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Query: UNIPROT:P06889 (Mol)
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A novel, simple, rapid, sensitive and reproducible microassay is described for determination of myoglobin and hemoglobin content of myocardial and skeletal muscle biopsy specimens from various mammals, birds and fish. As little as 50 mg of tissue is needed and myoglobin concentrations lower than 1 mg% can be detected. Myoglobin and hemoglobin are separated at alkaline pH by ammonium sulfate extraction followed by ultrafiltration. Heme content is determined by absorption of the Soret band when the hemoprotein extract is visibly colored or more sensitively by its peroxidase activity when the extract has low color. The heme reacts with tertiary-butyl hydroperoxide and orthotolidine to generate a blue color. Hemoglobin content is correlated with myoglobin content and is related to aerobic capacity and blood flow to the tissue. Myoglobin content varied over 5 orders of magnitude up to 7 per cent of the weight of tissue, whereas hemoglobin content varied over 2 orders of magnitude up to 6 per cent of tissue weight. Myoglobin content is increased in species with high basal metabolic rate, high physical activity, prolonged diving capacity, fatigue resistance, and red muscle, whereas it is decreased in white muscle, iron-deficient animals, animals with sedentary lifestyles, and in animals and tissues with small fiber diameters such as avian or fish hearts.
Mol Cell Biochem 1992 May 13
PMID:Rapid, simple and sensitive microassay for skeletal and cardiac muscle myoglobin and hemoglobin: use in various animals indicates functional role of myohemoproteins. 132 34

The heme vinyl substituents in a shark (Galeorhinus japonicus) myoglobin in its met-cyano form (MbCN) have been characterized by NMR and the results were compared with those of the well-studied sperm whale (Physter catodon) myoglobin. Their orientation has been inferred from NOE connectivities and the analysis of the hyperfine shifts based on the principal magnetic tensor determined by MATDUHM (Magnetic Anisotropy Tensor Orientation Determination Utilizing the Heme Methyls) [Yamamoto, Y., Nanai, N. and Chujo, R.(1990) J. Chem. Soc., Chem. Commun. 1556-1557]. It has been shown that the C3-vinyl group is oriented roughly orthogonal to the heme plane in both G. japonicus and P. catodon MbCNs at 35 degrees C and their C8-vinyl groups, on the other hand, are close to in-plane orientation. Although CO form of myoglobin (MbCO) and MbCN have been thought to be isostructural to each other, the C8-vinyl orientation for P. catodon MbCN is found to be different from the orthogonal orientation indicated in the crystal structure analysis of MbCO [Hanson, J.C. and Schoenborn, B.P. (1981) J. Mol. Biol. 153, 117-146]. Their mobility has been characterized quantitatively from the study of time-dependent NOE build-up between the selected pair of the vinyl proton resonances. It has been revealed that the heme C3- and C8-vinyl groups of approximately 1 mM G. japonicus MbCN at 45 degrees C undergo internal motion with the correlation time of 1.9 and 2.4 ns, respectively. Therefore, their oscillatory motion is faster by a factor of 4-5 compared with the protein overall tumbling. Difference in the internal mobility between the two vinyl groups in the active site of this Mb is attributed to their differential contact with the apo-protein.
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PMID:Orientation and mobility of the heme vinyl groups in myoglobins with the aid of NOE and MATDUHM NMR. 156 83

Heme is covalently attached to cytochrome c by the enzyme cytochrome c heme lyase. To test whether heme attachment is required for import of cytochrome c into mitochondria in vivo, antibodies to cytochrome c have been used to assay the distributions of apo- and holocytochromes c in the cytoplasm and mitochondria from various strains of the yeast Saccharomyces cerevisiae. Strains lacking heme lyase accumulate apocytochrome c in the cytoplasm. Similar cytoplasmic accumulation is observed for an altered apocytochrome c in which serine residues were substituted for the two cysteine residues that normally serve as sites of heme attachment, even in the presence of normal levels of heme lyase. However, detectable amounts of this altered apocytochrome c are also found inside mitochondria. The level of internalized altered apocytochrome c is decreased in a strain that completely lacks heme lyase and is greatly increased in a strain that overexpresses heme lyase. Antibodies recognizing heme lyase were used to demonstrate that the enzyme is found on the outer surface of the inner mitochondrial membrane and is not enriched at sites of contact between the inner and outer mitochondrial membranes. These results suggest that apocytochrome c is transported across the outer mitochondrial membrane by a freely reversible process, binds to heme lyase in the intermembrane space, and is then trapped inside mitochondria by an irreversible conversion to holocytochrome c accompanied by folding to the native conformation. Altered apocytochrome c lacking the ability to have heme covalently attached accumulates in mitochondria only to the extent that it remains bound to heme lyase.
Mol Cell Biol 1991 Nov
PMID:Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. 165 31

