Independence of cholesterol and fatty acid biosynthesis from cyclic adenosine monophosphate concentration in the perfused rat liver

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Abstract

Cyclic adenosine 3':5' monophosphate (cyclic AMP), when added in a concentration of 5 mM to incubations of rat liver slices with [1 14C]acetate or [1 14C] octanoate, markedly depress both cholesterol and fatty acid biosynthesis but not CO2 or ketone body production. The inhibitory effects of the nucleotide were lost when its concentration was reduced to 0.5 mM. These findings confirm and extend those made by others. However, it was also observed that perfusion of rat livers with the above mentioned substrates in the presence of sufficient glucagon to raise the tissue cyclic AMP level by at least 50 fold was totally without effect on rates of cholesterol or fatty acid synthesis. In addition, such treatment of the livers failed to reduce the activity of 3 hydroxy 3 methyl glutaryl coenzyme A reductase in subsequently isolated microsomes. In the intact liver, cholesterol and fatty acid synthesis are independent of acutely induced changes in the intracellular cyclic AMP concentration over a very wide physiological range.

Original languageEnglish (US)
Pages (from-to)6029-6032
Number of pages4
JournalJournal of Biological Chemistry
Volume249
Issue number19
StatePublished - 1974

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Biosynthesis
Liver
Cyclic AMP
Rats
Fatty Acids
Cholesterol
Adenosine
Ketone Bodies
Microsomes
Glucagon
Oxidoreductases
Acetates
Nucleotides
Perfusion
Tissue
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "Cyclic adenosine 3':5' monophosphate (cyclic AMP), when added in a concentration of 5 mM to incubations of rat liver slices with [1 14C]acetate or [1 14C] octanoate, markedly depress both cholesterol and fatty acid biosynthesis but not CO2 or ketone body production. The inhibitory effects of the nucleotide were lost when its concentration was reduced to 0.5 mM. These findings confirm and extend those made by others. However, it was also observed that perfusion of rat livers with the above mentioned substrates in the presence of sufficient glucagon to raise the tissue cyclic AMP level by at least 50 fold was totally without effect on rates of cholesterol or fatty acid synthesis. In addition, such treatment of the livers failed to reduce the activity of 3 hydroxy 3 methyl glutaryl coenzyme A reductase in subsequently isolated microsomes. In the intact liver, cholesterol and fatty acid synthesis are independent of acutely induced changes in the intracellular cyclic AMP concentration over a very wide physiological range.",
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T1 - Independence of cholesterol and fatty acid biosynthesis from cyclic adenosine monophosphate concentration in the perfused rat liver

AU - Raskin, Philip

AU - McGarry, J. D.

AU - Foster, Daniel W

PY - 1974

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N2 - Cyclic adenosine 3':5' monophosphate (cyclic AMP), when added in a concentration of 5 mM to incubations of rat liver slices with [1 14C]acetate or [1 14C] octanoate, markedly depress both cholesterol and fatty acid biosynthesis but not CO2 or ketone body production. The inhibitory effects of the nucleotide were lost when its concentration was reduced to 0.5 mM. These findings confirm and extend those made by others. However, it was also observed that perfusion of rat livers with the above mentioned substrates in the presence of sufficient glucagon to raise the tissue cyclic AMP level by at least 50 fold was totally without effect on rates of cholesterol or fatty acid synthesis. In addition, such treatment of the livers failed to reduce the activity of 3 hydroxy 3 methyl glutaryl coenzyme A reductase in subsequently isolated microsomes. In the intact liver, cholesterol and fatty acid synthesis are independent of acutely induced changes in the intracellular cyclic AMP concentration over a very wide physiological range.

AB - Cyclic adenosine 3':5' monophosphate (cyclic AMP), when added in a concentration of 5 mM to incubations of rat liver slices with [1 14C]acetate or [1 14C] octanoate, markedly depress both cholesterol and fatty acid biosynthesis but not CO2 or ketone body production. The inhibitory effects of the nucleotide were lost when its concentration was reduced to 0.5 mM. These findings confirm and extend those made by others. However, it was also observed that perfusion of rat livers with the above mentioned substrates in the presence of sufficient glucagon to raise the tissue cyclic AMP level by at least 50 fold was totally without effect on rates of cholesterol or fatty acid synthesis. In addition, such treatment of the livers failed to reduce the activity of 3 hydroxy 3 methyl glutaryl coenzyme A reductase in subsequently isolated microsomes. In the intact liver, cholesterol and fatty acid synthesis are independent of acutely induced changes in the intracellular cyclic AMP concentration over a very wide physiological range.

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