No abstract

Arrhenius plots were generated on the activity of rat liver mitochondrial cytochrome c oxidase from Metrecal-sucrose fed controls and Metrecal-alcohol fed experimentals. Chronic alcohol feeding resulted in diminished specific activity of cytochrome c oxidase and abolition of the discontinuity temperature at 17.5 degrees C found in the controls. Twenty-four hours after alcohol withdrawal, a discontinuity temperature reappeared at 14.4 degrees C; at 48 h it increased to 22.6 degrees C and returned to normal (17.4 degrees C) at 72 h. Such liver mitochondria also showed a decreased capacity to oxidize the acetyl group of acetyl carnitine immediately following prolonged alcohol feeding. When the assay was performed following withdrawal from alcohol 24 h later, oxidation was enhanced and this effect persisted for another 48 h. These latter results revealed a diminished capacity of such mitochondria to oxidize short chain fatty acids during alcohol feeding and the reverse during alcohol withdrawal. These results, complemented by thermographic data obtained through differential scanning calorimetry (DSC) reinforced the view that chronic alcoholic feeding induced adaptive changes in the fluidity of rat liver mitochondrial membrane lipids. Moreover, they demonstrated that in the microenvironment of the membrane-bound enzymes on withdrawal from ethanol, the membrane readapts to the new conditions without alcohol. This involved modulation of membrane structure and function and at the same time demonstrated a role for the membrane in the expression of tolerance and functional dependence on alcohol.

No abstract

Acetyl-l-carnitylcholine (l-ACCh) was identified in rat brain extracts on paper chromatograms developed in butanol–water for 138 h. l-ACCh was also identified in brain extracts fractionated on t.l.c. plates and on Sephadex G-10 columns. In every instance l-ACCh was separated from the acetylcholine (ACh) present and the ACh-like activity of l-ACCh was about 20% of the total activity in the extract. Both l-ACCh and ACh were found to be inseparable in a variety of chromatographic systems including electrophoresis. Treatment of these choline esters with cholinesterases showed that while true acetylcholinesterase hydrolyzed both l-ACCh and ACh, pseudocholinesterase destroyed only ACh. On a molar basis, the ACh-like activity of ACCh is one-half that of ACh on both the guinea pig ileum and frog rectus preparations. Like ACh, the ratio of the nicotinic to muscarinic potency of l-ACCh is unity. Mixtures of l-ACCh and ACh show summation of ACh-like activity on both the guinea pig ileum and frog rectus preparations.

Rat hepatic plasma membranes isolated after chronic alcohol feeding displayed a different buoyant density range with a significantly increased peak density value when spun isopycnically in a 30-50% sucrose (w/w) gradient. This change persisted up to 48 h of withdrawal from alcohol. Analysis of membrane lipids revealed certain significant alterations in the phospholipids as well as the fatty acyl composition in individual phospholipids of the experimental plasma membranes. During withdrawal of alcohol for 48 h, all the alcohol-induced changes in the phospholipids returned to normal. Most initial changes in fatty acids reverted to the control composition during this time, but new changes in fatty acyl distribution were also observed. These were interpreted to represent readaptation to the withdrawal of the alcohol. It is not established how long this readaptation period lasts.