-oxidation to acetyl CoA. When the levels of plasma fatty acids are elevated, acetyl CoA can be metabolized to form acetoacetate and 3-hydroxybutyrate or enter the tricarboxylic acid cycle. In ketosis, the levels of acetone, acetoacetate, and 3-hydroxybutyrate (also known as beta-hydroxybutyrate) are increased in both plasma and urine these three compounds historically were collectively called ketone bodies. Urine test strips can be used to test for ketonuria, and there are several enzymatic assays for 3-hydroxybutyrate and acetoacetate. 

Beta-oxidation The major metaboiic pathway for oxidising fatty acids, so-caiied because in each cycle it is at the beta-carbon (two along from the carboxyl group linked to CoA) where oxidation occurs. 

Reichmann, H. DeVivo, D.C. (1991) Comp. Biochem. Physiol. 98R 327-331. Coordinate enzymatic activity of beta-oxidation and purine nucleotide cycle in a diversity of muscle and other organs of rat. Melde, K., Jackson, S., Bartlett, K., Sherratt, H.S.A. Ghisla, S. 99 )Biochem. J. 274,395-400. Metabolic consequences of methylenecyclopropylglycine poisoning in rats. 

One of the functions of hepatic P-oxidation is to provide ketone bodies, acetoac-etate and p-hydroxybutyrate, to the peripheral circulation. These can then be utilized by peripheral tissues such as brain and heart. Beta-oxidation itself produces acetyl-CoA which then has three possible fates entry to the Krebs cycle via citrate S5mthase keto-genesis or transesterification to acetyl-carnitine by the action of carnitine acetyltrans-ferase (CAT). Intramitochondrial acetyl-carnitine then equilibrates with plasma via the carnitine acyl-camitine translocase and presumably via the plasma membrane carnitine transporter. Human studies have shown that acetyl-carnitine may provide up to 5% of the circulating carbon product from fatty acids and can be taker and utilized by muscle and possibly brain." In addition, acyl-camitines are of important with regard to the diagnosis of inborn errors of P- oxidation. For these reasons, we wished to examine the production of acetyl-carnitine and other acyl-camitine esters by neonatal rat hepatocytes. 

Moire L, Rezzonico E, Goepfert S, Poirier Y (2004) Impact of unusual fatty add synthesis on futile cycling through beta-oxidation and on gene expression in transgenic plants(l[w]). Plant Physiol 134 432-442... 

The catabolism of fatty acids occurs in the mitochondria through a systematic process called beta-oxidation, whereby 2-carbon fragments are successively chopped from the fatty acid molecule to form acetyl CoA which then enters the Krebs cycle. The term lipolysis indicates mobilization of fats... 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

Welsh, N., Eizirik, D. L., Bendtzen, K., and Sandler, S. (1991). lnterleukin-1 beta-induced nitric oxide production in isolated rat pancreatic islets requires gene transcription and may lead to inhibition of the Krebs cycle enzyme aconitase. Endocrinology (Baltimore) 129, 3167-3173. 

To better understand the Sn-beta chemistry, a detailed experimental investigation into the mechanism of the BV oxidation was conducted (68). It was estabhshed by IR spectroscopy that the catalytic cycle starts with the... 

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