Preserving mitochondrial function prevents the proteasomal degradation of GTP cyclohydrolase I

► Acetyl-l-carnitine attenuated ADMA-mediated proteasomal degradation of GTP cyclohydrolase I (GCH1). ► This prevented the decrease in BH4 levels. ► Treatment of Shunt lambs with l-carnitine also reduced the degradation of GCH1. ► This increased the BH4 levels compared to vehicle-treated Shunt lambs. ► Increases in BH4 enhanced NO generation in Shunt lambs.