Oxidation fatty adds

Some fatty add oxidation occurs but its quantitative significance is not known. 

Gregersen N, Andresen BS, Corydon MJ, Gorydon TJ, Olsen RK, Bolund L, Bross P. Mutation analysis in mitochondrial fatty add oxidation defects Exemplified by acyl-CoA dehydrogenase defidendes, with spedal focus on genotype-phenotype relationship. Hum Mutat. 2001 Sep 18(3) 169-89. Review. PubMed dtation... 

In mitochondria, there are four fatty acyl CoA dehydrogenase species, each of which has a specificity for either short-, mediurr-long-, or very-long-chain fatty acids. MCAD deficiency, an autos mal, recessive disorder, is one of the most common inborn errors of metabolism, and the most common inborn error of fatty add oxidation, being found in 1 in 12,000 births in the west, and 1 in 40,000 worldwide. It causes a decrease in fatty acid oxidation and severe hypoglycemia (because the tissues cannot obtain full ener getic benefit from fatty acids and, therefore, must now rely on glu cose). Treatment includes a carbohydrate-rich diet. [Note Infants are particularly affected by MCAD deficiency, because they rely for their nourishment on milk, which contains primarily MCADs. 

I. F. Hutter, H. M, Piper, and P. G Spieckennann. Myocardial fatty add oxidation Evidence for an albumin receptor mediated membrane transfer of fatty adds. Basic... 

The study reported in Table 4.12 illustrates the role of carnitine in fatty add oxidation and introduces the topic of medium-chain fatty acids. This study, conducted before the role of carnitine in fatty acid transport was realized, involved addition of radioactive fatly acids to suspensions of liver mitochondria. The fatty acids used iriduded [ "Cjoctanoic acid (medium-chain) and [ " Clpalmitic add (long-chain). The susperisions were incubated for 30 minutes to permit uptake of the fatty acids, their subsequent oxidation, and discharge of radioactive carbon dioxide. The produced in the Krebs cycle diffuses out of the mitochondria into the surrounding fluid-... 

The cycle of reactions resulting in the discharge of a two-carbon unit from a fatty add as acetyl-Co A produces no CO2 and the equivalent of 2 H2. These 2 H2 can be used for the reduction of one molecule of oxygen. Hence, activation of the fatty acid oxidation pathway in a tissue or animal would be expected to result in a decrease in the RQ for the organism. The breakdown of fatty adds followed by the oxidation of acetyl-CoA in the Krebs cycle results in the production of 2CO2 and the consumption of 3 O2. Thus, the RQ for an organ or animal rel)dng primarily on fatty add oxidation as an energy source would be expected to be 2.0/3.0, or 0.66. The RQ for fat is about 0.66. 

Adiponectin Peptide oligomers of Muscle Increases fatty add oxidation... 

Figure 55-3 Protocol for the postmortem screening of FAO disorders. (From Rinaldo Matern D, Bennett MJ. Fatty add oxidation disorders. Ann Rev Physiol 2002 64 477-502.)...

Selected fatty add oxidation disorders are discussed in the following sections. 

The isovaleryl CoA derived from leucine is dehydrogenated to yield /B-methylcrotonyl CoA. This oxidation is catalyzed by isovaleryl CoA dehydrogenase. The hydrogen acceptor is FAD, as in the analogous reaction in fatty add oxidation that is catalyzed by acyl CoA dehydrogenase. -Methylglutaconyl CoA is then formed by the carboxylation of 3-methylcrotonyl CoA at the expense of the hydrolysis of a molecule of ATR As might be expected, the carboxylation mechanism of p-methylcrotonyl CoA carboxylase is similar to that of pyruvate carboxylase and acetyl CoA carboxylase. 

Acetyl (/oA, NADH, and FADH Are Generated in Each Round of Fatty Add Oxidation... 

Gregersen N, Andresen BS, Bross P. Prevalent mutations in fatty add oxidation disorders diagnostic considerations. Eur J Pediatr. 2000 Dec 159 Suppl 3 S213-8. Review. PubMed citation... 

See also / -Oxidation of Saturated Fatty Add Unsaturated Fatty Add Oxidation, Oxidation of Odd-Numbered Fatty Acids, Peroxisomal / -Oxidation, Fatty Acids... 

Metals can initiate fatty add oxidation by reaction with oxygen. The anion thus produced can either lose an electron to give singlet oxygen or react with a proton to form a peroxyl radical, which serves as a good chain initiator (Reaction 12.11). 

By contrast to CPT 11 which has been found as one isoform, mammalian tissues express two isoforms of CPT 1, the liver (L-CPT p and the muscle (M-CPT 1) forms, that are approximately 62% identical in amino acid sequence. The liver isoform is present in the mitochondria of liver, pancreas, kidney, brain and most other tissues, while M-CPT 1 is the isoform expressed in skeletal muscle as well as in white and brown adipocytes. L-CPT 1 is highly expressed in the fetal heart, but its expression decreases after birth with a concomitant increase in the expression of the M-CPT I. Unlike L-CPT I which displays altered sensitivity to malonyl-CoA under different physiopatho-logical conditions," M-CPT I is very sensitive to malonyl-CoA inhibition but does not undergo any alteration of its sensitivity to malonyl-CoA. The concentration of malonyl-CoA is much lower in heart than in rat hver, but it is sufficient to inhibit fatty add oxidation. The important question in cardiac metabolism, which is still unsolved, is how can fatty acid oxidation proceed in the presence of malonyl-CoA ... 

Stephens, T.W., Higgins, A.J., Cook, G.A. Harris, R.A. (1985) Two mechanisms produce tissue-specific inhibition of fatty add oxidation by oxfenicine. Biochem. J. IVt, 651-660. 

Molecular MechanisiiK of Fatty Add -Oxidation Enxyme Catafyds... 

Introduction of methyl groups to fatty adds makes them more inert to fatty add oxidation. Recently, we have syndiesized several methyl- or ethyl-derivatives of EPA, to make them more inert to fatty add oxidation than EPA itself Fatty acids that are difficult to metabolize are well known to increase the fatty acid oxidation, in addition to lowering plasma lipids, and the EPA-derivatives are therefore expected to influence the fatty acid oxidation system. However, different d rees of methylation, and the localization of the methyl group on EPA could have importance for the effects on lipid metabolism and plasma lipid level, and this was studied. 

We measured the activity of some enzymes involved in lipogenesis, that is, acetyl-CoA carboxylase, the rate-limiting enzyme in fatty add synthesis, and fatty acid synthase, another enzyme in fatty acid synthesis. The activities of Aese eni mes seemed to decrease after administration of the same EPA-derivatives as were found to increase the fatty add oxidation. 

Interestingly, fatty add oxidation studies in fibroblasts from our patient revealed deficient oxidation of both straight-chain as well as 2-methyl-branched fatty acids (C26 0 and pristanic acid, respectively). These data suggest that the D-bifimctional protein may also be the primary hydratase/dehydrogenase involved in C26 0 p-oxidation. This is now under active study. 

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