Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type II carnitine palmitoyltransferase deficiency is the most common cause of exercise-induced rhabdomyolysis, myoglobinuria, and proximal muscle weakness and pain in young adults. A lack of this enzyme impairs mitochondrial oxidation of long-chain fatty acids and can lead to rhabdomyolysis, myoglobinuria, and renal failure. Carnitine palmitoyltransferase deficiency, unusual but not rare, is often detected by finding elevated creatine phosphokinase level in a routine blood chemistry panel. A case of carnitine palmitoyltransferase deficiency in a college athlete is presented, and the disorder is compared with defective myophosphorylation in McArdle's disease, the next most frequent cause of similar symptoms.
J Am Coll Health 1995 Sep
PMID:Carnitine palmitoyltransferase deficiency in a college athlete: a case report and literature review. 759 92

We describe neonatal onset of a lethal multiorgan deficiency of carnitine palmitoyltransferase II (CPT II) associated with dysmorphic features, cardiomyopathy, and cystic dysplasia of the brain and kidneys. Concentrations of long-chain acylcarnitines were evaluated in blood and multiple tissues, diffuse lipid accumulation was present at autopsy, and a profound deficiency of CPT II activity was evident in heart, liver, muscle, and kidney tissue. This disorder constitutes another recognizable malformation syndrome with a metabolic basis. Deficiency of CPT II should be included in the differential diagnosis of patients with cystic renal dysplasia, dysmorphism, central nervous system malformations, and early death, along with glutaric acidemia type II, Zellweger syndrome, and other disorders in which peroxisomal beta-oxidation is impaired. The clinicopathologic similarities among these disorders raise the possibility that a common biochemical mechanism, namely the disruption of beta-oxidation of fatty acids, is responsible for the abnormal organogenesis.
J Pediatr 1995 Sep
PMID:Lethal neonatal deficiency of carnitine palmitoyltransferase II associated with dysgenesis of the brain and kidneys. 765 72

The synthesis and pharmacological activity of a series of terbenzimidazoles are described. The ability of these derivatives to induce DNA cleavage in the presence of topoisomerase I was evaluated in vitro. These analogs were also assayed for their cytotoxicity in RPMI 8402 cells and the camptothecin-resistant CPT-K5 cells. In addition the potential for these compounds to serve as substrates for MDR1 was also determined. Several terbenzimidazoles exhibited similar cytotoxicity against variants of human tumor cells that either overexpress MDR1 or are camptothecin-resistant.
J Med Chem 1995 Sep 01
PMID:Synthesis and evaluation of terbenzimidazoles as topoisomerase I inhibitors. 765 51

Acyl-coenzyme A (CoA) binding protein (ACBP) is a 10-kd protein that binds acyl-CoA moieties and stimulates medium-chain fatty acid synthesis by goat mammary gland fatty acid synthetase. Its exact role in intermediary lipid metabolism has not been fully elucidated. It is hypothesized that ACBP is directly involved in the metabolism of lipid. In the present study, purified rat liver ACBP was used to generate a polyclonal antisera for radioimmunoassay of ACBP in tissue specimens isolated from fasted rats and rats fed normal rat chow and a high-fat diet. In addition, purified ACBP was used to examine its effect on the activity of mitochondrial outer membrane (OM) carnitine palmitoyltransferase (CPT0). Fasting for 24 hours significantly decreased tissue levels of ACBP in the liver (69.0 +/- 7.2 v 46.7 +/- 5.0 pg/ng DNA), whereas feeding of a high-fat diet for 48 hours caused ACBP levels to increase (69.0 +/- 7.2 v 103.9 +/- 18.0). Hepatic levels of this protein continued to increase and remained elevated with prolonged exposure to the high-fat diet (28 days). A similar pattern of change was observed in the kidney, but the magnitude of change was less. Heart ACBP did not respond acutely to the high-fat diet, but did increase after prolonged exposure (28 days). Fasting had no effect on ACBP levels in kidney and heart. Addition of ACBP to an in vitro assay system significantly increased the activity of CPT0 (from 5.2 +/- 0.8 to 72.1 +/- 5.3 nmol palmitoylcarnitine formed.min-1.mg-1 protein) when measured under inhibiting concentrations of palmitoyl-CoA (40 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism 1995 Sep
PMID:Effects of high-fat diet and fasting on levels of acyl-coenzyme A binding protein in liver, kidney, and heart of rat. 766 93

