Stereoisomeric acylamidomorpholinium carnitine analogues: Selective inhibitors of carnitine palmitoyltransferase I and II
5
Citation
23
Reference
10
Related Paper
Citation Trend
Keywords:
Carnitine O-palmitoyltransferase
Carnitine palmitoyltransferase I
Microsoma
Transferase
The functional molecular sizes of the protein(s) mediating the carnitine palmitoyltransferase I (CPT I) activity and the [14C]malonyl-CoA binding in purified outer-membrane preparations from rat liver mitochondria were determined by radiation-inactivation analysis. In all preparations tested the dose-dependent decay in [14C]malonyl-CoA binding was less steep than that for CPT I activity, suggesting that the protein involved in malonyl-CoA binding may be smaller than that catalysing the CPT I activity. The respective sizes computed from simultaneous analysis for molecular-size standards exposed under identical conditions were 60,000 and 83,000 DA for malonyl-CoA binding and CPT I activity respectively. In irradiated membranes the sensitivity of CPT activity to malonyl-CoA inhibition was increased, as judged by malonyl-CoA inhibition curves for the activity in control and in irradiated membranes that had received 20 Mrad radiation and in which CPT activity had decayed by 60%. Possible correlations between these data and other recent observations on the CPT system are discussed.
Carnitine palmitoyltransferase I
Carnitine O-palmitoyltransferase
Malonyl-CoA
Cite
Citations (47)
A soluble extract was obtained on treatment of rat liver mitochondrial outer membranes with cholate which bound ( 14 C]malonyl‐CoA but was essentially free of carnitine palmitoyltransferase (CPT) activity. Extraction of mitochondrial inner membranes with cholate readily solubilized a CPT activity which was insensitive to malonyl‐CoA. Combination of these two extracts caused the CPT derived from inner membranes to become inhibitable by malonyl‐CoA.
Malonyl-CoA
Carnitine palmitoyltransferase I
Carnitine O-palmitoyltransferase
Inner membrane
Cite
Citations (27)
Carnitine palmitoyltransferase I
Carnitine O-palmitoyltransferase
Cite
Citations (17)
Carnitine O-palmitoyltransferase
Carnitine palmitoyltransferase I
Cite
Citations (63)
The kinetics of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) were examined in mitochondria from rat liver, heart and skeletal muscle as a function of pH over the range 6.8-7.6. In all three tissues raising the pH resulted in a fall in the Km for carnitine, no change in the Km for palmitoyl-CoA or Octanoyl-CoA, and a marked decrease in the inhibitory potency of malonyl-CoA. Studies with skeletal-muscle mitochondria established that increasing pH was accompanied by an increase in the Kd of the malonyl-CoA binding site for this ligand, coupled with a decrease in the Kd for fatty acyl-CoA species to compete for malonyl-CoA binding. Three principal conclusions are drawn. (1) The pH-induced shift in malonyl-CoA sensitivity of CPT I is not a phenomenon restricted to liver mitochondria. (2) At any given pH within the range tested, the ability of malonyl-CoA (and closely related compounds) to inhibit enzyme activity is governed by the efficiency of their binding to the malonyl-CoA site. (3) The competitive interaction between fatty acyl-CoA substrates and malonyl-CoA as regards CPT I activity is exerted at the malonyl-CoA binding site. Finally, the possibility is strengthened that the malonyl-CoA binding site is distinct from the active site of CPT I.
Malonyl-CoA
Carnitine O-palmitoyltransferase
Carnitine palmitoyltransferase I
Acyl-CoA
Cite
Citations (78)
Malonyl-CoA
Transferase
Carnitine O-palmitoyltransferase
Carnitine palmitoyltransferase I
Cite
Citations (251)
Malonyl-CoA
Carnitine O-palmitoyltransferase
Carnitine palmitoyltransferase I
Acetyl-CoA Carboxylase
Cite
Citations (9)
A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.
Clofibric acid
Clofibrate
Carnitine palmitoyltransferase I
Carnitine O-palmitoyltransferase
Cite
Citations (37)
Carnitine palmitoyltransferase I
Carnitine O-palmitoyltransferase
Malonyl-CoA
Acyltransferases
Acyltransferases
Protein family
Cite
Citations (256)