scholarly journals Selective inhibition of cholesterol synthesis by cell-free preparations of rat liver by using inhibitors of cytoplasmic acetoacetyl-coenzyme A thiolase.

1975 ◽  
Vol 147 (3) ◽  
pp. 531-539 ◽  
Author(s):  
D P Bloxham

Cytoplasmic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 2.3.1.9) was partially purified from rat liver. The enzyme was irreversibly inactivated by 4-bromocrotonyl-CoA, but-3-ynoyl-CoA, pent-3-ynoyl-CoA and dec-3-ynoyl-CoA. In the case of the alk-3-ynoyl-CoA esters the potency as alkylating agents of acetoacetyl-CoA thiolase decreased with increased chain length of the alk-3-ynoyl moiety. Advantage was taken of the specific action of alk-3-ynoyl-CoA esters on acetoacetyl-CoA thiolase to show that in a postmitochondrial fraction from rat liver they are effective inhibitors of cholesterol synthesis from sodium [2-14C]acetate under conditions when mevalonate conversion into cholesterol and fatty acid synthesis are unafffected. Short-chain alk-3-ynoic acids have little effect on sterol synthesis, although dec-3-ynoic acid is an effective inhibitor owing to its conversion into the CoA ester by the microsomal fatty acyl-CoA synthetase.

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.


1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.


1995 ◽  
Vol 74 (2) ◽  
pp. 209-219 ◽  
Author(s):  
Christian Demigné ◽  
Christine Morand ◽  
Marie-Anne Levrat ◽  
Catherine Besson ◽  
Corinne Moundras ◽  
...  

In the present study the actual role of propionic acid in the control of fatty acid and cholesterol synthesis was investigated in isolated liver cells from fed rats maintained in the presence of near-physiological concentrations of glucose, glutamine and acetate. Using 3H2O for lipid labelling, propionate appears as an effective inhibitor of fatty acid synthesis and to a lesser extent of cholesterol synthesis, even at the lowest concentration used (0·6 mmol/l). Butyrate is a potent activator of both synthetic pathways, and the activating effect was not counteracted by propionate. Using 1-[14C]acetate, it was observed that propionate at a moderate concentration, or 1 mmol oleate/l, are both very effective inhibitors of 14C incorporation into fatty acid and cholesterol. This incorporation was drastically inhibited when propionate and oleate were present together in the incubation medium. The net utilization of acetate by rat hepatocytes was impaired by propionate, in contrast to oleate. 1-[14C]butyrate was utilized at a high rate for fatty acid synthesis, but to a lesser extent for cholesterol synthesis; both processes were unaffected by propionate. Intracellular citrate concentration was not markedly depressed by propionate, whereas it was strongly elevated by butyrate. In conclusion, propionate may represent an effective inhibitor of lipid synthesis when acetate is a major source of acetyl-CoA, a situation which is encountered with diets rich in readily-fermentable fibres. The present findings also suggest that propionate may be effective at concentrations close to values measured in vivo in the portal vein.


1953 ◽  
Vol 205 (1) ◽  
pp. 401-408
Author(s):  
Grace Medes ◽  
Morris A. Spirtes ◽  
Sidney Weinhouse

1973 ◽  
Vol 248 (2) ◽  
pp. 738-739
Author(s):  
Christian A. Barth ◽  
H. Jürgen Hackenschmidt ◽  
Elmar E. Weis ◽  
Karl F.A. Decker

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