The short-term regulation of hepatic acetyl-CoA carboxylase during starvation and re-feeding in the rat.
Rapid inhibition of acetyl-CoA carboxylase (ACC) activity in rat liver in response to 6 h starvation and rapid re-activation in response to 2-6 h of re-feeding chow were shown to be due to changes in the expressed activity of existing enzyme. Decreases and increases in ACC concentration occurred at later stages of the transitions, i.e. 6-48 h starvation and 8-24 h re-feeding respectively. The decrease in expressed activity of ACC was due primarily to changes in its phosphorylation state, demonstrated by a significantly decreased Vmax. and significantly increased Ka for citrate of enzyme purified by avidin-Sepharose chromatography from 6 h- or 48 h-starved rats. These effects were totally reversed within 2-4 h of chow re-feeding. Changes in the activity of purified ACC closely correlated with reciprocal changes in the activity of AMP-activated protein kinase (AMP-PK) over the fed to starved to re-fed transition. Increases in the activity ratio of cyclic-AMP-dependent protein kinase in response to starvation lagged behind the increase in AMP-PK and the decrease in ACC activity. Changes in AMP-PK and ACC activities of rat liver closely correlated with changes in plasma insulin concentration in response to time courses of starvation and re-feeding.
Department of Pharmaceutical Chemistry, School of Pharmacy, London, U.K.
M R
MR
Munday
M R
MR
Milic
S
S
Takhar
M J
MJ
Holness
M C
MC
Sugden
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D004795:Enzyme Stability; D005260:Female; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D011092:Polyethylene Glycols; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D013217:Starvation / Q000378:metabolism*
D007328:Insulin; D009097:Multienzyme Complexes; D011092:Polyethylene Glycols; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase