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Fatty acid oxidation carnitine esters

Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ... Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ...
Schmidt-Sommerfeld E, Bobrowski PJ, Penn D, Rhead WJ, Wanders RJA, Bennet MJ (1998) Analysis of carnitine esters by radio-high performance liquid chromatography in cultured skin fibroblasts from patients with mitochondrial fatty acid oxidation disorders. Pediatr Res 44 210-214... [Pg.204]

Figure 9-1- Role of carnitine in fatty acid oxidation. Long-chain fatty acids are activated as the thioester of CoA on the cytoplasmic side of the mitochondrial membrane. The fatty acyl group is then transferred to form the corresponding carnitine ester in a reaction catalyzed by carnitine palmitoyltransferase I (CPT ]) The acylcarnitine then enters the mitochondrial matrix in exchange for carnitine via the carnitine-acylcarnitine translocase. The acyl group is transferred back to CoA in the matrix by carnitine palmitoyltransferase II (CPT II). The intramitochondrial acyl-CoA can then undergo P-oxidation. Figure 9-1- Role of carnitine in fatty acid oxidation. Long-chain fatty acids are activated as the thioester of CoA on the cytoplasmic side of the mitochondrial membrane. The fatty acyl group is then transferred to form the corresponding carnitine ester in a reaction catalyzed by carnitine palmitoyltransferase I (CPT ]) The acylcarnitine then enters the mitochondrial matrix in exchange for carnitine via the carnitine-acylcarnitine translocase. The acyl group is transferred back to CoA in the matrix by carnitine palmitoyltransferase II (CPT II). The intramitochondrial acyl-CoA can then undergo P-oxidation.
These findings are consistent with impaired fatty-acid oxidation reduced mitochondrial entry of long-chain acylcarnitine esters due to inhibition of the transport protein (carnitine palmityl transferase 1) and failure of the respiratory chain at complex II. Another previously reported abnormality of the respiratory chain in propofol-infusion syndrome is a reduction in cytochrome C oxidase activity, with reduced complex IV activity and a reduced cytochrome oxidase ratio of 0.004. Propofol can also impair the mitochondrial electron transport system in isolated heart preparations. [Pg.2951]

Oleate is an abundant 18-carbon monounsaturated fatty acid with a cis double bond between C-9 and C-10 (denoted A ). In the first step of oxidation, oleate is converted to oleoyl-CoA and, like the saturated fatty acids, enters the mitochondrial matrix via the carnitine shuttle (Fig. 17-6). Oleoyl-CoA then undergoes three passes through the fatty acid oxidation cycle to yield three molecules of acetyl-CoA and the coenzyme A ester of a A, 12-carbon unsaturated fatty acid, cis-A -dodecenoyl-CoA (Fig. 17-9). This product cannot serve as a substrate for enoyl-CoA hydratase, which acts only on trans double bonds. The auxiliary enzyme A, A -enoyl-CoA isomerase isomerizes the ci5-A -enoyl-CoA to the fra/J5-A -enoyl-CoA, which is converted by enoyl-CoA hydratase into the corresponding L-/3-hydroxyacyl-CoA (fra/75-A -dodecenoyl-CoA). This intermediate is now acted upon by the remaining enzymes of /3 oxidation to yield acetyl-CoA and the coenzyme A ester of a 10-carbon saturated fatty acid, decanoyl-CoA. The latter undergoes four more passes through the pathway to yield five more molecules of acetyl-CoA. Altogether, nine acetyl-CoAs are produced from one molecule of the 18-carbon oleate. [Pg.641]

Carnitine acyltransferases (CATs) are a family of enzymes that transport fatty acyl-CoAs across membranes in a range of organelles so that the CoA-esters can be met -olized further. The CAT enzyme involved depends on the lengfli of the fatty acid moeity to be transported. Carnitine acetyltransferase acts with acetyl-CoA as substrate while mitochondrial carnitine palmitoyltransferase (CPT) I and CPT D, transport long-chain acyl groups into the mitochondrial matrix, where they undergo -oxidation. Peroxisomal carnitine octanoyltransferase (COT) transports medium-chain fatty acids across the membrane in peroxisomes in a similar way to CPT I in mitochondria. Peroxisomal P-oxi-dation may account for a significant proportion of all hver fatty acid oxidation and COT is involved in this process. ... [Pg.96]

To get further support for the idea that the peroxisomes are involved in the metabolism of these fatty acids we tested the effect of )-decanoylcamitine. This is the unphysiological isomer of the carnitine ester which inhibits the carnitine-dependent mitochondrial fatty acid oxidation, while it has no effect on the carnitine-independent fatty acid oxidation in the peroxisomes. [Pg.101]

The initial formation of palmitylcarnitine occurs external to the membrane barrier to palmityl-CoA (reaction 1). Once transport has been effected, the palmitylcarnitine is reconverted to the coenz3nne A ester (reaction 2). The reaction catalyzed by palmitylcarnitine transferase is an equilibrium reaction so that under normal circumstances if oxidation is taking place the conversion of extra mitochondrial palmityl-CoA to palmityl carnitine does not become rate limiting for fatty acid oxidation. However, the situation during development is quite different and the generation of palmitylcarnitine external to the mitochondrial membrane barrier may impose constraints on fatty acid oxidation. [Pg.91]

Mitochondria contain all the enzymes necessary for oxidation of fatty acids but, before this can take place, the fatty acids have to be transported into the mitochondria. Transport requires the formation of an ester of the fatty acid with a compound, carnitine, in a reaction catalysed by the enzyme carnitine palmitoyltransferase ... [Pg.134]

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. [Pg.636]

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. [Pg.270]

Carititine (3-hydroxy,4-AT-trimethylaminobutyric acid) has a central role in the transport of fatty acids across the mitochondrial membrane for p -oxidation. At the outer face of the outer mitochondrial membrane, carnitine acyltransferase I catalyzes the reaction shown in Figure 14.1, the transfer of fatty acids from coenzyme A (CoA) to form acyl carnitine esters that cross into the mitochondrial matrix. At the timer face of the inner mitochondrial membrane, carnitine acyltransferase II catalyzes the reverse reaction. [Pg.385]


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Carnitin

Carnitine

Esters oxidation

Fatty acids esters

Fatty acids oxidation

Oxidized fatty acids

Oxidized fatty esters

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