Synthesis of [methyl-14C]crotonobetaine from DL-[methyl-14C]carnitine

✍ Scribed by Heinz Löster; Hermann Seim

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 311 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199602)38:2<179::aid-jlcr825>3.0.co;2-x

✦ Synopsis

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely t o be involved. Carnitine is metabolized to y-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring y-betaines -L-carnitine, crotonobetaine, y-butyrobetainelabelling with stable or radioactive isotopes became necessary.

Methyl-labelled carnitine isomers (L(-)-, D( + Ior DL-) or y-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, w e synthesized labelled crotonobetaine from labelled carnitine. Thus, DL-[methyl-l 4Clcarnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 [ZOO -400 mesh) and radient elution with hydrochloric acid. In addition to the labelled main product [methyl-B4Clcrotonobetaine (yield about 50 %I, [methyl-' 4C]glycine betaine and [methyl-l 4Clacetonyltrimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatographylautoradiography and quantified by liquid scintillation counting.