Carnitine acylcarnitine translocase in ischemia

摘要: The role of fatty acid oxidation as a major source energy to the contractile, working heart is well-established. However, mechanism(s) by which rates long-chain are controlled in (are) not well understood liver where lipogenic substrate, malonyl-CoA, acts switch partition acids between synthesis and degradation [1]. Early studies concluded that, at low levels pressure development, β-oxidation limited disposal acetyl-CoA through citric cycle [2]. Recent evidence from perfused, rat [3] suggests similar liver, level directly reflects changes activity tissue-specific carboxylase present cardiac myocyte. These results support view that heart, primary for malonyl-CoA regulation flux inhibition carnitine palmitoyltransferase I (CPT-I) on outer mitochondrial membrane [4]. This situation may vary, however, depending upon work load heart. When increased, increases acylcarnitine decreases acyl-CoA observed concomittent with an acceleration Since produced CPT-I must be transported across CPT-II exchange one molecule matrix, these authors suggested increase accumulation high loads limitation carnitine-dependent pathway translocase (CAT). speculation CAT exert rate-limitation under certain conditions has drawn observations diabetic ketosis [5], substrate-dependent activation [6] can up-regulate rate translocation mitochondria, respectively. In majority studies, it likely expression greatly influenced variations matrix content carnitine, latter concentrations subsaturating normal transport [5, 7]. A decrement aging [8,9] been proposed account decreased palmitoylcarnitine mitochondria 24–30 month-old rats (Table 1). related inability palmitate depress glucose extraction perfused old direct physiological consequence diminished metabolism [9]. importance further emphasized clinical cases genetic deficiencies reported (see below). functional ramifications or limiting will discussed below relation cardiac-specific effects.