| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 269, Issue 42, 26443-26448, 10, 1994
BC Weis, AT Cowan, N Brown, DW Foster and JD McGarry
It has recently been established that rat heart mitochondria contain two
isoforms of carnitine palmitoyltransferase I (CPT I), the minor 88- kDa
variant being identical to liver CPT I (L-CPT I) and the dominant 82-kDa
form resembling the skeletal muscle enzyme (M-CPT I) (Weis, B. C., Esser,
V., Foster, D. W., and McGarry, J. D. (1994) J. Biol. Chem. 269,
18712-18715). To quantify the functional contribution of L-CPT I to overall
CPT I activity in heart mitochondria a selective inhibitor of the former
was needed. The dinitrophenol analog of 2[6-(4-
chlorophenoxy)hexyl]oxirane-2-carboxylic acid (etomoxir) (DNP-Et) was found
to have this property. When liver and skeletal muscle mitochondria were
exposed to DNP-Et in the presence of ATP and CoASH, the DNP-Et-CoA formed
completely inhibited liver CPT I while leaving the muscle enzyme
unaffected. Similar treatment of heart mitochondria blocked only the L-CPT
I component. This had the effect of shifting the apparent Km for carnitine
from approximately 200 to approximately 500 microM and the I50 value for
malonyl-CoA (the concentration needed to suppress enzyme activity by 50%)
from approximately 0.18 to approximately 0.06 microM, i.e. the heart system
now behaved exactly the same as that from skeletal muscle. Taking the Km
for carnitine of L- CPT I and M-CPT I to be 30 and 500 microM,
respectively, it could be calculated that the former contributes
approximately 2% to the total CPT I in heart. When the 82-kDa CPT I
isoforms of heart and skeletal muscle were labeled with [3H]etomoxir and
then exposed to trypsin, the fragmentation patterns obtained were identical
and quite distinct from that given by CPT I from liver. We conclude that
(i) DNP-Et, unlike other agents of the oxirane carboxylic acid class, has
remarkable inhibitory selectivity for L-CPT I over M-CPT I; (ii) the
previously puzzling observation that rat heart CPT I displays kinetic
characteristics intermediate between those of the enzymes from liver and
skeletal muscle is entirely accounted for by the low level expression of
L-CPT I in the cardiac myocyte; and (iii) the dominant 82- kDa CPT I
isoform in heart is identical to the muscle enzyme. The data reaffirm that,
in contrast to CPT II, CPT I exists in at least two isoforms and that both
are present in rat heart.
Use of a selective inhibitor of liver carnitine palmitoyltransferase I (CPT I) allows quantification of its contribution to total CPT I activity in rat heart. Evidence that the dominant cardiac CPT I isoform is identical to the skeletal muscle enzyme
Department of Internal Medicine, University of Texas Southwestern Medical Center, Southwestern Medical School, Dallas 75235.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. A. Haynes, J. C. Allegood, K. Sims, E. W. Wang, M. C. Sullards, and A. H. Merrill Jr. Quantitation of fatty acyl-coenzyme As in mammalian cells by liquid chromatography-electrospray ionization tandem mass spectrometry J. Lipid Res., May 1, 2008; 49(5): 1113 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Murthy, H. Tong, and R. J. Hohl Regulation of Fatty Acid Synthesis by Farnesyl Pyrophosphate J. Biol. Chem., December 23, 2005; 280(51): 41793 - 41804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu, G. Zheng, M. Treber, J. Dai, and G. Woldegiorgis Cysteine-scanning Mutagenesis of Muscle Carnitine Palmitoyltransferase I Reveals a Single Cysteine Residue (Cys-305) Is Important for Catalysis J. Biol. Chem., February 11, 2005; 280(6): 4524 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Bartelds, J. Takens, G. B. Smid, V. A. Zammit, C. Prip-Buus, J. R. G. Kuipers, and F. R. van der Leij Myocardial carnitine palmitoyltransferase I expression and long-chain fatty acid oxidation in fetal and newborn lambs Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2243 - H2248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Feingold, M. S. Kim, J. Shigenaga, A. Moser, and C. Grunfeld Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E201 - E207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Napal, J. Dai, M. Treber, D. Haro, P. F. Marrero, and G. Woldegiorgis A Single Amino Acid Change (Substitution of the Conserved Glu-590 with Alanine) in the C-terminal Domain of Rat Liver Carnitine Palmitoyltransferase I Increases its Malonyl-CoA Sensitivity Close to That Observed with the Muscle Isoform of the Enzyme J. Biol. Chem., September 5, 2003; 278(36): 34084 - 34089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hardy, W. El-Assaad, E. Przybytkowski, E. Joly, M. Prentki, and