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)

The induction of 5'-aminolevulinate synthase (ALV synthase) activity in adult muscle by overload occurs in the absence of proportional changes in its mRNA content. Complete interpretation of these findings is difficult because little is known of the basal regulation of ALV synthase expression in muscle. In three adult chicken muscle fiber types (n = 5 each), differences in ALV synthase activity were correlated (r greater than or equal to 0.89; P less than 0.05) to the activities of cytochrome oxidase (COX) and citrate synthase (CS) and to levels of the "liver" isoform of ALV synthase mRNA. During posthatch development, ALV synthase activity and mRNA levels (n = 3-6 per time point) also covaried with changes in COX and CS activity. The highest levels of ALV synthase mRNA in muscle are observed early in myogenesis prior to induction of COX activity. The regulation of ALV synthase is also tissue-specific because the higher basal levels of ALV synthase activity in liver mitochondria are associated with disproportionately less oxidative enzyme activity and less of the liver ALV synthase isoform mRNA than in muscle.
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PMID:Muscle-specific regulation of the heme biosynthetic enzyme 5'-aminolevulinate synthase. 192 29

1. Basal levels and allyl-isopropylacetamide (AIA) or veronal induced levels of delta-aminolevulinate synthetase (ALA-S), cytochrome P-450 (cyt P-450) and cytochrome oxidase were determined in tumor (T) and liver of both normal mice (NM) and T bearing mice (TBM). 2. Basal levels of ALA-S were nearly the same in either source. The amount of cyt P-450 was lower in TBM liver than in NM liver, and no detectable in T. While the basal activity of cytochrome oxidase in TBM liver and T were higher than those of NM liver. 3. In AIA intoxicated animals there was a lower induction of ALA-S in liver of TBM than in NM liver. There was no induction in T ALA-S. The loss of cyt P-450 was less in TBM liver when compared with NM liver. 4. The induction level of cyt P-450 after veronal administration was nearly the same in liver of both TBM and NM. 5. We conclude that lower induction of liver ALA-S activity in TBM liver is due to correspondingly lower drug metabolism ability of TBM liver. Otherwise our results suggest that the control mechanism operating in T and probably in its original tissue are different from those described for normal liver.
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PMID:Heme regulation in mouse mammary carcinoma and liver of tumor bearing mice--I. Effect of allyl-isopropylacetamide and veronal on delta-aminolevulinate synthetase, cytochrome P-450 and cytochrome oxidase. 217 97

The regulation of the mitochondrial enzyme 5'-aminolevulinate synthase (ALV synthase) activity during chronic weight-bearing activity (overload) in chicken skeletal muscle was investigated. Maximal enzyme activity was increased 2.5- and 4.0-fold after 3 and 7 days of overload. The content of ALV synthase mRNA (ng/mg total RNA) was not changed after 3 days but increased (20%; P less than 0.05) after 7 days of overload. Normalizing the content of ALV synthase mRNA relative to the increase in total RNA indicated that ALV synthase mRNA increased by 1.6- and 2.0-fold at 3 and 7 days, respectively. On this basis, the increase in enzyme activity per gram protein exceeded the increase in mRNA content per gram protein by 60-70%. During overload, the activity of cytochrome oxidase was unchanged after 3 days but increased by 1.5-fold (P less than 0.05) after 7 days of overload. The data indicate that 1) the initial rise in ALV synthase mRNA and activity due to overload occurs in the absence of a prior change in the level of cytochrome oxidase, an enzyme that requires heme for its assembly, and 2) induction of ALV synthase activity is regulated largely by processes at the translational or posttranslational steps.
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PMID:Regulation of 5'-aminolevulinate synthase activity in overloaded skeletal muscle. 238 4

Activities of mitochondrial enzymes in blood cells from 69 patients with primary sideroblastic anemia were determined to elucidate the pathogenesis of the disease. In erythroblasts of patients with primary acquired type the activities of both delta-aminolevulinic acid synthetase and mitochondrial serine protease were inevitably decreased. The susceptibility to the protease of apo-delta-aminolevulinic acid synthetase prepared from erythroblasts of patients with this type was within the normal range, in contrast to that of pyridoxine-responsive anemia. The activities of mitochondrial enzymes such as cytochrome oxidase, serine protease, and oligomycin-sensitive ATPase, except citrate synthetase, were usually decreased in mature granulocytes of the patients. Patients with hereditary sideroblastic anemia also had decreased delta-aminolevulinic acid synthetase activity in erythroblasts, and decreased serine protease activity in both erythroblasts and mature granulocytes. Mature granulocytes obtained from patients with pyridoxine-responsive anemia before therapy had decreased cytochrome oxidase activity, however, the activity increased to a normal level when the patients were in remission. The activities of other mitochondrial enzymes in mature granulocytes were within normal range in these patients before pyridoxine therapy. The activities of these mitochondrial enzymes in lymphocytes were within normal range in all groups of patients with primary sideroblastic anemia. We suggest that patients with primary acquired, and possibly also those with hereditary sideroblastic anemia have impaired mitochondrial function in both erythroblasts and granulocytes. That only anemia is observed in these patients is because a functional abnormality of mitochondria in erythroblasts is most important because of the role of mitochondria in the formation of heme in erythrocyte development. In contrast to these two types of sideroblastic anemia, only delta-aminolevulinic acid synthetase in both erythroblasts and granulocytes seems to be impaired in patients with pyridoxine-responsive anemia.
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PMID:Multiple enzymatic defects in mitochondria in hematological cells of patients with primary sideroblastic anemia. 624 45

