Temperature effects on malonyl-CoA inhibition of carnitine palmitoyltransferase I

Khosrow Kashfi, George Cook

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Malonyl-CoA inhibition of hepatic mitochondrial carnitine palmitoyltransferase I and malonyl-CoA binding were measured at temperatures ranging from O° C to 37°C. Protease treatment of mitochondria resulted in greatly diminished malonyl-CoA binding, indicating that the method used detected malonyl-CoA binding sites located on the outer surface of the mitochondrial outer membrane as expected. The apparent Ki for malonyl-CoA inhibition was found to increase with increasing temperature. Arrhenius plots for the initial velocity of the enzymatic reaction and for the Ki for malonyl-CoA both indicated a transition temperature between 20 and 25°C with the transition for the malonyl-CoA interaction being more pronounced. Total specific binding of malonyl-CoA to mitochondrial proteins increased with increasing temperature, and Kd values decreased. The opposite effect of temperature on Kd values and Ki values was surprising because it was expected that these equilibrium constants would be identical. These observations indicate that Kd values for malonyl-CoA binding and Ki values for inhibition of camitine palmitoyltransferase I by malonyl-CoA represent two significantly different binding phenomena. These data suggest that either: (a) malonyl-CoA binding measurements are unrelated to malonyl-CoA inhibition, or (b) inhibition of carnitine palmitoyltransferase I by malonyl-CoA involves more complex relationships than binding of malonyl-CoA to a single protein.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1257
Issue number2
DOIs
StatePublished - Jul 13 1995

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Malonyl Coenzyme A
Carnitine O-Palmitoyltransferase
Thermal effects
Temperature
Arrhenius plots
Mitochondria
Transition Temperature
Mitochondrial Proteins
Equilibrium constants
Mitochondrial Membranes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Endocrinology

Cite this

Temperature effects on malonyl-CoA inhibition of carnitine palmitoyltransferase I. / Kashfi, Khosrow; Cook, George.

In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, Vol. 1257, No. 2, 13.07.1995, p. 133-139.

Research output: Contribution to journalArticle

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