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)

Male mice carrying the spfash mutation have 5-10% of the normal activity of ornithine carbamoyltransferase, yet are only slightly hyperammonaemic and develop quite well. A study of liver mitochondria from normal and spfash males showed that they differ in important ways. (1) The spfash liver contains about 33% more mitochondrial protein per g than does normal liver. (2) The specific activities of carbamoyl-phosphate synthetase (ammonia) and glutamate dehydrogenase are about 15% lower than normal in mitochondria from spfash mice, whereas those of beta-hydroxybutyrate dehydrogenase and cytochrome oxidase are 22% higher and 30% lower respectively. (3) In the presence of 10 mM-ornithine and the substrates for carbamoyl phosphate synthesis, coupled and uncoupled mitochondria from spfash mice synthesize citrulline at unexpectedly high rates, about 25 and 44 nmol/min per mg respectively. Though these are somewhat lower than the corresponding rates obtained with normal mitochondria, the difference does not arise from the deficiency in ornithine carbamoyltransferase, but from the lower carbamoyl-phosphate synthetase activity of the mutant mitochondria. (4) At lower external [ornithine] (less than 2 mM), a smaller fraction of the carbamoyl phosphate synthesized is converted into citrulline in spfash than in normal mitochondria. These studies show that what appears to be a single mutation brings about major adaptations in the mitochondrial component of liver. In addition, they clarify the role of ornithine transport and of protein-protein interactions in citrulline synthesis in normal mitochondria.
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PMID:Altered enzyme activities and citrulline synthesis in liver mitochondria from ornithine carbamoyltransferase-deficient sparse-furash mice. 292 15

1. A lag period of about 4 days preceded the onset of metamorphosis precociously induced by tri-iodothyronine in tadpoles of the giant American bullfrog (Rana catesbeiana). It was established by the accelerated synthesis or induction of carbamoyl phosphate synthetase and cytochrome oxidase in the liver, serum albumin and adult haemoglobin in the blood, acid phosphatase in the tail, and the increase in the hindleg/tail length ratio. 2. A 4- to 6-fold stimulation, 2 days after the induction of metamorphosis, of the rate of synthesis of rapidly labelled nuclear RNA in liver cells was followed by an increasing amount of RNA appearing in the cytoplasm. Most of the newly formed RNA on induction of metamorphosis was of the ribosomal type. An accelerated turnover at early stages of development preceded a net accumulation of RNA in the cytoplasm, with no change in the amount of DNA per liver. 3. Most hepatic ribosomes of the pre-metamorphic tadpoles were present as 78s monomers and 100s dimers; metamorphosis caused a shift towards larger polysomal aggregates with newly formed ribosomes that were relatively more tightly bound to membranes of the endoplasmic reticulum. 4. The appearance of new polyribosomes in the cytoplasm on induction of metamorphosis was co-ordinated in time with a stimulation of synthesis of phospholipids of the smooth and rough endoplasmic reticulum, followed by a gradual shift in preponderance from the smooth to the rough type of microsomal membranes. 5. Electron- and optical-microscopic examination of intact hepatocytes revealed a striking change in the distribution and nature of ribosomes and microsomal membranes during metamorphosis. 6. Ribosomes prepared from non-metamorphosing and metamorphosing animals were identical in their sedimentation coefficients and in the structural ribosomal proteins. The base composition and sedimentation coefficients of ribosomal RNA were also identical. Induction of metamorphosis also did not alter the incorporation of (32)P into the different phospholipid constituents of microsomal membranes. 7. Nascent (14)C-labelled protein with the highest specific activity was recovered in the ;heavy' rough membrane fraction of microsomes, whereas little (14)C was associated with ;free' polysomes. Protein synthesis in vivo was most markedly stimulated during metamorphosis in the tightly membrane-bound ribosomal fraction after the appearance of new ribosomes. 8. The rate of synthesis of macromolecules in vivo could not be followed beyond 7-8 days after induction because of variable shifts in precursor pools due to regression of larval tissues. 9. The stimulation of RNA and ribosome formation was specifically associated with the process of metamorphosis since no similar response to thyroid hormones occurred in those species (Axolotl and Necturus) in which the hormones failed to induce metamorphosis.
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PMID:The formation, distribution and function of ribosomes and microsomal membranes during induced amphibian metamorphosis. 558 18

