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)

Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle.
 ...
PMID:Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia. 17 5

Washed human spermatozoa had an endogenous oxygen uptake of 2.14 +/- 0.17 nmol O2/10(8) spermatozoa/min (mean +/- s.e..m., n = 35) which was stimulated by succinate (Vmax = 9.64 +/- 0.44 nmol O2/10(8) spermatozoa/min) but not by other substrates. The ATP concentration in freshly washed spermatozoa was 12.18 +/- 0.54 (s.e.m.) nmol/10(8) spermatozoa (n = 26) and was maintained for 2 h in the presence of 2 mM-D-glucose but fell to 9.56 +/- 0.73 (s.e.m.) nmol/10(8) spermatozoa (n = 13) in its absence. The presence of 2 microM-antimycin A, 2 microM-rotenone, 0.4 microM-carbonyl cyanide m-chlorophenyl hydrazone or 8 microM-oligomycin caused the ATP concentration to fall to less than 2 nmol/10(8) spermatozoa but their effect was partly alleviated by 2 mM-glucose. Sodium malonate (5 mM) prevented the stimulation of respiration by succinate but had no effect on the ATP concentration of the spermatozoa or their ability to produce 14CO2 from [U-14C]glucose. The least active of the tricarboxylic acid cycle enzymes was 2-oxoglutarate dehydrogenase (EC 1.2.4.2) (3.1 +/- 0.6 (s.e.m.) nmol substrate transformed/10(8) spermatozoa/h (n = 4). Cytochrome c oxidase (EC 1.9.3.1) was much less active than in rat spermatozoa (22.3 +/- 6.0 (s.e.m., n = 4) and 615 +/- 87 (n = 4) nmol transformed/10(8) spermatozoa/min). It is concluded that human spermatozoa can obtain ATP by the respiration of endogenous substrate but the substrates and metabolic pathways involved remain obscure.
 ...
PMID:The role of oxidative phosphorylation in the generation of ATP in human spermatozoa. 727 30

We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by approximately 50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain alpha-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c(1), and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13.
 ...
PMID:A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13. 1115 34

Studies with isolated mitochondria are performed at artificially high pO(2) (220 to 250 microM oxygen), although this condition is hyperoxic for these organelles. It was the aim of this study to evaluate the effect of hypoxia (20-30 microM) on the calcium-dependent activation of 2-oxoglutarate dehydrogenase (or 2-ketoglutarate dehydrogenase; OGDH) and mitochondrial nitric-oxide synthase (mtNOS). Mitochondria had a P/O value 15% higher in hypoxia than that in normoxia, indicating that oxidative phosphorylation and electron transfer were more efficiently coupled, whereas the intramitochondrial free calcium concentrations were higher (2-3-fold) at lower pO(2). These increases were abrogated by ruthenium red indicating that the higher uptake via the calcium uniporter was involved in this process. Mitochondria at high calcium concentration microdomains may produce nitric oxide, given the K(0.5) of calcium for OGDH (0.16 microM) and mtNOS (approximately 1 microM). Nitric oxide, by binding to cytochrome oxidase in competition with oxygen, decreases the rate of oxygen consumption. This condition is highly beneficial for the following reasons: i, these mitochondria are still able to produce ATP and support calcium clearance; ii, it prevents the accumulation of ROS by slowing the rate of oxygen consumption (hence ROS production); iii, the onset of anoxia is delayed, allowing oxygen to diffuse back to these sites, thereby ameliorating the oxygen gradient between regions of high and low calcium concentration. In this way, oxygen depletion at the latter sites is prevented. This, in turn, assures continued aerobic metabolism which may involve the activated dehydrogenases.
 ...
PMID:Differential requirements of calcium for oxoglutarate dehydrogenase and mitochondrial nitric-oxide synthase under hypoxia: impact on the regulation of mitochondrial oxygen consumption. 1597 65

Reactive oxygen species may contribute to the pathogenesis of muscular dystrophy. High intensity exercise clearly induces muscle damage in mdx mice; however, the effects of low intensity exercise training (LIT) on mdx muscle are less clear. We examined the effect of LIT on markers of oxidative stress (malondialdehyde and protein carbonyls), antioxidant (superoxide dismutase, catalase, and glutathione peroxidase), and mitochondrial (2-oxoglutarate dehydrogenase and cytochrome oxidase) enzymes in skeletal muscle of mdx and wild-type mice. Mdx and wild-type mice were allocated to LIT and sedentary groups. Malondialdehyde levels were higher in white muscle from sedentary mdx as compared to both sedentary and LIT wild-type mice (P<0.001). Protein carbonyl content was higher in white and red muscle of mdx versus wild-type mice (P<0.05). LIT was associated with lower levels of malondialdehyde and protein carbonyls in white muscle of mdx mice (decreased 38 and 44%, P<0.001 and P<0.01, respectively). Antioxidant and mitochondrial enzyme activities were higher in white muscle of mdx than in wild-type mice (P<0.05). LIT in mdx mice induced physiological adaptation resulting in lower levels of markers of oxidative stress that were not different than those from wild type. These results are of relevance for therapeutic exercise in patients with dystrophinopathy where exercise prescription remains controversial.
 ...
PMID:Low intensity training decreases markers of oxidative stress in skeletal muscle of mdx mice. 1756 Nov 3