Intracellular levels and metabolism of leucine and alpha-ketoisocaproate in normal and maple syrup urine disease fibroblasts.

The interdependence of intra- and extracellular leucine and KICA concentration was studied in cultured MSUD and control fibroblasts. Intracellular KICA levels were measurable only after leucine load and were 1/20th to 1/40th that of leucine. In cells exposed to high KICA concentrations (2 mmole/liter) KICA accumulation followed linear kinetics, finally overwhelming the transamination capacity. Transamination of KICA to leucine became saturated at 2-6 mmole/liter of extracellular KICA. MSUD and control fibroblasts differed slightly in intracellular KICA concentrations, and only at high concentrations of leucine in medium. Release of KICA into the medium after leucine loading was found to be slightly increased in MSUD fibroblasts.