EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

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.

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FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

Canadian Journal of Biochemistry and Physiology ◽

10.1139/y56-091 ◽

1956 ◽

Vol 34 (1) ◽

pp. 861-868 ◽

Cited By ~ 2

Author(s):

J. D. Wood ◽

B. B. Migicovsky

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Chain Length ◽

Rat Liver ◽

Cholesterol Synthesis ◽

Rapid Decrease ◽

Acid Inhibition ◽

Degree Of Unsaturation ◽

Liver Homogenates ◽

Fatty Acid Inhibition

Fatty acids inhibit cholesterol synthesis by rat liver homogenates. Inhibition occurs with acids containing either an even or an odd number of carbon atoms in the chain, and with saturated and unsaturated acids, the inhibition increasing with the degree of unsaturation of the acid. In the case of acids with an even number of carbon atoms the inhibition increases with chain length to a maximum at 12 carbons after which a rapid decrease occurs. The presence of fatty acid during cholesterol synthesis increases the acetate incorporated into fatty acids to a slight extent. This increase is small compared with the decrease in the amount incorporated into cholesterol. A possible mechanism for the inhibition is discussed.

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FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

Canadian Journal of Biochemistry and Physiology ◽

10.1139/o56-091 ◽

1956 ◽

Vol 34 (5) ◽

pp. 861-868 ◽

Cited By ~ 10

Author(s):

J. D. Wood ◽

B. B. Migicovsky

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Chain Length ◽

Rat Liver ◽

Cholesterol Synthesis ◽

Rapid Decrease ◽

Acid Inhibition ◽

Degree Of Unsaturation ◽

Liver Homogenates ◽

Fatty Acid Inhibition

Fatty acids inhibit cholesterol synthesis by rat liver homogenates. Inhibition occurs with acids containing either an even or an odd number of carbon atoms in the chain, and with saturated and unsaturated acids, the inhibition increasing with the degree of unsaturation of the acid. In the case of acids with an even number of carbon atoms the inhibition increases with chain length to a maximum at 12 carbons after which a rapid decrease occurs. The presence of fatty acid during cholesterol synthesis increases the acetate incorporated into fatty acids to a slight extent. This increase is small compared with the decrease in the amount incorporated into cholesterol. A possible mechanism for the inhibition is discussed.

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Conversion of [U−14C]glucose into carbon dioxide, glycogen, cholesterol and fatty acids in liver slices from embryonic and growing chicks

Biochemical Journal ◽

10.1042/bj1080655 ◽

1968 ◽

Vol 108 (4) ◽

pp. 655-661 ◽

Cited By ~ 78

Author(s):

Alan G. Goodridge

Keyword(s):

Carbon Dioxide ◽

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Synthesis ◽

Glucose Oxidation ◽

Glycogen Synthesis ◽

Liver Glycogen ◽

Acid Synthesis ◽

Low Fat Diet ◽

Liver Slices

Incorporation of [U−14C]glucose into carbon dioxide, glycogen, cholesterol and fatty acids and of 3H2O into cholesterol and fatty acids was measured in liver slices from embryos and growing chicks. During the embryonic period, rates of incorporation were low and stable for all pathways. Fatty acid synthesis and glucose oxidation increased promptly when the chicks were fed, reaching plateau levels within 6 days. Cholesterol and glycogen synthesis increased only slightly when the birds were fed. After 5 and 11 days respectively, cholesterol and glycogen synthesis began to increase rapidly. The rate of glucose oxidation in liver slices from 4-week-old chicks was 20-fold greater than in slices of embryonic liver; glycogen, cholesterol and fatty acid synthesis had increased approximately 100-, 300- and 1000-fold respectively. The increase in the metabolism of [U−14C]glucose that occurred after hatching was probably due to the change from a high-fat non-carbohydrate diet (yolk) to a high-carbohydrate low-fat diet (mash).

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

Biochemical Journal ◽

10.1042/bj1470531 ◽

1975 ◽

Vol 147 (3) ◽

pp. 531-539 ◽

Cited By ~ 7

Author(s):

D P Bloxham

Keyword(s):

Fatty Acid ◽

Rat Liver ◽

Fatty Acid Synthesis ◽

Cholesterol Synthesis ◽

Alkylating Agents ◽

Selective Inhibition ◽

Acid Synthesis ◽

Fatty Acyl ◽

Sterol Synthesis ◽

Effective Inhibitor

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.

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