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Acyl-L-Carnitines

Introduction

Carnitine was discovered at the beginning of the last century and plays an important role in fatty acid metabolic pathways.1 It acts as a carrier of activated fatty acids across the inner mitochondrial membrane. A number of diseases caused by defects of mitochondrial transport are characterized by specific metabolic dysfunctions and depend on the physiological role of the affected carrier in intermediary metabolism.2 Therefore, the functions and roles of acyl-L-carnitines in various tissues like brain, heart and muscle continue to attract much interest.3-5

LC-MS Analysis

A prerequisite for studies on the wide variety of acyl-L-carnitines and their function is the availability of acyl-L-carnitine standards and a reliable and sensitive analytical methodology. The expansion of our acyl-L-carnitine standards has been successfully achieved by our generalized synthetic approach. Detection by MS provides the required sensitivity, and direct infusion may be sufficient to analyze a range of different acyl-L-carnitines. However, for more detailed analysis and for measuring acylcarnitine isomers, Acyl-L-Carnitines which are closely related, separation by liquid chromatography before detection is important.6-7 Liquid chromatography-mass spectrometry has therefore been established as an efficient and robust methodology for analyzing acyl-L-carnitines.8-9 Newborn screening programs detect treatable disorders in infants before they become symptomatic. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) has greatly increased the screening possibilities in newborn screening programs by monitoring levels of acylcarnitines in order to detect treatable disorders in infants before symptoms appear. LC–MS/MS can detect several disorders with a single injection, which is important in high throughput laboratories. Measuring different acylcarnitines can be used to detect more than 40 different inborn errors of metabolism, a selection of which is shown below.

Features and Benefits

  • Increasing Range of high-purity acyl-L-carnitines
  • Analytical Reagents for LC-MS analysis
  • Ascentis Express HPLC-Columns

Selected Acyl-L-carnitines for Genotype-Phenotype-Relationships in Inborn Errors of Metabolism
 

Chromosome
Gene/Locus
MIM No.
Phenotype
MIM No.
Genotypes     Phenotypes  
3p21.31 SLC25A20 613698 Carnitine-Acylcarnitine Translocase Deficiency (CACTD)
212138
1p32.3 CPT2 600650 Susceptibility to acute, infection-induced Encephalopathy (IIAE4) 614212
2p23.3 HADHA 600890 Long-chain 3-Hydroxyacyl-CoA dehydrogenase Deficiency 609016
11q25 ACAD8 604773 Isobutyryl-CoA dehydrogenase Deficiency 611283
1p31.1 ACADM 607008 Medium chain Acyl-CoA dehydrogenase Deficiency (ACADMD) 201450
8q24.3 SLC52A2 607882 Brown-Vialetto-Van Laere syndrome 2 (BVVLS2) 614707
4q32.1 ETFDH 231675 Multiple Acyl-CoA dehydrogenase Deficiency (MADD) Glutaric acidemia IIC 231680
19p13.2 CD320 606475 Methylmalonic aciduria due to transcobalamin receptor defect 613646
4q25 HADHSC 601609 Familial Hyperinsulinemic hypoglycemia 4 609975
11q13.3 CPT1A 600528 Carnitine Palmioyltransferase I Deficiency hepatic, type 1A 255120
10q26.13 ACADSB 600301 2-Methylbutyryl-CoA dehydrogenase Deficiency, 2-Methylbutyrylglycinuria 610006


LC-MS Analysis of Selected Acyl-L-Carnitines
 

Sigma-Aldrich® not only offers an expanding range of acyl-L-carnitines, but also the analytical reagents and HPLC-columns for their analysis as shown by the LC-MS of 12 homologues on an Ascentis® Express OH5 HPLC-column (2.1 × 150 mm, 2.7 μm, PN: Supelco 53764-U) with a 50 mM ammoniumformiate pH 3.0/acetonitrile-gradient at a flow rate of 0.4 mL/min. Each of the acyl-L-carnitines described below were injected with 0.1 ng on the column, while 0.2 ng of carnitine was injected.

 

Peak No. RT (min) Analyte Mol. Weight Max. m/z Cat. No.
1 6.792 Stearoyl-L-Carnitine 427.66 428.371 61229
2 6.923 Palmitoyl-L-Carnitine 399.61 400.3401 61251
3 7.078 Myristoyl-L-Carnitine 371.40 372.3091 61367
4 7.263 Lauroyl-L-Carnitine 343.50 344.2786 39953
5 7.496 Decanoyl-L-Carnitine 315.45 316.2471 50637
6 7.811 Octanoyl-L-Carnitine 287.40 288.2156 50892
7 8.295 Hexanoyl-L-Carnitine 259.30 260.1846 07439
8A 8.688 Isovaleryl-L-Carnitine 245.32 246.17 51371
8B 8.688 2-Methylbutyryl-L-Carnitine 245.32 246.17 50405
9A 9.19 Isobutyryl-L-Carnitine 231.29 232.1529 51085
9B 9.19 Butyryl-L-Carnitine 231.29 232.1529 42623
10 9.996 Propionyl-L-Carnitine 217.26 218.1375 42602
11 11.075 Acetyl-L-Carnitine HCl 203.60 204.1228 A6706
12 12.203 L-Carnitine 161.20 162.1107 C0158

 

Materials

     

 References

  1. Kerner, J.; Hoppel, C. Fatty acid import into mitochondria. Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids 1486, 1–17 (2000).
  2. Palmieri, F. Diseases caused by defects of mitochondrial carriers: A review. Biochimica et Biophysica Acta, Bioenergetics 1777, 564–578 (2008).
  3. Jones, L.L.; McDonald, D.A.; Borum, P.R. Acylcarnitines: Role in Brain. Progress in Lipid Research 49, 61–75 (2010).
  4. Calvani, M.; Reda, E.; Arrigoni-Martelli, E. Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions. Basic Research in Cardiology 95, 75–83 (2000).
  5. Muoio, D.M.; Neufer, P.D. Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle. Cell Metabolism 15, 595–605 (2012).
  6. Mansour, F.R.; Wei, W.; Danielson, N.D. Separation of carnitine and acylcarnitines in biological samples: A review. Biomedical Chromatography 27, 1339–1353 (2013).
  7. Ozben, T. Expanded newborn screening and confirmatory follow-up testing for inborn errors of metabolism detected by tandem mass spectrometry. Clinical Chemistry and Laboratory Medicine 51, 157–176 (2013).
  8. Lehotay, D.C.; Hall, P.; Lepage, J.; Eichhorst, J.C.; Etter, M.L.; Greenberg, C.R. LC–MS/MS progress in newborn screening. Clinical Biochemistry 44, 21–31 (2011).
  9. Minzhi, P.; Xiefan, F.; Yonglan, H.; Yanna, C.; Cuili, L.; Ruizhu, L.; Li, L. Separation and identification of underivatized plasma acylcarnitine isomers using liquid chromatography–tandem mass spectrometry for the differential diagnosis of organic acidemias and fatty acid oxidation defects. J. Chromatography A 1319, 97–106 (2013).

 

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