Abstract
A rat liver acetyl-coenzyme A hydrolase, which appears to have an extra-mitochondrial location, has escaped previous detection presumably due to its extreme cold lability and to its ATP-sensitivity. This enzyme activity is highly regulated by nucleotides. The enzyme is activated by ATP and completely in-hibited by ADP and has various forms (tetramer, dimer and monomer). In the presence of ATP or ADP, but not AMP, at room temperature, the dimeric form (Mr 135,000) of the enzyme reassociates to the tetrameric form (Mr 240,000) and removal of nucleotides from the tetrameric enzyme causes its dissociation, mainly into the enzymatically active dimeric form and partly into the inactive monomer. Formation of the monomer is greater whetn the dimeric and tetrameric forms are treated at low temperature. ATP (2mM), phosphate (0.9M) and pyrophosphate (0.45M) enhance reactivation of the enzyme on rewarming, judged by recovery of catalytic activity and restoration of dimer and tetramer forms. The apparent Km values for acetyl-CoA of the dimeric and tetrameric forms are different, being 170μM and 60μM, respectively. Increase in cytosolic acetyl-CoA hydrolase activity was observed in opposite metabolic states: namely, during fatty acid oxidation (hypolipidemic acid administration, starvation and diabetes) and during fatty acid synthesis (refeeding on fat-free diet with a high carbohydrate content with or without 1% thyroid powder). Thus the enzyme activity may change in response or adaptation to unusual physiological states. Increase in cytosolic acetyl-CoA hydrolase, which hydrolyzes acetyl-CoA to CoASH and acetate, can be interpreted as an effective method for regulating the cytosolic acetyl-CoA and cytosolic free CoASH concentration, which is known to be important in both lipogenesis and lipolysis.
