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)

A complete pathway for Azorhizobium caulinodans nicotinate catabolism has been determined from mutant phenotype analyses, isolation of metabolic intermediates, and structural studies. Nicotinate serves as a respiratory electron donor to O2 via a membrane-bound hydroxylase and a specific c-type cytochrome oxidase. The resulting oxidized product, 6-hydroxynicotinate, is next reduced to 1,4,5,6-tetrahydro-6-oxonicotinate. Hydrolytic ring breakage follows, with release of pyridine N as ammonium. Decarboxylation then releases the nicotinate C-7 carboxyl group as CO2, and the remaining C skeleton is then oxidized to yield glutarate. Transthioesterification with succinyl coenzyme A (succinyl-CoA) yields glutaryl-CoA, which is then oxidatively decarboxylated to yield crotonyl-CoA. As with general acyl beta oxidation, L-beta-hydroxybutyryl-CoA, acetoacetyl-CoA, and finally two molecules of acetyl-CoA are produced. In sum, nicotinate is catabolized to yield two CO2 molecules, two acetyl-CoA molecules, and ammonium. Nicotinate catabolism stimulates Azorhizobium N2 fixation rates in culture. Nicotinate catabolism mutants still able to liberate pyridine N as ammonium retain this capability, whereas mutants so blocked do not. From, mutant analyses and additional physiological tests, N2 fixation stimulation is indirect. In N-limited culture, nicotinate catabolism augments anabolic N pools and, as a consequence, yields N2-fixing cells with higher dinitrogenase content.
 ...
PMID:Elucidation of the complete Azorhizobium nicotinate catabolism pathway. 144 45

Histochemical evidence of the activity and distribution of glycolysis redox enzymes, tissue respiration and terminal oxidation pattern (dehydrogenase of lactic, malic, succinic and isocitric acids, NAD-N- and NADPh-N-ase, cytochrome oxidase) as well as the levels of the major carbohydrates (glycogen, neutral aminopolysaccharides, glucose) were experimentally studied in the cardiomyocytes of myocardial necrotic, perinecrotic and intact areas in the control and in the experimental material under the administration of terrilitin-nicotinic acid mixture. It was stated that the use of aforementioned mixture contributed to the retention of enzymatic activity and optimal levels of energy formation in the cardiomyocytes of the marginal infarction zone and noticeably prevented the destructive involvement of the considered area as well as the impairment of functional activity of oscillating cardiomyocytes. Therefore, the application of the mixture improved the outcome prognosis in acute myocardial infarction.
 ...
PMID:[The structuro-functional state of the ischemic myocardium under the action of a terrilitin-nicotinic acid mixture in animal experiments]. 245 88

Haidle, C. W. (The University of Texas, Austin), and R. Storck. Control of dimorphism in Mucor rouxii. J. Bacteriol. 92:1236-1244. 1966.-Yeastlike cells of Mucor rouxii NRRL 1894 were converted to filaments in a medium containing glucose, mineral salts, casein hydrolysate, nicotinic acid, and thiamine when the gas phase was changed from CO(2)-N(2) or N(2) alone to air. Germ tubes began to appear 3 to 4 hr after exposure to air. Ribonucleic acid (RNA) precursors were incorporated into RNA in a discontinuous fashion during this conversion, but the incorporation was continuous during the anaerobic growth of yeastlike cells and during the aerobic germination of sporangiospores. The incorporation of labeled amino acids during the conversion was exponential. Labeling of ribosomal RNA occurred as shortly as 5 min after replacement of CO(2)-N(2) with air. However, P(32)-labeled RNA isolated 20 min after exposure to air had a guanine plus cytosine (GC) content of 41% (mole%) as compared with the 47% found for labeled and unlabeled RNA isolated at other stages of the life cycle of this organism or later during the conversion. In addition, the overall base composition of this 20-min pulse-labeled RNA resembled that of deoxyribonucleic acid (GC = 39%), suggesting that a significant proportion of this RNA is of the messenger type. Furthermore, the synthesis of cytochrome oxidase was induced upon exposure of yeastlike cells to air. Cyanide, acriflavine, and cycloheximide, which inhibited the action or synthesis of cytochrome oxidase, also inhibited the yeast to filament transition.
 ...
PMID:Control of dimorphism in Mucor rouxii. 428 98

