Myocardial carnitine palmitoyltransferase of the mitochondrial outer membrane is not altered by fasting

Randall L. Mynatt, Michael D. Lappi, George Cook

Research output: Contribution to journalArticle

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Abstract

The regulation of heart carnitine palmitoyltransferase was studied during the transition to the fasting state. Using decanoyl-CoA or palmitoyl-CoA as substrates, we found no differences in carnitine palmitoyltransferase activity on in its sensitivity to inhibition by malonyl-CoA between fed and fasted states. No cooperativity was seen with either substrate, and the malonyl-CoA-induced shift to sigmoid kinetics normally observed with liver mitochondria was not obvious with heart mitochondria. Analysis of malonyl-CoA inhibition data revealed that mitochondria from rat heart exhibited incomplete maximum inhibition of carnitine palmitoyltransferase (partial inhibition). Homogenization of intact liver mitochondria resulted in a similar pattern of incomplete inhibition and suggested that the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner membrane was also being assayed. Carnitine palmitoyltransferase in mitochondrial outer membranes, isolated from the heart, proved to be extremely sensitive to malonyl-CoA inhibition and had maximum inhibition values of 90-100% with either decanoyl-CoA or palmitoyl-CoA as substrates, but fasting had no effect. Fasting produced no change in the Ki for malonyl-CoA (0.10 ± 0.04 and 0.14 ± 0.02 μM for the fed and fasted groups, respectively). Acyl-CoA chain length specificity was C10 > C16 > C14 > C12 > C18 = C8 for carnitine palmitoyltransferase in heart mitochondrial outer membranes. It is concluded that the regulation of carnitine palmitoyltransferase of heart mitochondrial outer membranes differs from regulation of the liver enzyme in three characteristics - the heart enzyme (a) has greater sensitivity to malonyl-CoA inhibition, (b) is resistant to the effects of fasting and (c) has somewhat different acyl-CoA substrate specificity.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1128
Issue number1
DOIs
StatePublished - Sep 22 1992

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Malonyl Coenzyme A
Carnitine O-Palmitoyltransferase
Mitochondrial Membranes
Fasting
Mitochondria
Membranes
Liver
Palmitoyl Coenzyme A
Acyl Coenzyme A
Heart Mitochondria
Substrates
Liver Mitochondrion
Enzymes
Inhibition (Psychology)
Chain length
Sigmoid Colon
Substrate Specificity
Rats
Kinetics

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Endocrinology

Cite this

Myocardial carnitine palmitoyltransferase of the mitochondrial outer membrane is not altered by fasting. / Mynatt, Randall L.; Lappi, Michael D.; Cook, George.

In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, Vol. 1128, No. 1, 22.09.1992, p. 105-111.

Research output: Contribution to journalArticle

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abstract = "The regulation of heart carnitine palmitoyltransferase was studied during the transition to the fasting state. Using decanoyl-CoA or palmitoyl-CoA as substrates, we found no differences in carnitine palmitoyltransferase activity on in its sensitivity to inhibition by malonyl-CoA between fed and fasted states. No cooperativity was seen with either substrate, and the malonyl-CoA-induced shift to sigmoid kinetics normally observed with liver mitochondria was not obvious with heart mitochondria. Analysis of malonyl-CoA inhibition data revealed that mitochondria from rat heart exhibited incomplete maximum inhibition of carnitine palmitoyltransferase (partial inhibition). Homogenization of intact liver mitochondria resulted in a similar pattern of incomplete inhibition and suggested that the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner membrane was also being assayed. Carnitine palmitoyltransferase in mitochondrial outer membranes, isolated from the heart, proved to be extremely sensitive to malonyl-CoA inhibition and had maximum inhibition values of 90-100{\%} with either decanoyl-CoA or palmitoyl-CoA as substrates, but fasting had no effect. Fasting produced no change in the Ki for malonyl-CoA (0.10 ± 0.04 and 0.14 ± 0.02 μM for the fed and fasted groups, respectively). Acyl-CoA chain length specificity was C10 > C16 > C14 > C12 > C18 = C8 for carnitine palmitoyltransferase in heart mitochondrial outer membranes. It is concluded that the regulation of carnitine palmitoyltransferase of heart mitochondrial outer membranes differs from regulation of the liver enzyme in three characteristics - the heart enzyme (a) has greater sensitivity to malonyl-CoA inhibition, (b) is resistant to the effects of fasting and (c) has somewhat different acyl-CoA substrate specificity.",
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