We evaluated the stability of human immunodeficiency virus (HIV) load markers from blood samples collected in VACUTAINER CPT or standard VACUTAINER brand tubes using sodium heparin or sodium citrate as anticoagulants. Quantitative plasma culture and p24 antigen concentrations were determined, and HIV RNA levels in plasma were measured by both reverse transcription-PCR-enzyme-linked immunosorbent assay (RT-PCR-ELISA) and branched DNA methods. All tubes were stored at room temperature for analysis at 2, 24, 48, and 72 h after the blood samples were drawn. No difference was seen between tube types with respect to the HIV titer in plasma or the positivity rate for all samples that demonstrated a fall in titer over time. Unbound p24 antigen levels in plasma decreased during the initial 48-h period in both tube types. Immune complex-dissociated p24 antigen levels decreased in CPT tubes but not in standard VACUTAINER tubes. The HIV RNA copy number in plasma measured by RT-PCR-ELISA was stable in most subjects and was significantly higher in CPT tubes than in standard VACUTAINER tubes at 24 and 72 h after the blood samples were drawn. The branched DNA probe assay detected a significant decline in HIV RNA equivalent in plasma over 72 h in both collection tubes, the decline being more dramatic in the standard VACUTAINER tube than the CPT tube. Overall, interday variability suggests that samples collected for a particular assay should be processed at the same time after blood is drawn and that a particular tube type be used throughout a given study.
J Clin Microbiol 1994 Sep
PMID:Stabilities of quantitative plasma culture for human immunodeficiency virus, RNA, and p24 antigen from samples collected in VACUTAINER CPT and standard VACUTAINER tubes. 781 49

Rats treated orally for 21 days with aminocarnitine, an inhibitor of carnitine palmitoyltransferase-2 (CPT-2), do not show hypertrophy of the heart. This contrasts with the effects of carnitine palmitoyltransferase-1 (CPT-1) inhibitors, that, according to the literature, cause hypertrophy. 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. CPT-1 and CPT-2 inhibitors cause different metabolic changes in the heart. Electron microscopy of hearts fixed 1 hour after Langendorff perfusion with the two types of inhibitors reveals some of these changes. Multilamellar vesicles were observed with aminocarnitine (CPT-2 inhibitor) but not with etomoxir (CPT-1 inhibitor). When both inhibitors were present, electron-dense spots adjacent to mitochondria were observed, possibly containing long-chain acylaminocarnitine.
Cardioscience 1994 Sep
PMID:Comparison of the effects of carnitine palmitoyltransferase-1 and -2 inhibitors on rat heart hypertrophy. 782 56

Cephaloridine (Cld), the most widely studied nephrotoxic cephalosporin, has significant structural homology with carnitine, which facilitates the transport of long-chain fatty acids into the mitochondrial inner matrix. Because of this homology, and evidence of a role of lipids in cephaloglycin (Cgl) nephrotoxicity, protocols were designed to compare the effects of Cld and Cgl on renal cortical mitochondrial carnitine transport, on long-chain fatty acylcarnitine-mediated respiration and on the in situ mitochondrial pools and urinary excretion of carnitine and acylcarnitines. The following was found: 1) both cephalosporins reduced carnitine-facilitated pyruvate oxidation (CFPO) and palmitoylcarnitine-mediated respiration (PCMR) by 40 to 50% in mitochondria exposed in vivo (300 mg/kg b.wt., 1 hr). CFPO could be decreased by reduction of carnitine uptake, pyruvate oxidation or carnitine acetyltransferase activity; 2) neither cephalosporin reduced mitochondrial carnitine acetyltransferase or carnitine palmitoyltransferase; 3) with in vitro exposure (2000 micrograms/ml, immediate effect) Cgl had no significant toxicity to mitochondrial CFPO. Cld inhibited CFPO in a dose-dependent manner, up to 100% at 2000 micrograms/ml; this effect was reduced by increasing carnitine concentrations; 4) in vitro Cld prevented the potentiation of PCMR by preloading with carnitine, reduced mitochondrial acetylcarnitine/carnitine exchange by 70% and reduced PCMR by 30%; 5) in vivo Cld increased mitochondrial-free carnitine in the in situ kidney by 100%; and 6) in vivo Cld increased the fractional renal excretion of carnitine from 0 +/- 0 to 0.29 +/- 0.03 and the fractional excretion of long-chain acylcarnitines from 0.06 +/- 0.01 to 0.79 +/- 0.17.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1994 Sep
PMID:Toxicity of cephaloridine to carnitine transport and fatty acid metabolism in rabbit renal cortical mitochondria: structure-activity relationships. 793 99

