Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin increases the synthesis of mitochondrial proteins in the isolated perfused heart and total cell protein synthesis in neonatal cardiac myocytes. 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. Following incubation in serum-free medium, there is a four-fold increase in the I50 of CPT-I for malonyl-CoA (3.8 microM) compared to cells cultured in serum-free medium to which insulin has been added (I50 = 0.8 microM). 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. Since CPT-II is an inner membrane protein, the CPT response to insulin may be coordinately regulated with other mitochondrial activities. Similar to CPT, cytochrome oxidase activity of cardiac myocytes in serum-free medium is increased 33% by insulin. Consistent with this finding, both CPT-II and cytochrome oxidase mRNA expression is elevated over control in the presence of insulin. CPT-II activity increases significantly only at very high insulin concentrations (1.7 microM), suggesting a role for insulin-like growth factor pathway. When myocytes are cultured in the presence of 1.7 microM insulin and then transferred to an insulin-free medium, subsequent addition of insulin does not stimulate uptake of deoxyglucose. These results suggest that the response of CPT to insulin is mediated by insulin-like growth factor activity and not by cellular glucose availability. The response of CPT to insulin does not appear to be mediated by the protein kinase C pathway since CPT-II activity is not reduced by the protein kinase C inhibitor, chelerythrine. Insulin significantly increases protein synthesis in the neonatal cardiac myocyte and in isolated mitochondria by increasing incorporation of labelled amino acid into total myocyte and/or mitochondrial protein. The degradation rate of radiolabelled protein in cardiac myocytes cultured in the presence of insulin is not different from that of insulin-deprived cells. The data suggest that insulin can affect the activity and expression of mitochondrial proteins, e.g., CPT, through the insulin-like growth factor-I pathway in neonatal cardiac myocytes.
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PMID:Insulin-associated changes in carnitine palmitoyltransferase in cultured neonatal rat cardiac myocytes. 776 Mar 80

The metabolic properties of brown adipose tissue (BAT), liver, and skeletal muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of type II diabetes) to test whether the severe insulin resistance of obese animals is specifically associated with a thermogenic defect in BAT. The respiratory response of brown adipocytes to norepinephrine and to agents bypassing the adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by two-thirds in obese rats, thereby indicating the presence of a major postreceptor defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT thermogenic capacity) were also decreased by two-thirds. The specific activities of these parameters expressed per total BAT mitochondrial protein were not altered either. This indicates that the total number of mitochondria per cell is decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase activity, protein content, and DNA content all increased by two to three times in the liver of obese SHR/N-cp rats, but these parameters remained unchanged in skeletal muscles (vastus lateralis and soleus). Such a remarkable liver hypertrophy may have occurred as a consequence of the persistent hyperphagia-hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte polyploidization. This observation together with the fact that daily energy expenditure associated with food intake was markedly increased in obese rats (representing as much as 25% of the total energy expenditure) strongly suggests that the liver plays a major role in energy balance in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats. 827 28

The antihyperglycaemic agent metformin (dimethylbiguanide) increases metabolic energy expenditure. The possibility that this might involve increased fuel utilization by brown adipose tissue (BAT) was studied. Basal and noradrenaline-stimulated (10(-6) mol/L) oxygen consumption by isolated brown adipocytes from normal and streptozotocin diabetic mice was unaffected by incubation with metformin (10(-4) mol/L) for 30 min. Basal and insulin-stimulated (10(-8) and 10(-6) mol/L) aerobic and anaerobic glucose metabolism was also unaffected during 2 hr incubations of BAT with metformin (10(-4) mol/L). Treatment of normal mice with metformin (250 mg/kg/day) for 7 days did not significantly alter the amount or cytochrome oxidase activity of BAT, and a preliminary semi-quantitative estimation of mitochondrial uncoupling protein showed no apparent change. The results suggest that metformin does not increase energy expenditure of brown adipose tissue.
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PMID:Metformin does not increase energy expenditure of brown fat. 838 71

This study compared the effects of aerobic exercise training and chronic administration of the selective beta 2-adrenergic agonist clenbuterol on whole body and skeletal muscle insulin resistance in obese (fa/fa) Zucker rats. Obese rats were randomly assigned to training, clenbuterol, or sedentary control groups. Lean littermates served as a second control group. After 4-5 wk of treatment, an oral glucose tolerance test was performed, followed 1 wk later by hindlimb perfusion, during which time the rates of glucose uptake and 3-O-methyl-D-glucose (3-MG) transport were assessed in the presence of a submaximal (500 microU/ml) insulin concentration. Training resulted in a significant increase in citrate synthase and cytochrome oxidase activity in the recruited muscles. Clenbuterol induced a large increase in muscle mass but provoked a significant decrease in oxidative enzyme activity and beta-adrenergic receptor density. Both treatments increased glucose tolerance and reduced the postglucose insulin response, with the improvements being more pronounced in the clenbuterol group. However, only exercise training improved insulin-stimulated hindlimb muscle glucose uptake (11.37 +/- 0.65, 8.73 +/- 0.77, and 8.27 +/- 0.41 mumol.g-1.h-1 for trained, clenbuterol, and sedentary control groups, respectively) and 3-MG transport. These results suggest that aerobic exercise training attenuated the insulin-resistant condition in the obese Zucker rat by a mechanism other than or in addition to beta 2-adrenergic receptor activation.
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PMID:Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats. 838 91

