Citrate and the Conversion of Carbohydrate into Fat: FATTY ACID SYNTHESIS BY A COMBINATION OF CYTOPLASM AND MITOCHONDRIA

John A. Watson; John M. Lowenstein

doi:10.1016/S0021-9258(18)62653-5

CONTROL MECHANISMS AND BIOCHEMICAL GENETICS| Volume 245, ISSUE 22, P5993-6002, November 25, 1970

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Citrate and the Conversion of Carbohydrate into Fat

FATTY ACID SYNTHESIS BY A COMBINATION OF CYTOPLASM AND MITOCHONDRIA

John A. Watson
John A. Watson
Affiliations
From the Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02154
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John M. Lowenstein
John M. Lowenstein
Affiliations
From the Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02154
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Open AccessPublished:November 25, 1970DOI:https://doi.org/10.1016/S0021-9258(18)62653-5

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A cell-free system, consisting of particle-free cytoplasm and mitochondria prepared from rat liver, has been used to study the transfer of acetyl groups from the intramitochondrial to the extramitochondrial space during fatty acid synthesis. ¹⁴C-Pyruvate, generated from ¹⁴C-alanine, was used to generate intramitochondrial ¹⁴C-acetyl-CoA. Fatty acid synthesis was followed by measuring the incorporation of ³H₂O and ¹⁴C. Pool dilution experiments showed that the acetyl group of intramitochondrial acetyl-CoA leaves the mitochondria in the form of citrate, or of a closely related tricarboxylate. (-)-Hydroxycitrate, an inhibitor of citrate cleavage enzyme, strongly inhibits fatty acid synthesis from ¹⁴C-alanine. On the other hand, (-)-hydroxycitrate has little or no effect on respiration, phosphorylation, and citrate accumulation during the course of the experiments. n-Butylmalonate, an inhibitor of malate permease, also inhibits fatty acid synthesis. This inhibition is reversed by malate. n-Butylmalonate probably exerts its effect by preventing the activation of α-ketoglutarate and tricarboxylate permeases by malate. It is concluded that citrate is the major carrier in the transfer of acetyl groups from the mitochondrial matrix to the cytoplasm.

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Published online: November 25, 1970

Received: May 25, 1970

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DOI: https://doi.org/10.1016/S0021-9258(18)62653-5

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