TY - JOUR
T1 - 3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase
AU - Röschinger, Wulf
AU - Millington, David S.
AU - Gage, Douglas A.
AU - Huang, Zhi H.
AU - Iwamoto, Takeo
AU - Yano, Shoji
AU - Packman, Seymour
AU - Johnston, Kay
AU - Berry, Susan A.
AU - Sweetman, Lawrence
N1 - Funding Information:
W.R. was supportedb y the DeutscheF orschungsgemcinsch(aRfot 763/1-2), whichi s gratefullya cknowledgeSdo. meo f the masss pectradl ataw crca cquireda t the MSU-NIH Mass SpectrometrFya cilityw hichi s supportedin, part, by a grant (RR00480f)r om the NationalI nstituteso f Health,N ationalC enterf or Research Resources.
PY - 1995/8/31
Y1 - 1995/8/31
N2 - Highly elevated urinary acylcamitine levels (range: 27.1-1314.0; normal: <30 mmol/mol creatinine) combined with a generalized, severe decrease of free carnitine before treatment in six patients of two families with an isolated biotin-unresponsive deficiency of 3-methylcrotonyl CoA:carboxylase (3-methylcrotonyl-CoA:carbon dioxide ligase; EC 6.4.1.4) prompted the study to specify the acyl moities attached to the carrier molecule carnitine. Only traces of 3-methylcrotonyl carnitine (1.3-2.2% of total ester concentration) were found by high performance liquid chromatography, whereas the prominent species determined by fast-atom bombardment/tandem mass spectrometry and gas chromatography-mass spectrometry corresponded to a hydroxy five-carbon-acylcamitine. Crude urine samples were derivatized directly and the resulting N-demethylcamitine-propylester and trimethylsilylesters/ethers of intact acylcarnitines analyzed by gas chromatography-mass spectrometry. Mass spectra acquired by both chemical ionization and electron impact gave both the molecular weight and fragmentation patterns consistent with that expected for 3-hydroxyisovaleryl carnitine. In addition, acylcarnitines were extracted from urine, hydrolyzed and the trimethylsilyl-derivatives of the organic acids analyzed by gas chromatography-mass spectrometry. Free 3-hydroxyisovaleric acid found in the hydrolyzed sample and not in an unhydrolyzed one confirmed the suggested acyl group.
AB - Highly elevated urinary acylcamitine levels (range: 27.1-1314.0; normal: <30 mmol/mol creatinine) combined with a generalized, severe decrease of free carnitine before treatment in six patients of two families with an isolated biotin-unresponsive deficiency of 3-methylcrotonyl CoA:carboxylase (3-methylcrotonyl-CoA:carbon dioxide ligase; EC 6.4.1.4) prompted the study to specify the acyl moities attached to the carrier molecule carnitine. Only traces of 3-methylcrotonyl carnitine (1.3-2.2% of total ester concentration) were found by high performance liquid chromatography, whereas the prominent species determined by fast-atom bombardment/tandem mass spectrometry and gas chromatography-mass spectrometry corresponded to a hydroxy five-carbon-acylcamitine. Crude urine samples were derivatized directly and the resulting N-demethylcamitine-propylester and trimethylsilylesters/ethers of intact acylcarnitines analyzed by gas chromatography-mass spectrometry. Mass spectra acquired by both chemical ionization and electron impact gave both the molecular weight and fragmentation patterns consistent with that expected for 3-hydroxyisovaleryl carnitine. In addition, acylcarnitines were extracted from urine, hydrolyzed and the trimethylsilyl-derivatives of the organic acids analyzed by gas chromatography-mass spectrometry. Free 3-hydroxyisovaleric acid found in the hydrolyzed sample and not in an unhydrolyzed one confirmed the suggested acyl group.
KW - 3-Hydroxyisovalerylcamitine
KW - 3-Methylcrotonyl CoA carboxylase
KW - Acylcamitine
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U2 - 10.1016/0009-8981(95)06126-2
DO - 10.1016/0009-8981(95)06126-2
M3 - Article
C2 - 8582058
AN - SCOPUS:0029119524
SN - 0009-8981
VL - 240
SP - 35
EP - 51
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1
ER -