Metabolic response to carnitine in methylmalonic aciduria. An effective strategy for elimination of propionyl groups.

Journal Article (Journal Article)

Patients with methylmalonic aciduria have an excessive intramitochondrial accumulation of acylcoenzyme A compounds that may reduce the availability of free coenzyme A (CoA) for normal metabolic requirements, producing profound metabolic disturbances. Giving carnitine to a patient with methylmalonic aciduria produced an increase in hippurate excretion (an index of intramitochondrial adenosine triphosphate (ATP) and CoA availability), a large increase in short chain urinary acylcarnitines, and a reduction in excretion of methylmalonate and methylcitrate. These acylcarnitines were shown by fast atom bombardment and B/E linked scan mass spectrometry to be propionylcarnitine and acetylcarnitine. Carnitine acts by removing (detoxifying) propionyl groups, thereby releasing CoA and restoring ATP biosynthesis and concentrations towards normal. L-carnitine may play a central role in maintenance of mitochondrial and cellular homoeostasis in methylmalonic aciduria and propionic acidaemia. These principles may provide an approach to the treatment of this and other disorders, inherited and acquired, in which accumulation of acyl CoA metabolites results in sequestration of free CoA, thereby perturbing metabolic homoeostasis.

Full Text

Duke Authors

Cited Authors

  • Roe, CR; Hoppel, CL; Stacey, TE; Chalmers, RA; Tracey, BM; Millington, DS

Published Date

  • November 1, 1983

Published In

Volume / Issue

  • 58 / 11

Start / End Page

  • 916 - 920

PubMed ID

  • 6651329

Pubmed Central ID

  • PMC1628370

Electronic International Standard Serial Number (EISSN)

  • 1468-2044

Digital Object Identifier (DOI)

  • 10.1136/adc.58.11.916


  • eng

Conference Location

  • England