Disease relevance of NSC628323

• Mechanism of arrhythmias induced by palmitylcarnitine in guinea pig papillary muscle [1].
• Interaction of palmitoylcarnitine with protein kinase C in neuroblastoma NB-2a cells [2].
• The amphiphilic character of palmitoylcarnitine may also explain its proposed involvement in the pathogenesis of myocardial ischemia [3].
• Perfusion of the cells with LPC or palmitoylcarnitine (2-10 microM) induced sustained tachyrhythmia with episodes of spasmodic contractures and fibrillation [4].
• The structure of CPT-2 in complex with the generic CPT inhibitor ST1326 ([R]-N-[tetradecylcarbamoyl]-aminocarnitine), a substrate analog mimicking palmitoylcarnitine and currently in clinical trials for diabetes mellitus treatment, was solved at 2.5 A resolution [5].

High impact information on NSC628323

• Our results suggest that PanK2 is located in the mitochondria to sense the levels of palmitoylcarnitine and up-regulate CoA biosynthesis in response to an increased mitochondrial demand for the cofactor to support beta-oxidation [6].
• Substrate proteins for calmodulin-sensitive and phospholipid-sensitive Ca2+-dependent protein kinases in heart, and inhibition of their phosphorylation by palmitoylcarnitine [7].
• Steady state inactivation of the maximum rate of rise of calcium-dependent action potentials was consistently shifted to more positive potentials by palmitylcarnitine (3 mV) and by elevated external calcium ion (6 mV) when the initial external calcium ion was 0.9 mM [8].
• Elevated external calcium ion, unlike palmitylcarnitine, reduced the duration of action potentials initiated from a resting potential of -80 mV [8].
• In heart mitochondria glycerophosphate has less effect on palmitylcarnitine formation because of glycerophosphate acyltransferase activity is lower and the carnitine palmityltransferase activity is higher in liver mitochondria [9].

Chemical compound and disease context of NSC628323

• Protective effects of free polyunsaturated fatty acids on arrhythmias induced by lysophosphatidylcholine or palmitoylcarnitine in neonatal rat cardiac myocytes [4].
• After the period of seven days in severe hypoxia, the palmitate, octanoate and palmitoylcarnitine oxidation rates of mitochondrial suspensions were significantly reduced when the citric acid cycle was operative [10].
• In comparison to the controls, diabetes mellitus patients excrete more long-chain carnitine esters ranging from dodecanoyl to palmitoylcarnitine [11].

Biological context of NSC628323

• Phosphorylation of endogenous substrates for the two enzyme systems was effectively inhibited by palmitoylcarnitine [7].
• Here we show that flavone-induced apoptosis is increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and the subsequent metabolic generation of O(2) (-.) in mitochondria is the initiating factor for the execution of apoptosis [12].
• Peak 14CO2 exhalation revealed a linear correlation with oxidative metabolism of palmitoylcarnitine in isolated mitochondria [13].
• Palmitylcarnitine (300 mumol.litre-1) shortened action potential duration to the same degree during metabolic block of either oxidative phosphorylation or glycolysis as it did in muscles exposed to oxygenated Krebs solution [1].
• It does not inhibit state 3 oxygen consumption in isolated hepatic mitochondria using palmitoyl-CoA or palmitoylcarnitine as substrates [14].

Anatomical context of NSC628323

• Carnitine esters of C22 fatty acids, especially erucic acid (22:1omega9,cis) are more slowly oxidized compared to palmitylcarnitine in heart than in liver mitochondria [9].
• Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate [15].
• Pretreatment of the sarcolemma with palmitoyl-CoA, palmitoylcarnitine, or lysophosphatidylcholine accelerated the initial rates (20 min) of peroxidation in a concentration-dependent manner (10-100 microM) and achieved maximal stimulation (240%, 160%, and 210%, respectively, of controls) at 50 microM concentrations of each of these amphiphiles [16].
• In vitro effects of palmitylcarnitine on cardiac plasma membrane Na,K-ATPase, and sarcoplasmic reticulum Ca2+-ATPase and Ca2+ transport [17].
• Inhibitors of protein kinase C, such as palmitoylcarnitine and sphingosine, antagonized PDBu-induced sensitization of HeLa cells to CP [18].

Associations of NSC628323 with other chemical compounds

• The Polytron mitochondria were more sensitive to ischemic arrest than were the Nagarse mitochondria with either glutamate-malate (57% vs. 22% inhibition), succinate (+ rotenone) (41% vs. 14% inhibition), or palmitoylcarnitine (57% vs. 27% inhibition) as respiratory substrates [19].
• Studies on inactivation of pyruvate dehydrogenase by palmitoylcarnitine oxidation in isolated rat heart mitochondria [20].
• Incorporation of the channel-forming antibiotic gramicidin into the membrane of human erythrocytes highly (up to 30-fold) enhances rates of reorientation (flip) of lysophosphatidylcholine and palmitoylcarnitine to the inner membrane layer after their primary incorporation into the outer layer [21].
• Rates of oxidation of palmitoyl-CoA (in the presence of L-carnitine) or of palmitoylcarnitine by non-synaptic mitochondria were extremely low, indicating that neither CPT1 nor CPT2 was likely to be rate-limiting for beta-oxidation in brain [22].
• Aminocarnitine inhibited palmitoylcarnitine formation by both of the mitochondrial CPTs and by the CPT of gradient-purified peroxisomes, but the purified peroxisomal soluble CPT was not inhibited [23].

Gene context of NSC628323

• In this single-tube reaction system palmitoylcarnitine is converted by CPT-II to free carnitine, which is subsequently esterified to acetylcarnitine by carnitine acetyltransferase [24].
• Growth cone protein-GAP-43, a PKC substrate, was co-immunoprecipitated with all the conventional and novel PKCs: palmitoylcarnitine, however, decreased its amount exclusively in the complex with PKCdelta [25].
• The protein, designated as CACL (CACT-like), is localized to the mitochondria and has palmitoylcarnitine transporting activity [26].
• Palmitoylcarnitine modulates interaction protein kinase C delta-GAP-43 [25].
• Palmitoylcarnitine, reported previously to promote neuronal differentiation, was observed to affect distribution of protein kinase C (PKC) isoforms in neuroblastoma NB-2a cells, leading to retardation in cytoplasm of high molecular weight species of PKCbeta and delta [25].

Analytical, diagnostic and therapeutic context of NSC628323

• To investigate the mechanism of arrhythmia induced by these compounds the electrophysiological effects of palmitylcarnitine (30, 100 and 300 mumol.litre-1) on guinea pig papillary muscles was examined using the microelectrode technique [1].
• The effects of l-palmitoylcarnitine or ouabain on the Na/K pump current were studied with the voltage-clamp technique in isolated guinea-pig ventricular myocytes [27].
• Determinations of intramitochondrial ratios of [acetyl-CoA]/[CoASH] by high performance liquid chromatography yielded values close to 10 for palmitoylcarnitine-supported respiration at state 4 and 2.5 at state 3 respiration [28].
• Activities for the oxidation of palmitoylcarnitine, of palmitoyl-CoA and of carnitine palmitoyltransferase were measured in mitochondria prepared from needle biopsy samples of human skeletal muscle [29].
• Conversely, with palmitoylcarnitine, post-ischemic reperfusion induced a decrease in both state III respiration rate and energy production which were more important in the EE mitochondria of the SSO group [30].

References