Turnover and transformation of mitochondrial acetyl-CoA acetyltransferase into CoA-modified forms

Abstract

Rat liver mitochondrial acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase, EC 2.3.1.9) exists additionally in the CoA-modified forms A1 and A2. After a pulse of radioactivity using [35S]methionine in hepatocytes, the highest radioactivity was obtained in the unmodified enzyme. Over the chase time, the radioactivity in the unmodified enzyme decreased, but simultaneously increased in both CoA-modified forms, thus proving that the fully active unmodified enzyme exists before the partially active modified forms A1 and A2. Also, the specific radioactivity (ratio % radioactivity/% immunoreactive area) of A1 > A2 demonstrates a sequential CoA modification of form A1 to form A2. Acetyl-CoA acetyltransferase was degraded with an apparent half-life of 38.0 h: the modified forms A1 and A2 have half-lives of 24.5 and 7.2 h. The physiological meaning of the CoA modification of acetyl-CoA acetyltransferase is not yet understood.