The selective inhibition of individual carnitine acyltransferases may be useful in the therapy of diabetes and heart disease. Aminocarnitine (3) is a weak competitive inhibitor (K(i) = 4.0 mM) for carnitine acetyltransferase (CAT), although the N-acetyl derivative 4 is about 165 times more potent (K(i) = 0.024 mM) than 3. Compound 3 is also a potent competitive inhibitor for carnitine palmitoyltransferases 1 and 2 (CPT-1 and CPT-2) (IC50 for CPT-2 = 805 nM). We synthesized 3-amino-5,5-dimethylhexanoic acid (7) and its N-acetyl derivative (8) as isosteric analogs of 3 and 4 that lack the quaternary ammonium positive charge. Like 3 and 4, compounds 7 and 8 were competitive inhibitors of CAT with significantly different potencies, but in this case, 8 (K(i) = 25 mM) was 10 times less potent than 7 (K(i) = 2.5 mM). R-(-)-7 and S-(+)-7 were stereoselective inhibitors of CAT (K(i) = 1.9 and 9.2 mM, respectively). Racemic 7 was a weak competitive inhibitor of CPT-2 (K(i) = 20 mM) and had no effect on CPT-1. These results are consistent with differences among the carnitine-binding sites on carnitine acyl-transferases that may be useful in selective inhibitor design. Furthermore, the data suggest that the quaternary ammonium positive charge of carnitine may be important for the proper orientation of carnitine and its analogs in the binding site.
J Med Chem 1994 Sep 30
PMID:3-Amino-5,5-dimethylhexanoic acid. Synthesis, resolution, and effects on carnitine acyltransferases. 793 52

We have identified two partially overlapping genomic clones that contain part of the 5' regulatory region of the human carnitine palmitoyltransferase II gene. The 1.2 kb region upstream the transcription start site, as defined by primer extension experiments, shows promoter activity when inserted upstream of a reporter gene and contains a putative insulin responsive element.
Biochim Biophys Acta 1994 Sep 13
PMID:Identification of 5' regulatory regions of the human carnitine palmitoyltransferase II gene. 808 71

Fura 2 fluorescence measurements were carried out on microperfused rat cortical collecting ducts (CCD) to investigate the effect of adenosine 3',5'-cyclic monophosphate (cAMP) and adenylate cyclase-stimulating hormones on free cytosolic calcium ([Ca2+]i). Forskolin, 3-isobutyl-1-methylxanthine, and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) all triggered marked and sustained [Ca2+]i variations. Maximal increases elicited by 100 microM CPT-cAMP amounted to 101 +/- 11 nM (mean +/- SE, n = 18). This effect was mostly dependent on the presence of basolateral calcium and totally independent of luminal calcium. It remained unchanged in CCD perfused with sodium-free luminal fluid (82 +/- 10 nM, n = 5), pretreated with 1 mM bath ouabain (113 +/- 20, n = 4), or superfused with sodium-free bath in the presence of ouabain (82 +/- 22, n = 5). The V2 agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 10 nM) increased [Ca2+]i by 57 +/- 5 nM (n = 27), a value 40% lower than that achieved with 10 nM AVP (141 +/- 7, n = 34) but similar to that observed with AVP + a V1a antagonist (57 +/- 6, n = 6). Significant effects could also be obtained with 200 pM DDAVP (31 +/- 6, n = 8) and arginine vasopressin (AVP) (72 +/- 6, n = 16). Rat calcitonin also raised [Ca2+]i by 43 +/- 10 (n = 8) and 66 +/- 8 nM (n = 17) at 1 and 10 nM, respectively, and its effect was not additive to that of CPT-cAMP. Calcitonin and DDAVP effects, like those of CPT-cAMP and forskolin, were nearly abolished in Ca(2+)-free bath, but AVP action on intracellular release persisted. These results show that, in rat CCD, cAMP effects on [Ca2+]i mainly result from basolateral calcium entry. In contrast to rabbit CCD the mechanism is independent on Na reabsorption and basolateral Na+/Ca2+ exchange. Calcitonin and DDAVP effects on [Ca2+]i are probably secondary to increased cAMP production.
Am J Physiol 1994 Sep
PMID:cAMP-dependent effects of vasopressin and calcitonin on cytosolic calcium in rat CCD. 809 49


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