Long-chain fatty acids oxidation

Pollitt, R. J., 1995. Disorders of mitochondrial long-chain fatty acid oxidation. Journal of Inherited Metabolic Disease 18 473—490. 

Figure22-10. Regulation of long-chain fatty acid oxidation in the liver. (FFA, free fatty acids VLDL, very low density lipoprotein.) Positive ( ) and negative ( ) regulatory effects are represented by broken arrows and substrate flow by solid arrows.

Browning MF, Larson C, Strauss A, Marsden DL (2005) Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects. J Inherit Metab Dis 28 545-550... 

Roe DS, Yang BZ, Vianey-Saban C, Struys E, Sweetman L, Roe CR (2006) Differentiation of long-chain fatty acid oxidation disorders using alternative precursors and acylcarnitine profiling in fibroblasts. Mol Genet Metab 87 40-47... 

In contrast to the general peroxisome biogenesis defects, patients with X-linked adrenoleucodystrophy, whose very-long-chain fatty acid oxidation is impaired as a result of an uptake defect, show minimal abnormalities of their DHA levels. 

A deficiency of very long-chain fatty acid oxidation in peroxisomes is apparently caused by a defective transporter of the ABC type (Chapter 8).55 The disease, X-linked adrenoleukodystrophy (ALD), has received considerable publicity because of attempts to treat it with "Lorenzo s oil," a mixture of triglycerides of oleic and the C22 monoenoic erucic acid. The hope has... 

Sun T. Xu, Z. Godber, J.S. Prinyawiwatkul, W. 2006. Capabilities of oat extraets in inhibiting eholesterol and long chain fatty acid oxidation during heating. Cereal Chem. 83 451-454. 

Fritz, L B. (1959). Action of carnitine on long chain fatty acid oxidation by liver. Am. /. Pfitfsiol. 197, 297-304. 

The answer is c. (Murray, pp 307—346. Scriver, pp 1909-1964. Sack, pp 121-138. Wilson, pp 287-317.) The steps of the urea cycle are divided between the mitochondrial matrix and cytosol of liver cells in mammals. The formation of ammonia, its reaction with carbon dioxide to produce carbamoyl phosphate, and the conversion to citrulline occur in the matrix of mitochondria. Citrulline diffuses out of the mitochondria, and the next three steps of the cycle, which result in the formation of urea, all take place in the cytosol. Peroxisomes have single membranes, in contrast to the double membranes of mitochondria. They house catalase and enzymes for medium- to long-chain fatty acid oxidation. 

The inhibition of CPT I by either POCA or MeTDGA caused a decrease in [ l4C]palmitate oxidation. MeTDGA effectively inhibited palmitate oxidation in kidney cortex slices [98], diaphragm [98], heart [99] and hepatocytes [ 100] from fasted rats. POCA produced an almost complete suppression of long-chain fatty acid oxidation in the perfused rat heart from either fed or fasted animals [101]. POCA also inhibited hepatocyte oxidation of oleate up to 85% with maximal effects of POCA observed at concentrations as low as 1 /xM... 

THE USE OF [9,10- MYMSTATE, [9,10- H]PALMITATE AND [9,10- ]OLEATE FOR THE DETECTION AND DIAGNOSIS OF MEDIUM AND LONG-CHAIN FATTY ACID OXIDATION DISORDERS IN INTACT CULTURED FIBROBLASTS... 

The Detection and Diagnosis of Medium and Long-Chain Fatty Acid Oxidation Disorders... 

Figure 5. The data show how patients with confirmed or suspected defects of the mitochondrial respiratory chain can be separated from patients with confirmed long chain fatty acid oxidation defects (data from Figure 4 plus 8 cases of LCHAD). In each case the release of H O from [9,10- H)myristate, [9,10- H]palmitate and [9,10- H]oleate was determined in parallel with at least 3 unaffected cell lines (not all control data plotted). All determinations were in duplicate and the activities for the individual cell lines are expressed as a proportion of the assay mean.

Olpin, S.E., Manning, N.J., Pollitt, R.J. Clark, S. (1997). J. Inherited Metab. Dis. 20, 415-419. Improved detection of long-chain fatty acid oxidation defects in intact cells using [9,10- H]oleate. Vianey-Saban, C., Divry, C., Brivet, M., Nada, M., Zabot, M.T., Mathieu, M. Roe, C. (1998) Clin. Chim. Acta, 269, 43-62. Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase deficiency clinical characteristics and diagnostic considerations in 30 patients. 

Biochemical studies in fibroblasts from the index patient showed that the rate of P-oxidation of myristate and palmitate was severely decreased to less than 5% of the controls (Table 1). Enzyme measurements of the very-long chain acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, thiolase, carnitine palmitoyltransferase I and II showed normal activities (not shown). The severe deficiency of long chain fatty acid oxidation was explained by the complete deficiency of CAC activity (Table 1). 

L-camitine is given in many metabohc disorders as a supplement or to correct a carnitine deficiency. The dose of carnitine can vary between 50 and 100 mg/kg/day, and in some organic acidurias, as much as 200-300 mg/kg/24 days may be necessary, hi some of the long-chain fatty acid oxidation disorders, use of carnitine is controversial, and in the view of potential adverse effects (formation of car-diotoxic acylcamitines), supplementation at time of metabolic decompensation should be avoided [18]. 

Symptoms of cardiac or skeletal muscle dysfunction pose problems, particularly for patients with long-chain fatty acid oxidation disorders. 

Behrend AM, Harding CO, Shoemaker JD, Matern D, Sahn DJ, Elliot DL, et al. Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation. Mol Genet Metab. 2012 105(l) 110-5. PubMed PMID 22030098, Pubmed Central PMCID 3253922. 

Box 24.1 Principles of Dietary Treatment of Long-Chain Fatty Acid Oxidation Defects... 

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