Disease relevance of Cpt2

• The cDNA encoding rat liver carnitine palmitoyltransferase II (CPT-II) was heterologously expressed using a recombinant baculovirus/insect cell system [1].
• Unlike Escherichia coli, the baculovirus-infected insect cells expressed mostly soluble active recombinant CPT-II (rCPT-II) [1].
• This study was devised to investigate the effect of CARN on altered CPT I and CPT II activity in the cardiomyopathy associated with ADR therapy [2].
• This study supports the concept that ADR toxicity results from the inhibition of both CPT I and CPT II activities and that one of the causes of ADR-induced cardiomyopathy is a result of globally impaired fatty acid oxidation [2].
• These changes in metabolic zonation, together with decreased CPT II activity, may contribute to the aggravation of cachexia [3].

High impact information on Cpt2

• By contrast, Glut-2, acyl-CoA synthetase, and CPT II gene expression was not affected by benfluorex or S 422-1 [4].
• However, whether their site of action is at the level of CPT I (outer membrane), CPT II (inner membrane), carnitine-acylcarnitine translocase (CACT, inner membrane), or some combination of these elements has never been resolved [5].
• Moreover, protein immunoblotting analysis showed that CPT-I, as well as the inner CPT-II, was localized in the mitoplast fraction [6].
• Positive Western blots were obtained, with the particle using anti-CPTi/CPT-II at a molecular weight identical with the CPT1/CPT-II purified from rat heart mitochondria [7].
• Expression and analysis of site-directed mutants of CPT II showed that histidine 372, as well as aspartates 376 and 464 (all conserved throughout the carnitine/choline acyltransferase family), are essential for catalytic activity [8].

Chemical compound and disease context of Cpt2

• Rats treated orally for 21 days with aminocarnitine, an inhibitor of carnitine palmitoyltransferase-2 (CPT-2), do not show hypertrophy of the heart [9].

Biological context of Cpt2

• The predicted amino acid sequence of CPT II shows strong identity with those of two other acyltransferases, namely, rat liver peroxisomal carnitine octanoyltransferase and porcine choline acetyltransferase [10].
• These data indicate that the catalytic subunit of CPTo/CPT-I is the same as CPTi/CPT-II [7].
• The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II [11].
• As CPT-1 and CPT-2 are both required for the oxidation of long-chain fatty acids in mitochondria, it can be concluded that inhibition of fatty acid oxidation per se is not responsible for cell growth, but rather the accumulation of a metabolite, probably long-chain acylcoenzyme A [9].

Anatomical context of Cpt2

• Inhibition of transferase activity by 4-THA and malonyl-CoA was attenuated in mitochondria which had been solubilized with octyl glucoside to expose the latent form of carnitine palmitoyltransferase (CPT-II), suggesting that the inhibition was specific for CPT-I [12].
• Since carnitine-dependent fatty acid oxidation is modulated by insulin in a variety of tissues, the effects of 1.7 microM insulin on the mitochondrial enzyme(s), carnitine palmitoyltransferase (malonyl-CoA-sensitive CPT-I and the matrix-facing CPT-II), were studied in neonatal rat cardiac myocytes cultured in the absence of serum [13].
• CPT-I activity in the insulin-supplemented, serum-free cultures is 57% higher (P < 0.002) than CPT-I activity in cells cultured in the absence of insulin; CPT-II activity is also significantly increased (P < 0.01) in the presence of insulin [13].
• In the cardiac cells treated with 5 microM digitonin, CPT-II contamination of CPT activity is 0.62% as quantitated by citrate synthase activity present in damaged myocytes under assay conditions [14].
• Our objective was to isolate from rat liver mitochondria the malonyl-CoA-regulated and detergent-labile enzyme, carnitine palmitoyltransferase I (CPT I), whose properties and relationship to CPT II have been the subject of debate [15].

Associations of Cpt2 with chemical compounds

• It has been reported that sodium cholate can separate the catalytic component of carnitine palmitoyltransferase-I (CPT-I) from a putative malonyl-CoA-binding regulatory protein capable of conferring sensitivity to malonyl-CoA on CPT-II [16].
• The CoA ester of the monocarboxylic 3-thia fatty acid, tetradecylthioacetic acid, which accumulates in the liver after administration, inhibited the CPT-I activity in vitro, but not that of CPT-II [17].
• This opens the possibility that mitochondrial HMG-CoA synthase and CPT-II retain some control of ketone body formation [17].
• CPT-II activity correlated with both palmitoyl-CoA and palmitoyl-L-carnitine oxidation in rats treated with different chain-length 3-thia fatty acids [18].
• Palmitoyl-L-carnitine oxidation and CPT-II activity were, however, unchanged after either EPA treatment or starvation [18].

Regulatory relationships of Cpt2

• The tetradecanamidomethyl analogue of (2R,6S)-1 activated CPT-I but inhibited CPT-II [19].

Other interactions of Cpt2

• CPT-II activity increases significantly only at very high insulin concentrations (1.7 microM), suggesting a role for insulin-like growth factor pathway [13].
• The expression of protein (by Western blotting) and mRNA (by semi-quantitative polymerase chain reaction) of the enzymes of the carnitine palmitoyltransferase system (CPT I and CPT II) and of liver fatty-acid-binding protein (L-FABP) was studied [3].
• They were identified as carnitine palmitoyltransferase 2, mitochondrial acyl-CoA thioesterase 1, isocitrate dehydrogenase 3 (NAD+) alpha, fumarate hydratase 1 and pyruvate dehydrogenase beta [20].

Analytical, diagnostic and therapeutic context of Cpt2

• The rCPT-II was found to be: (1) similar in size to the native rat liver enzyme (approximately 70 kDa) as judged by SDS/PAGE; (2) immunoreactive with a polyclonal serum raised against rat liver CPT-II; and (3) not glycosylated [1].
• A partially purified CPT II fraction from rat liver mitochondria was shown to be able to convert 3-hydroxypalmitoyl-CoA to 3-hydroxypalmitoylcarnitine, which could be identified by fast-atom-bombardment mass spectrometry [21].
• Perfusion with POCA selectively inhibited the activity of carnitine palmitoyltransferase 1, but had no influence on the activities of carnitine palmitoyltransferase 2, pyruvate dehydrogenase, and triglyceride lipase [22].
• To test whether additional contractile activity would make CPT II mRNA even higher, continuous indirect electrical stimulation was imposed on the tibialis anterior muscles [23].

References