Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carnitine was administered to a group of patients in shock, and the activities of cytochrome oxidase and succinate cytochrome c reductase in muscle needle biopsies from these patients were compared to those activities present in a non-carnitine treated control group of patients. Carnitine seemingly exerted a significant protective action on cytochrome oxidase activity during the initial phases of shock, but not to such an extent on succinate cytochrome c reductase activities.
 ...
PMID:Effects of L-carnitine administration on mitochondrial electron transport activity present in human muscle during circulatory shock. 299 47

Skin fibroblast carnitine uptake studies may identify and differentiate primary and secondary carnitine deficiency disorders. To confirm the specificity of these studies in differentiating primary from secondary carnitine deficiency disorders, we have studied carnitine uptake in the cultured skin fibroblasts from 5 children who have various enzymatic defects in intramitochondrial beta-oxidation including short-chain, medium-chain and long-chain acyl-CoA dehydrogenase and short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiencies, and in 4 children with cytochrome oxidase deficiency. Carnitine uptake was normal in the intramitochondrial beta-oxidation cases, suggesting other mechanisms for their carnitine deficiency. Therefore, intramitochondrial beta-oxidation defects associated with carnitine deficiency can be differentiated from primary carnitine deficiency not only by the presence of an abnormal dicarboxylic aciduria but by normal skin fibroblast carnitine uptake. In contrast to these findings, carnitine uptake in the cultured skin fibroblasts of four children with secondary carnitine deficiency due to cytochrome oxidase deficiency demonstrated a partial decrease in the maximal velocity of uptake (20-47% control Vmax), similar to that observed in the primary carnitine deficiency heterozygotes. We propose that this observation may be due to a generalized decrease in intracellular ATP, thus decreasing the efficiency of the energy- and sodium-dependent carnitine transporter. We conclude that carnitine uptake studies in cultured skin fibroblasts will contribute to an understanding of the mechanisms of carnitine depletion in the primary and secondary carnitine deficiency disorders.
 ...
PMID:Skin fibroblast carnitine uptake in secondary carnitine deficiency disorders. 838 12

Carnitine is an essential cofactor for long-chain fatty acid oxidation. We characterized the human carnitine transporter in vitro in a cultured skin fibroblast model both at the previously established Km concentration of carnitine uptake in fibroblasts (5 mumol/liter) and at 0.05% Km (0.25 mumol/liter). A rapid exponential dose-dependent decrease in mean percentage of carnitine uptake was demonstrated with increasing concentrations of nigericin, but no significant decrease was found with equimolar amounts of valinomycin. This would suggest that the Na+ gradient is integral to carnitine transport function. Interference of the Na+ (out-in) gradient by nigericin may be secondary to cytoplasmic acidification by this K+ proton ionophore. The rate of uptake was fully saturated at an extracellular Na+ concentration of 150 mmol/liter. Replacement of 150 mmol/liter extracellular Na+ with Li+ resulted in an 80 and a 50% reduction, and replacement with K+ and Rb+ ions resulted in a 100 and an 85 to 90% reduction in carnitine uptake, respectively, at carnitine concentrations of 0.25 and 5 mumol/liter, underlining the specific requirement for the Na+ ion. The effects of different site-specific respiratory chain toxins, namely, rotenone (complex I), antimycin A (complex III), and potassium cyanide (KCN) (complex IV) on carnitine uptake was also examined. A rapid exponential dose-dependent decrease in mean percentage of carnitine uptake with increasing concentrations of inhibitors was demonstrated. These data suggest either a metabolic energy requirement of the carnitine transporter or interference of the Na+ (out-in) gradient by a proton gradient (in-out) secondary to the accumulation of intracellular H+ ions, due to the action of the respiratory chain toxins, further suggesting that the transporter is sensitive to and inhibited by intracellular H+ ions. The effects of several sulfhydryl-binding agents, namely 2,4-dinitrofluorobenzene, N-ethylmaleimide, and mersalyl acid, were examined, and a significant inhibition of carnitine uptake was demonstrated, suggesting that free sulfhydryl groups are also integral to the import function of the human fibroblast transporter.
 ...
PMID:Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts. 863 46

Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC.
 ...
PMID:[Metabolic intolerance to exercise]. 1283 48