3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase

Wulf Röschinger; David S. Millington; Douglas A. Gage; Zhi H. Huang; Takeo Iwamoto; Shoji Yano; Seymour Packman; Kay Johnston; Susan A Berry; Lawrence Sweetman

doi:10.1016/0009-8981(95)06126-2

3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase

Wulf Röschinger, David S. Millington, Douglas A. Gage, Zhi H. Huang, Takeo Iwamoto, Shoji Yano, Seymour Packman, Kay Johnston, Susan A Berry, Lawrence Sweetman

Pediatric Genetics & Metabolism

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	35-51
Number of pages	17
Journal	Clinica Chimica Acta
Volume	240
Issue number	1
DOIs	https://doi.org/10.1016/0009-8981(95)06126-2
State	Published - Aug 31 1995

Bibliographical note

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.

Keywords

3-Hydroxyisovalerylcamitine
3-Methylcrotonyl CoA carboxylase
Acylcamitine

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10.1016/0009-8981(95)06126-2

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@article{9ae2cca972d541bd84207030e3a97d1a,

title = "3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase",

abstract = "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.",

keywords = "3-Hydroxyisovalerylcamitine, 3-Methylcrotonyl CoA carboxylase, Acylcamitine",

author = "Wulf R{\"o}schinger and Millington, {David S.} and Gage, {Douglas A.} and Huang, {Zhi H.} and Takeo Iwamoto and Shoji Yano and Seymour Packman and Kay Johnston and Berry, {Susan A} and Lawrence Sweetman",

note = "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.",

year = "1995",

month = aug,

day = "31",

doi = "10.1016/0009-8981(95)06126-2",

language = "English (US)",

volume = "240",

pages = "35--51",

journal = "Clinica Chimica Acta",

issn = "0009-8981",

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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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VL - 240

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JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

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ER -

3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase

Abstract

Bibliographical note

Keywords

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