The basal- and allylisopropylacetamide-induced activities of the first enzyme of heme biosynthesis, delta-aminolevulinic acid synthase (ALAS) were measured in hepatic mitochondria and cytosol of young, adult, and aged Fisher 344 rats. The total cellular ALAS activity induced by allylisopropylacetamide decreased 67% with age. The specific activity of mitochondrial ALAS in normal and induced animals decreased with aging when assayed in whole or broken mitochondria. The levels of ALAS which accumulated in the cytosol after allylisopropylacetamide administration were proportionally greater in both the young and senescent than in the mature animals. During aging, no evidence for a fragile population of mitochondria in either normal or induced animals was observed suggesting that mitochondrial matrix proteins are not released during homogenization. The hepatic mitochondrial content decreased during aging when calculated using both a membrane-bound marker enzyme cytochrome oxidase and a matrix marker enzyme citrate synthase and was unaffected by allylisopropylacetamide treatment. This reduced mitochondrial content further diminishes the level of functional ALAS available in the liver during senescence. This study confirms the age-dependent decrease in mitochondria ALAS in normal and induced animals and also suggests an age-related change in the process by which cytosolic ALAS is translocated into the mitochondria.
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PMID:Aging-related decreases in hepatic mitochondrial and cytosolic delta-aminolevulinic acid synthase during experimental porphyria. 683 17

Endurance training leads to an increase in the content of individual mitochondrial hemeproteins in skeletal muscle. To deduce the control mechanisms involved, cytochrome oxidase (COX) activity was compared with 1) the content of COX subunits III and IV and 2) 5-aminolevulinate synthase (ALAS) activity and mRNA content. In the plantaris muscle of female rats run daily for up to 28 days, ALAS activity was elevated 100% (P < 0.01) after 3 days and remained 150 and 125% higher (P < 0.001) after 7 and 28 days of running, respectively, than control. COX activity was also increased, but not until day 7 (40%; P < 0.05), and reached a maximal value 80% higher than control (P < 0.001) in the 28-day group. Compared with control, the content of COX subunit III and IV and ALAS mRNAs was not significantly changed by the training. The increased activities of COX and ALAS appear to be regulated by translational or posttranslational steps in the protein expression pathway. The induction of ALAS before COX suggests that the increased activity of COX may require increased synthesis of heme.
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PMID:Cytochrome oxidase in muscle of endurance-trained rats: subunit mRNA contents and heme synthesis. 838 7

Exercise results in rapid increases in expression of the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and in mitochondrial biogenesis in skeletal muscle. PGC-1alpha regulates and coordinates mitochondrial biogenesis, and overexpression of PGC-1alpha in muscle cells results in increases in mitochondrial content. In this context, it has been proposed that the increase in PGC-1alpha protein expression mediates the exercise-induced increase in mitochondrial biogenesis. However, we found that mitochondrial proteins with a short half-life increase as rapidly as, or more rapidly than, PGC-1alpha protein. This finding led us to hypothesize that activation, rather than increased expression, of PGC-1alpha mediates the initial phase of the exercise-induced increase in mitochondria. In this study, we found that most of the PGC-1alpha in resting skeletal muscle is in the cytosol. Exercise resulted in activation of p38 MAPK and movement of PGC-1alpha into the nucleus. In support of our hypothesis, binding of the transcription factor nuclear respiratory factor 1 (NRF-1) to the cytochrome c promoter and NRF-2 to the cytochrome oxidase subunit 4 promoter increased in response to exercise prior to an increase in PGC-1alpha protein. Furthermore, exercise-induced increases in the mRNAs of cytochrome c, delta-aminolevulinate synthase, and citrate synthase also occurred before an increase in PGC-1 protein. Thus, it appears that activation of PGC-1alpha may mediate the initial phase of the exercise-induced adaptive increase in muscle mitochondria, whereas the subsequent increase in PGC-1alpha protein sustains and enhances the increase in mitochondrial biogenesis.
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PMID:Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. 1709 48

The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed a single treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1alpha KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained approximately 37 h after the last training session. Resting muscles of the PGC-1alpha KO mice had lower ( approximately 20%) cytochrome c (cyt c), cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK) alpha1, AMPKalpha2, and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-beta and the level of HKII mRNA similarly in WG of KO and WT. In contrast, cyt c mRNA in soleus was upregulated in WT muscles only. Exercise training increased cyt c, COXI, ALAS1, and HKII mRNA and protein levels equally in WT and KO animals, but cyt c, COXI, and ALAS1 expression remained approximately 20% lower in KO animals. In conclusion, lack of PGC-1alpha reduced resting expression of cyt c, COXI, and ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1alpha is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1alpha can exert these adaptations.
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PMID:PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. 1807 19

The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p<0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p<0.005, p<0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p<0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p<0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p<0.05, p<0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p<0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p<0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p<0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption.
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PMID:The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities. 1838 29

The effect of low-level irradiation of tumor-bearing rats on the structural and functional organization of the cytochrome part of respiratory chain of mitochondria isolated from Guerin's carcinoma has been investigated. The maximal reduction in the mitochondrial cytochromes a, b and c content was observed at the terminal stage of Guerin's carcinoma. A low-level irradiation during initial stages of oncogenesis produced opposite changes in the mitochondrial cytochrome content. The possible mechanism of mitochondrial haem-containing cytochromes content reduction may be attributed to impairment in their formation caused by inhibition of the key enzyme of haem synthesis, 5-aminolevulinate synthase. The determined changes of the mitochondrial cytochromes quantitative content were accompanied by decreased activity of cytochrome oxidase. The preliminary low-level irradiation of the tumor-bearing animals produced further reduction in the cytochrome oxidase activity observed in all experimental periods.
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PMID:[The change in the structural and functional organization of the Guerin's carcinoma cytochrome part of respiratory chain in tumor carriers in the conditions of preliminary low-level irradiation]. 2335 Feb


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