The effects of increasing mitochondrial oxidative phosphorylation (OXPHOS), by enhancing electron transport chain components, were evaluated on 1-methyl-4-phenylpyridinium (MPP+) toxicity in brain neuroblastoma cells. Although glucose is a direct energy source, ultimately nicotinamide and flavin reducing equivalents fuel ATP produced through OXPHOS. The findings indicate that cell respiration/mitochondrial O(2) consumption (MOC) (in cells not treated with MPP+) is not controlled by the supply of glucose, coenzyme Q(10) (Co-Q(10)), NADH+, NAD or nicotinic acid. In contrast, MOC in whole cells is highly regulated by the supply of flavins: riboflavin, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), where cell respiration reached up to 410% of controls. In isolated mitochondria, FAD and FMN drastically increased complex I rate of reaction (1300%) and (450%), respectively, having no effects on complex II or III. MPP+ reduced MOC in whole cells in a dose-dependent manner. In isolated mitochondria, MPP+ exerted mild inhibition at complex I, negligible effects on complexes II-III, and extensive inhibition of complex IV. Kinetic analysis of complex I revealed that MPP+ was competitive with NADH, and partially reversible by FAD and FMN. Co-Q(10) potentiated complex II ( approximately 200%), but not complex I or III. Despite positive influence of flavins and Co-Q(10) on complexes I-II function, neither protected against MPP+ toxicity, indicating inhibition of complex IV as the predominant target. The nicotinamides and glucose prevented MPP+ toxicity by fueling anaerobic glycolysis, evident by accumulation of lactate in the absence of MOC. The data also define a clear anomaly of neuroblastoma, indicating a preference for anaerobic conditions, and an adverse response to aerobic. An increase in CO(2), CO(2)/O(2) ratio, mitochondrial inhibition or O(2) deprivation was not directly toxic, but activated metabolism through glycolysis prompting depletion of glucose and starvation. In conclusion, the results of this study indicate that the mechanism of action for MPP+, involves the inhibition of complex I and and more specifically complex IV, leading to impaired OXPHOS and MOC. Moreover, flavin dervatives control the rate of complex I/cellular respiration and Co-Q10 augments complex II [corrected].
 ...
PMID:Effects of enhancing mitochondrial oxidative phosphorylation with reducing equivalents and ubiquinone on 1-methyl-4-phenylpyridinium toxicity and complex I-IV damage in neuroblastoma cells. 1500 52

Heme, the major functional form of iron, is synthesized in the mitochondria. Although disturbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation, all of which are hallmarks of ageing, heme has been little studied in nutritional deficiency, in ageing, or age-related disorders such as Alzheimer's disease (AD). Biosynthesis of heme requires Vitamin B(6), riboflavin, biotin, pantothenic acid, and lipoic acid and the minerals zinc, iron, and copper, micronutrients are essential for the production of succinyl-CoA, the precursor for porphyrins, by the TCA (Krebs) cycle. Only a small fraction of the porphyrins synthesized from succinyl-CoA are converted to heme, the rest are excreted out of the body together with the degradation products of heme (e.g. bilirubin). Therefore, the heme biosynthetic pathway causes a net loss of succinyl-CoA from the TCA cycle. The mitochondrial pool of succinyl-CoA may limit heme biosynthesis in deficiencies for micronutrients (e.g. iron or biotin deficiency). Ageing and AD are also associated with hypometabolism, increase in heme oxygenase-1, loss of complex IV, and iron accumulation. Heme is a common denominator for all these changes, suggesting that heme metabolism maybe altered in age-related disorders. Heme can also be a prooxidant: it converts less reactive oxidants to highly reactive free radicals. Free heme has high affinity for different cell structures (protein, membranes, and DNA), triggering site-directed oxidative damage. This review discusses heme metabolism as related to metabolic changes seen in ageing and age-related disorders and highlights the possible role in iron deficiency.
 ...
PMID:Heme, iron, and the mitochondrial decay of ageing. 1523 Dec 38