Diabetes and proteolysis

Effects on carnitine palmitoyltransferase-I and malonyl-CoA binding

Khosrow Kashfi, Lauren Cagen, George Cook

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Malonyl-CoA binding and malonyl-CoA inhibition of carnitine palmitoyltransferase-1 (CPT-I) were measured in hepatic mitochondria from normal and diabetic rats and in protease-treated mitochondria from fed rats to test the hypothesis that proteolysis represents a mechanism by which diabetes produces changes in the sensitivity of CPT-I to inhibition by malonyl-CoA. As in diabetes, protease treatment increased the apparent Ki values for malonyl-CoA. Palmitoyl-CoA greatly diminished malonyl-CoA specific binding in the mitochondrial system being studied, suggesting strong competition at the malonyl-CoA binding site. Proteolysis decreased capacity for specific binding of malonyl-CoA by 60-80%, but it had no effect on binding affinity. In contrast, the decreased specific binding of malonyl-CoA seen in the diabetic state is accompanied by increased binding affinity. Furthermore, observed Kd values differed from Ki values by a factor of 10 or more, suggesting that measured Kd and Ki may represent different ligand-protein complexes. These data suggest that alterations in inhibition of CPT-I by malonyl-CoA occurring in the diabetic state may involve mechanisms other than simple proteolytic removal of malonyl-CoA binding sites.

Original languageEnglish (US)
Pages (from-to)383-388
Number of pages6
JournalLipids
Volume30
Issue number5
DOIs
StatePublished - May 1 1995

Fingerprint

Proteolysis
Malonyl Coenzyme A
Carnitine O-Palmitoyltransferase
Medical problems
Mitochondria
Rats
Peptide Hydrolases
Binding Sites
Palmitoyl Coenzyme A

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

Diabetes and proteolysis : Effects on carnitine palmitoyltransferase-I and malonyl-CoA binding. / Kashfi, Khosrow; Cagen, Lauren; Cook, George.

In: Lipids, Vol. 30, No. 5, 01.05.1995, p. 383-388.

Research output: Contribution to journalArticle

Kashfi, Khosrow ; Cagen, Lauren ; Cook, George. / Diabetes and proteolysis : Effects on carnitine palmitoyltransferase-I and malonyl-CoA binding. In: Lipids. 1995 ; Vol. 30, No. 5. pp. 383-388.
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