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)

S phase entry, i.e. start of DNA replication, is a crucial step in proliferation. Inhibition of S phase entry correlates with inhibition of hypusine formation, an event affecting only the eukaryotic initiation factor 5A (eIF-5A). Its hypusine-containing sequence was postulated to authorize polysomal utilization of specific transcripts for proteins necessary to enable DNA replication. Using mimosine to reversibly suppress the hypusine-forming deoxyhypusyl hydroxylase (E.C. 1.14.99.29) in cells while differentially displaying their polysomal versus non-polysomal mRNA populations, we report the detection and classification of several mRNA species that indeed disappear from and reappear at polysomes in concert with inhibition and disinhibition, respectively, of hypusine formation. Based on initial sequence data, two translationally controlled enzymes, both critical for proliferation, are identified as candicate products of such mRNAs, methionine adenosyltransferase (E.C. 2.5.1.6) and cytochrome-c oxidase (EC 1.9.3.1) subunit I. The existence of such putative hypusine-dependent messenger nucleic acids (hymns) provides the basis for a proposal on their molecular function in onset of multiplication.
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PMID:Detection of a sub-set of polysomal mRNAs associated with modulation of hypusine formation at the G1-S boundary. Proposal of a role for eIF-5A in onset of DNA replication. 778 38

Damage to mitochondria as a result of the intrinsic generation of free radicals is theoretically involved in the processes of cellular aging. Herein, we investigated whether acutely administered melatonin, due to its free radical scavenging activity, would influence mitochondrial metabolism. Mitochondrial respiratory activity and respiratory chain complex I and IV activities in liver mitochondria from a strain of senescence-accelerated-prone mice (SAMP8) and a strain of senescence-accelerated-resistant mice (SAMR1) were measured when the animals were 12 months of age. Respiratory control index (RCI), ADP/O ratio, State 3 respiration and dinitrophenol (DNP)-dependent uncoupled respiration were significantly lower in SAMP8 than in SAMR1. In contrast, State 4 respiration was significantly higher in SAMP8 than in SAMR1. Activities of complexes I and IV in SAMP8 were significantly lower than in SAMR1. Melatonin administration (10mg/kg body weight, intraperitoneally) 1h prior to sacrifice significantly increased RCI, ADP/O ratio, State 3 respiration and DNP-induced uncoupled respiration in SAMP8 while also significantly reducing State 4 respiration in SAMP8. The injection of melatonin also significantly increased complex I activity in both mouse strains and complex IV activity in the liver of SAMP8 mice. These results document an age-related decrease in hepatic mitochondrial function in SAM which can be modified by an acute pharmacological injection of melatonin; the indole stimulated mitochondrial respiratory chain activity which would likely reduce deteriorative oxidative changes in mitochondria that normally occur in advanced age.
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PMID:Acutely administered melatonin restores hepatic mitochondrial physiology in old mice. 1253 Dec 50

Nitric oxide (NO) modulates the fluidity of a variety of membranes. Thus, the aim of the present work was to study if the inhibitory effect of NO on mitochondrial respiration is associated with its effects on membrane fluidity. Liver mitochondria and an inner mitochondrial membrane fraction (IMMF) were isolated from male Wistar rats by differential centrifugation. Oxygen consumption was measured polarographically and fluidity by the fluorescence polarization method. S-nitroso-N-acetylpenicillamine (SNAP) was used as a NO donor. It was observed that NO decreased IMMF fluidity and oxygen consumption in a concentration dependent fashion. However, SAM a fluidizing agent that prevented the decrement in fluidity produced by SNAP, failed to preserve oxygen consumption. Protection of sulfhydryl groups with dithiotreitol was utilized to evaluate the role of oxidation of these groups on IMMF respiration. Incubation with dithiotreitol did not preserve IMMF oxygen consumption. The data shown herein suggest that NO inhibits the respiratory chain by a mechanism not involving the modulation of membrane fluidity or the oxidation of sulfhydryl groups. Thus, it seems that the mechanism by which NO modulates mitochondrial respiration is by cytochrome oxidase inhibition, because (as reported by others) low concentrations of NO specifically inhibit reversibly cytochrome oxidase in competition with oxygen.
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PMID:Inhibition of mitochondrial respiration by nitric oxide is independent of membrane fluidity modulation or oxidation of sulfhydryl groups. 1616 23