A condition similar to insulin-dependent diabetes mellitus (IDDM) was induced in male CD-1 mice by injection of streptozotocin (STZ). Five weeks after treatment, the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were isolated for analysis. Phosphorous metabolites were quantified by 31P-NMR and HPLC, native myosin was characterized electrophoretically, and activities of metabolic enzymes were measured spectrophotometrically. Relative to control animals, STZ-diabetes resulted in a significant 32% decrease in the FM1 isoform of myosin in EDL and a 24% decrease in IM myosin of SOL. Mass-specific activities of phosphofructokinase, citrate synthase, and cytochrome oxidase were significantly lower in SOL from STZ-diabetic mice than in controls by 23, 18, and 36%, respectively. Intracellular ATP was significantly lower in SOL from STZ-diabetic mice than in controls (3.44 +/- 0.20 mumol g-1 wet weight vs. 4.61 +/- 0.20 mumol g-1, respectively), as was creatine phosphate (11.98 +/- 0.80 mumol g-1 wet weight vs. 14.22 +/- 0.44 mumol g-1). In contrast to results from SOL, there were no significant changes in phosphorus metabolites or enzyme activity in EDL. These results show that the effects of IDDM on levels of phosphorus containing metabolites and maximal activities of key regulatory enzymes in muscle are markedly fiber-type specific. It is suggested that the muscle type-specific effects of STZ-diabetes may be a consequence of differential accumulation of intracellular fatty acids.
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PMID:Responses of mouse fast and slow skeletal muscle to streptozotocin diabetes: myosin isoenzymes and phosphorous metabolites. 859 19

The mitochondrial carnitine palmitoyltransferase (CPT) system is composed of two proteins, CPT-I and -II, which, together with carnitine acylcarnitine translocase, are involved in the transport of fatty acids into the mitochondrial matrix for beta-oxidation. In the liver, CPT-I and its inhibition by malonyl-CoA are sensitive to hormonal (10(-9) M) levels of insulin; however, a similar effect of insulin on heart CPT is controversial. In cultured neonatal rat cardiac myocytes, tissue culture concentrations (1.7 microM) of insulin increase CPT and cytochrome oxidase activities as well as mitochondrial protein synthesis, suggesting that a growth mechanism may be involved. Because insulin at high concentrations may interact with the insulin-like growth factor (IGF-I) receptor, the consequences of insulin's action on heart cells in culture may be mediated through the IGF pathway. Consistent with an IGF-mediated pathway for the effect of insulin, incorporation of radioactivity into immunoprecipitated CPT-II from insulin-treated cardiac myocytes is dramatically increased over control cells. The amount of immunoreactive CPT-I is also increased in insulin-treated cells. Moreover, an IGF-I analogue that inhibits the autophosphorylation of the IGF-I receptor blunts the insulin-mediated increase in CPT-I and -II activities by > 70%. At low physiologically relevant concentrations (10 ng/ml), IGF-I significantly increases the activities of both CPT-I and -II, and the IGF-I analogue eliminates the IGF-I response. This is the first study to suggest involvement of the IGF-I pathway in the regulation of mitochondrial CPT synthesis and activities in the heart.
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PMID:Increased carnitine palmitoyltransferase in cardiac myocytes is mediated by insulin growth factor I. 877 79

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.
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PMID:Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure. 892 17

TlpA, the membrane-anchored, thioredoxin-like protein from Bradyrhizobium japonicum, is essential for cytochrome aa3 biogenesis. The periplasmic domain of TlpA was previously shown to have protein thiol:disulfide oxidoreductase activity and reducing properties similar to those of cytoplasmic thioredoxins. Here, we replaced the proline-109 in its active-site sequence C107 V108 P109 C110 by a histidine residue. The resulting active-site motif (CVHC) resembles that of oxidizing thiol:disulfide oxidoreductases such as protein disulfide isomerase (PDI) and DsbA. Indeed, the TlpA variant P109H was by 66 mV more oxidizing than the wild-type protein. Nevertheless, the altered protein was even more efficient in catalyzing the reduction of insulin disulfides by dithiothreitol than the wild-type due to a faster recycling of its catalytically active, reduced form. Cells of B. japonicum expressing only the mutated tlpA gene had the same phenotypes as wild-type cells, suggesting that the change in the redox potential of TlpA was not critical for its in vivo function.
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PMID:Replacement of Pro109 by His in TlpA, a thioredoxin-like protein from Bradyrhizobium japonicum, alters its redox properties but not its in vivo functions. 913 95

The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes. Because non-insulin-dependent diabetes mellitus (NIDDM) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese, the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM. Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean (L) and eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [phosphofructokinase, glyceraldehyde phosphate dehydrogenase, hexokinase (HK)] and oxidative pathways [citrate synthase (CS), cytochrome-c oxidase], as well as for a glycogenolytic enzyme (glycogen phosphorylase) and a marker of anaerobic ATP resynthesis (creatine kinase). Insulin sensitivity was measured by using the euglycemic clamp technique. Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum velocity for oxidative enzymes (CS, cytochrome-c oxidase) was lowest in subjects with NIDDM. The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity. The HK/CS ratio had the strongest correlation (r = -0.60, P < 0.01) with insulin sensitivity. In summary, an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects. The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance.
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PMID:Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. 921 60

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
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PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94


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