InChI=1S/C35H60N7O17P3S/c1- 4- 5- 6- 7- 8- 9- 10- 11- 12- 13- 14- 15- 26(44) 63- 19- 18- 37- 25(43) 16- 17- 38- 33(47) 30(46) 35(2,3) 21- 56- 62(53,54) 59- 61(51,52) 55- 20- 24- 29(58- 60(48,49) 50) 28(45) 34(57- 24) 42- 23- 41- 27- 31(36) 39- 22- 40- 32(27) 42/h11- 12,22- 24,28- 30,34,45- 46H,4- 10,13- 21H2,1- 3H3,(H,37,43) (H,38,47) (H,51,52) (H,53,54) (H2,36,39,40) (H2,48,49,50) /p- 4/b12- 11- /t24- ,28- ,29- ,30+,34- /m1/s1 |
MRVDZOHJMLTLHJ-STFCKWFXSA-J |
CCCCCCCC\C=C/CCCC(=O) SCCNC(=O) CCNC(=O) [C@H] (O) C(C) (C) COP([O- ] ) (=O) OP([O- ] ) (=O) OC[C@H] 1O[C@H] ([C@H] (O) [C@@H] 1OP([O- ] ) ([O- ] ) =O) n1cnc2c(N) ncnc12 |
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(5Z)-tetradecenoyl-CoA
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UniProt
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(5Z)-tetradecenoyl-coenzyme A(4−)
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ChEBI
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Violante S, Ijlst L, van Lenthe H, de Almeida IT, Wanders RJ, Ventura FV (2010) Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. Biochimica et biophysica acta 1802, 728-732 (Source: SUBMITTER) [PubMed:20538056] [show Abstract] Over the last years acylcarnitines have emerged as important biomarkers for the diagnosis of mitochondrial fatty acid beta-oxidation (mFAO) and branched-chain amino acid oxidation disorders assuming they reflect the potentially toxic acyl-CoA species, accumulating intramitochondrially upstream of the enzyme block. However, the origin of these intermediates still remains poorly understood. A possibility exists that carnitine palmitoyltransferase 2 (CPT2), member of the carnitine shuttle, is involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites. To address this issue, the substrate specificity profile of CPT2 was herein investigated. Saccharomyces cerevisiae homogenates expressing human CPT2 were incubated with saturated and unsaturated C2-C26 acyl-CoAs and branched-chain amino acid oxidation intermediates. The produced acylcarnitines were quantified by ESI-MS/MS. We show that CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters, whereas virtually no activity was found with short- and very long-chain acyl-CoAs or with branched-chain amino acid oxidation intermediates. Trans-2-enoyl-CoA intermediates were also found to be poor substrates for CPT2. Inhibition studies performed revealed that trans-2-C16:1-CoA may act as a competitive inhibitor of CPT2 (K(i) of 18.8 microM). The results obtained clearly demonstrate that CPT2 is able to reverse its physiological mechanism for medium and long-chain acyl-CoAs contributing to the abnormal acylcarnitines profiles characteristic of most mFAO disorders. The finding that trans-2-enoyl-CoAs are poorly handled by CPT2 may explain the absence of trans-2-enoyl-carnitines in the profiles of mitochondrial trifunctional protein deficient patients, the only defect where they accumulate, and the discrepancy between the clinical features of this and other long-chain mFAO disorders such as very long-chain acyl-CoA dehydrogenase deficiency. |
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