Y. Langelier Saturated Fatty Acid-induced Apoptosis in MDA-MB-231 Breast Cancer Cells: A ROLE FOR CARDIOLIPIN J. Biol. Chem., August 22, 2003; 278(34): 31861 - 31870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Treber, J. Dai, and G. Woldegiorgis Identification by Mutagenesis of Conserved Arginine and Glutamate Residues in the C-terminal Domain of Rat Liver Carnitine Palmitoyltransferase I That Are Important for Catalytic Activity and Malonyl-CoA Sensitivity J. Biol. Chem., March 21, 2003; 278(13): 11145 - 11149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Besikci, F. M. Campbell, T. A. Hopkins, J. R. B. Dyck, and G. D. Lopaschuk Relative importance of malonyl CoA and carnitine in maturation of fatty acid oxidation in newborn rabbit heart Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H283 - H289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zheng, J. Dai, and G. Woldegiorgis Identification by Mutagenesis of a Conserved Glutamate (Glu487) Residue Important for Catalytic Activity in Rat Liver Carnitine Palmitoyltransferase II J. Biol. Chem., October 25, 2002; 277(44): 42219 - 42223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fingerhut, W. Roschinger, A. C. Muntau, T. Dame, J. Kreischer, R. Arnecke, A. Superti-Furga, H. Troxler, B. Liebl, B. Olgemoller, et al. Hepatic Carnitine Palmitoyltransferase I Deficiency: Acylcarnitine Profiles in Blood Spots Are Highly Specific Clin. Chem., October 1, 2001; 47(10): 1763 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. DeGrado, S. Wang, and D. C. Rockey Preliminary Evaluation of 15-[18F]Fluoro-3-oxa-pentadecanoate as a PET Tracer of Hepatic Fatty Acid Oxidation J. Nucl. Med., October 1, 2000; 41(10): 1727 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Woldegiorgis, J. Shi, H. Zhu, and D. N. Arvidson Functional Characterization of Mammalian Mitochondrial Carnitine Palmitoyltransferases I and II Expressed in the Yeast Pichia pastoris J. Nutr., February 1, 2000; 130(2): 310 - 310. [Abstract] [Full Text]
|
|
|
|
|
|
J. Shi, H. Zhu, D. N. Arvidson, and G. Woldegiorgis A Single Amino Acid Change (Substitution of Glutamate 3 with Alanine) in the N-terminal Region of Rat Liver Carnitine Palmitoyltransferase I Abolishes Malonyl-CoA Inhibition and High Affinity Binding J. Biol. Chem., April 2, 1999; 274(14): 9421 - 9426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Adams, V. Esser, N. F. Brown, N. H. Ing, L. Johnson, D. W. Foster, and J. D. McGarry Expression and Possible Role of Muscle-Type Carnitine Palmitoyltransferase I during Sperm Development in the Rat Biol Reprod, December 1, 1998; 59(6): 1399 - 1405. [Abstract] [Full Text]
|
|
|
|
|
|
I. Schmidt and P. Herpin Carnitine Palmitoyltransferase I (CPT I) Activity and Its Regulation by Malonyl-CoA Are Modulated by Age and Cold Exposure in Skeletal Muscle Mitochondria from Newborn Pigs J. Nutr., May 1, 1998; 128(5): 886 - 893. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. W. Brownsey, A. N. Boone, and M. F. Allard Actions of insulin on the mammalian heart: metabolism, pathology and biochemical mechanisms Cardiovasc Res, April 1, 1997; 34(1): 3 - 24. [Full Text] [PDF]
|
|
|
|
|
|
Y. Xia, L. M. Buja, and J. B. McMillin Change in Expression of Heart Carnitine Palmitoyltransferase I Isoforms with Electrical Stimulation of Cultured Rat Neonatal Cardiac Myocytes J. Biol. Chem., May 17, 1996; 271(20): 12082 - 12087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Esser, N. F. Brown, A. T. Cowan, D. W. Foster, and J. D. McGarry Expression of a cDNA Isolated from Rat Brown Adipose Tissue and Heart Identifies the Product as the Muscle Isoform of Carnitine Palmitoyltransferase I (M-CPT I) J. Biol. Chem., March 22, 1996; 271(12): 6972 - 6977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kudo, A. J. Barr, R. L. Barr, S. Desai, and G. D. Lopaschuk High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5`-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase J. Biol. Chem., July 21, 1995; 270(29): 17513 - 17520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Brown, B. C. Weis, J. E. Husti, D. W. Foster, and J. D. McGarry Mitochondrial Carnitine Palmitoyltransferase I Isoform Switching in the Developing Rat Heart J. Biol. Chem., April 14, 1995; 270(15): 8952 - 8957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dai, H. Zhu, J. Shi, and G. Woldegiorgis Identification by Mutagenesis of Conserved Arginine and Tryptophan Residues in Rat Liver Carnitine Palmitoyltransferase I Important for Catalytic Activity J. Biol. Chem., July 14, 2000; 275(29): 22020 - 22024. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
