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

Human carnitine palmitoyltransferase (CPT) deficiency results in 2 clinical forms: a more common "muscular form" with myoglobinuria with or without delayed or impaired ketogenesis and a rare "hepatic form" with hypoketotic hypoglycemia, encephalopathy and seizures without muscular manifestations. We present 2 patients, a male (patient 1) and a female (patient 2) with infantile "hepatic" CPT deficiency and previously documented CPT1 deficiency in fibroblasts. In patient 2, a deficiency of "total" CPT activity in liver had also been previously documented. We set up an isotope exchange assay system that effectively differentiated CPT1 and CPT2 activities in muscle. We found normal CPT1 and CPT2 activities in our patients under near saturating substrate conditions. The CPT1 and CPT2 activities were suppressed to a strikingly similar degree under different kinetic conditions as compared to control muscle and were found to have similar Km values for carnitine and PCoA. With Km concentrations of carnitine, the mean residual activities of CPT1 for patients 1 and 2 were 49 and 44%, respectively (control range 40-53%); the mean residual activities of CPT2 were 60 and 46%, respectively (control range 49-59%). With Km concentrations of PCoA, the mean residual activities of CPT1 for patients 1 and 2 were 52 and 58%, respectively (control range of 52-59%); mean residual activities of CPT2 were 54% and 56%, respectively (control range of 51-68%). When the Vmax concentration of PCoA was doubled and bovine serum albumin reduced to 0.1%, the mean residual activities of CPT1 for patients 1 and 2 were 69 and 63%, respectively (control range 60-80%). In "muscular" patients, a marked absolute deficiency of CPT2 activity (less than 12% residual) was found with an apparent increased sensitivity to suppression of enzymatic activity when the Km concentration of carnitine was used. We suggest that CPT1 and CPT2 may be separate proteins. Furthermore, CPT1 itself may exist as tissue-specific isoforms being the same protein in liver and fibroblasts and a different protein in muscle. Either could be encoded for by the same or closely related genes.
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PMID:Normal muscle CPT1 and CPT2 activities in hepatic presentation patients with CPT1 deficiency in fibroblasts. Tissue specific isoforms of CPT1? 280 20

Human carnitine palmitoyl transferase (CTP) deficiency results in two different clinical variants, one with "hepatic" and one with "muscular" symptoms. We studied CPT activity and long-chain fatty acid oxidation in fibroblast cell lines from four patients, two from each group. Overall CPT activity was deficient in patients' fibroblasts with the hepatic presentation, as previously demonstrated in patients' fibroblasts with the muscular presentation. The hepatic patients' fibroblasts displayed a CPT1 deficiency which resulted in impaired long-chain fatty acid oxidation. In contrast, CPT1 activity and palmitate oxidation were normal in muscular patients' fibroblasts. In these latter patients, the mutation presumably involved CPT2 activity. These data suggest that CPT deficiency is due to at least two different mutations, resulting in two distinct patterns of clinical and biochemical abnormalities.
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PMID:Hepatic and muscular presentations of carnitine palmitoyl transferase deficiency: two distinct entities. 321 16

Mitochondrial fatty acid oxidation (FAO) disorders are caused by defects in one of the FAO enzymes that regulates cellular uptake of fatty acids and free carnitine. An in vitro probe acylcarnitine (IVP) assay using cultured cells and tandem mass spectrometry is a tool to diagnose enzyme defects linked to most FAO disorders. Extracellular acylcarnitine (AC) profiling detects carnitine palmitoyltransferase-2, carnitine acylcarnitine translocase, and other FAO deficiencies. However, the diagnosis of primary carnitine deficiency (PCD) or carnitine palmitoyltransferase-1 (CPT1) deficiency using the conventional IVP assay has been hampered by the presence of a large amount of free carnitine (C0), a key molecule deregulated by these deficiencies. In the present study, we developed a novel IVP assay for the diagnosis of PCD and CPT1 deficiency by analyzing intracellular ACs. When exogenous C0 was reduced, intracellular C0 and total AC in these deficiencies showed specific profiles clearly distinguishable from other FAO disorders and control cells. Also, the ratio of intracellular to extracellular C0 levels showed a significant difference in cells with these deficiencies compared with control. Hence, intracellular AC profiling using the IVP assay under reduced C0 conditions is a useful method for diagnosing PCD or CPT1 deficiency.
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PMID:Intracellular in vitro probe acylcarnitine assay for identifying deficiencies of carnitine transporter and carnitine palmitoyltransferase-1. 2314 7