We examined the regulation of Neurospora crassa arg-2 and cpc-1 in response to amino acid availability.arg-2 encodes the small subunit of arginine-specific carbamoyl phosphate synthetase; it is subject to unique negative regulation by Arg and is positively regulated in response to limitation for many different amino acids through a mechanism known as cross-pathway control. cpc-1 specifies a transcriptional activator important for crosspathway control. Expression of these genes was compared with that of the cytochrome oxidase subunit V gene, cox-5. Analyses of mRNA levels, polypeptide pulse-labeling results, and the distribution of mRNA in polysomes indicated that Arg-specific negative regulation of arg-2 affected the levels of both arg-2 mRNA and arg-2 mRNA translation. Negative translational effects on arg-2 and positive translational effects on cpc-1 were apparent soon after cells were provided with exogenous Arg. In cells limited for His, increased expression of arg-2 and cpc-1, and decreased expression of cox-5, also had translational and transcriptional components. The arg-2 and cpc-1 transcripts contain upstream open reading frames (uORFs), as do their Saccharomyces cerevisiae homologs CPA1 and GCN4. We examined the regulation of arg-2-lacZ reporter genes containing or lacking the uORF start codon; the capacity for arg-2 uORF translation appeared critical for controlling gene expression.
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PMID:Translational regulation in response to changes in amino acid availability in Neurospora crassa. 756 72

The sparse fur (spf) mutant mouse, with an X-linked ornithine transcarbamylase deficiency, is a model of congenital hyperammonemia in children. Our earlier studies indicated a deficiency of hepatic carnitine, CoA-SH, acetyl CoA, and ATP in spf mice. We have now studied the effects of a 7-day treatment with acetyl-L-carnitine (ALCAR) in the spf/Y mice on the activity and expression of the respiratory chain enzyme cytochrome c oxidase (COX; EC 1.9.3.1). We found decreased hepatic activity and expression of COX in the untreated hyperammonemic spf/Y mice, which was restored upon ALCAR treatment. Because COX is a mitochondrial membrane protein, we also carried out studies to explain the mechanism of ALCAR through its effect on membrane stability. Our results indicate a decrease of the mitochondrial membrane cholesterol/phospholipid molar ratio (CHOL/PL ratio) with the activity and expression of COX in untreated spf/Y mice. While ALCAR treatment normalized the ratios, it also restored the hepatic ATP production to normal. To study further if there was any effect of ALCAR on the mitochondrial matrix urea cycle enzymes, we measured the activity and expression of mutant ornithine transcarbamylase (OTC; EC 2.1.3.3) and normal carbamyl phosphate synthase-I (CPS-I; EC 6.3.4.16) in spf/Y mice. There was no general effect on the specific activities of the matrix enzymes upon ALCAR treatment, although their mRNA levels were enhanced. Our studies point towards the feasibility of an ALCAR treatment in conjunction with other treatment modalities, e.g. sodium benzoate and/or arginine, to improve the availability of cellular ATP and to counteract the effects of hereditary hyperammonemic syndromes in children.
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PMID:Restoration of hepatic cytochrome c oxidase activity and expression with acetyl-L-carnitine treatment in spf mice with an ornithine transcarbamylase deficiency. 971 4

The first attempt to phylogenetically place Conopidae using molecular characters, as well as the largest molecular analysis of relationships within Schizophora (Diptera) to date, is presented. Twenty-eight taxa from 11 acalyptrate families and seven acalyptrate superfamilies are represented. Nearly 12,800 bp of sequence data from 10 genes representing both mitochondrial (cytochrome oxidase I (COI), cytochrome b (cytB), and 12S) and nuclear genes (28S, the carbamoyl phosphate synthetase region of CAD (CAD), elongation factor-1alpha (EF-1alpha), white, alanyl-tRNA synthetase (AATS), triose phosphate isomerase (TPI), and phosphogluconate dehydrogenase (PGD)) are analysed. Parsimony and Bayesian analyses strongly support the monophyly of both Conopidae and Schizophora. While in the parsimony analysis, Conopidae are placed as sister to the remaining Schizophora, the Bayesian analysis recovers a Conopidae+Lauxaniidae clade. The value of nuclear, mitochondrial, ribosomal, and protein-coding gene sequence data for answering phylogenetic questions at different levels of divergence is evaluated.
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PMID:Placement of Conopidae (Diptera) within Schizophora based on mtDNA and nrDNA gene regions. 2036 64