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

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
Search for articles by this author
John M. Lowenstein
John M. Lowenstein
Affiliations
From the Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02154
Search for articles by this author

Open AccessPublished:November 25, 1970DOI:https://doi.org/10.1016/S0021-9258(18)62653-5

This paper is only available as a PDF. To read, Please Download here.

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.

REFERENCES

- Watson J.A.
- Lowenstein J.M.
Fed. Proc. 1970; 29: 676
- Google Scholar
- Lowenstein J.M.
Biochem. Soc. Symp. 1968; 27: 61
- Google Scholar
- Watson J.A.
- Fang M.
- Lowenstein J.M.
Arch. Biochem. Biophys. 1969; 135: 209
- Google Scholar
- Kornackek M.S.
- Lowenstein J.M.
Biochem. J. 1965; 94: 209
- Google Scholar
- Myers D.K.
- Slater E.C.
Biochem. J. 1957; 67: 572
- Google Scholar
- Estabrook R.W.
Estabrook R.W. Pullman M.E. Methods in enzymology. 10. Academic Press, New York1967: 41
- Google Scholar
- Fang M.
- Lowenstein J.M.
Biochem. J. 1967; 105: 803
- Google Scholar
- Jungas R.L.
Biochemistry. 1968; 7: 3708
- Google Scholar
- D’Adamo Jr., A.F.
- Haft D.E.
Fed. Proc. 1962; 21: 6
- Google Scholar
- D’Adamo Jr., A.F.
- Haft D.E.
J. Biol. Chem. 1965; 240: 613
- Google Scholar
- Abraham S.
- Madsen J.
- Chaikoff I.L.
J. Biol. Chem. 1964; 239: 855
- Google Scholar
- Bhaduri A.
- Srerb P.A.
J. Biol. Chem. 1964; 239: 1357
- Google Scholar
- Bremer J.
J. Biol. Chem. 1962; 237: 2228
- Google Scholar
- Nobum K.R.
- Bremer J.
Biochim. Biophys. Acta. 1963; 78: 77
- Google Scholar
- Bressler R.
- Katz R.I.
J. Biol. Chem. 1965; 240: 622
- Google Scholar
- Marquis N.R.
- Fritz I.B.
J. Biol. Chem. 1965; 240: 2193
- Google Scholar
- Klingenberg M.
- Beenakers A.M.T.
Biochim. Biophys. Acta. 1963; 84: 205
- Google Scholar
- Norum K.R.
- Bremer J.
J. Biol. Chem. 1967; 242: 407
- Google Scholar
- Lowenstein J.M.
Dickens F. Neil E. Oxygen in the animal organism. Pergamon Press, New York1964: 163
- Google Scholar
- Chappell J.B.
Brit. Med. Bull. 1968; 24: 150
- Google Scholar
- Chappell J.B.
- Robinson B.H.
Biochem. Soc. Symp. 1968; 27: 123
- Google Scholar
- Tager J.M.
- de Haan E.J.
- Slater E.C.
Lowenstein J.M. Citric acid cycle. Control and compartmentation. Marcel Dekker, New York1969: 213
- Google Scholar
- Bressler R.
- Brendel K.
J. Biol. Chem. 1966; 241: 4092
- Google Scholar
- Daikuhara Y.
- Tsunemi T.
- Takeda Y.
Biochim. Biophys. Acta. 1968; 158: 51
- Google Scholar

Article info

Publication history

Published online: November 25, 1970

Received: May 25, 1970

Identification

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

Copyright

User license

Creative Commons Attribution (CC BY 4.0) |

How you can reuse Information Icon

ScienceDirect

Access this article on ScienceDirect

Toggle Thumbstrip

Property	Value
Status
Version
Ad File
Disable Ads Flag
Environment
Moat Init
Moat Ready
Contextual Ready
Contextual URL
Contextual Initial Segments
Contextual Used Segments
AdUnit
SubAdUnit
Custom Targeting
Ad Events
Invalid Ad Sizes