Heme-deficient mutants of Rhizobium and Bradyrhizobium have been found to exhibit diverse phenotypes with respect to symbiotic interactions with plant hosts. We observed that R. meliloti hemA mutants elicit nodules that do not contain intracellular bacteria; the nodules contain either no infection threads ("empty" nodule phenotype) or aberrant infection threads that failed to release bacteria (Bar- phenotype). These mutant nodules expressed nodulin genes associated with nodules arrested at an early stage of development, including ENOD2, Nms-30, and four previously undescribed nodulin genes. These nodules also failed to express any of six late nodulin genes tested by hybridization, including leghemoglobin, and twelve tested by in vitro translation product analysis which are not yet correlated with specific cloned genes. We observed that R. meliloti leucine and adenosine auxotrophs induced invaded Fix- nodules that expressed late nodulin genes, suggesting that it is not auxotrophy per se that causes the hemA mutants to elicit Bar- or empty nodules. Because R. meliloti hemA mutants elicit nodules that do not contain intracellular bacteria, it is not possible to decide whether or not the Fix- phenotype of these nodules is a direct consequence of the failure of R. meliloti to supply the heme moiety of hololeghemoglobin. Our results demonstrate the importance of establishing the stage in development at which a mutant nodule is arrested before conclusions are drawn about the role of small metabolite exchange in the symbiosis.
Mol Gen Genet 1991 Dec
PMID:Nodules elicited by Rhizobium meliloti heme mutants are arrested at an early stage of development. 176 39

All nucleated animal cells synthesize heme to provide the prosthetic group of respiratory cytochromes. Large amounts of heme are synthesized by erythroid cells for hemoglobin production and by liver cells for drug-induced cytochromes P450. This review focuses on the first enzyme of the heme biosynthetic pathway, 5-aminolevulinate synthase (ALAS), which catalyzes the rate-controlling step in liver and possibly other tissues. We report that there are two distinct human genes for ALAS: one, a housekeeping gene, is probably ubiquitously expressed while the other is active only in erythroid tissue. By contrast it has been reported that, for porphobilinogen deaminase, the third enzyme of the heme pathway, there is a single human gene with two promoters; one functional in all tissues, the other erythroid specific. In liver, transcription of the housekeeping ALAS gene is induced by drugs and repressed by heme. Heme also acts in a novel way to prevent transport of ALAS into mitochondria, its site of function. Porphyrias result from inherited defects in enzymes of the heme pathway subsequent to ALAS and the molecular abnormality is now known for the most common subtype of acute intermittent porphyria. In developing red cells, levels of ALAS are regulated by increased gene transcription and by a post-transcriptional mechanism, in which iron most probably controls translation of erythroid ALAS mRNA through an iron-responsive element identified in the 5' untranslated region of the mRNA. The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias.
Mol Biol Med 1990 Oct
PMID:Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. 209 58

The Vitreoscilla hemoglobin protein has been implicated in earlier studies to serve a globin-like function under oxygen-limited growth conditions. Evidence is presented using fractionation as well as proteinase K accessibility techniques to prove that a considerable amount of this protein is localized in the periplasmic space of the cell. Genetic evidence points towards the existence of information within the N-terminal domain of the protein that plays a role in the process of protein export. However, this sequence is not cleaved in the process of translocation. Analysis of the primary structure of this region reveals several unusual features. Instead of positively charged residues at its amino terminus, it has a negative charge. The overall hydrophobicity of the central region of this sequence is significantly lower than in typical leader peptides due to the presence of a charged residue. In keeping with the likelihood that such an export signal may not be very efficient, a substantial fraction of the total cellular hemoglobin can also be detected in the cytoplasm. Heme is incorporated in both cytoplasmic and periplasmic globin as indicated by the ability of protein from both fractions to bind carbon monoxide. The secretion of this protein into the periplasm raises questions concerning the physiological significance of its localization. Dimensional analysis of a model based on the facilitated diffusion hypothesis, which was initially proposed to account for the effects of eukaryotic globins on oxygen transport, suggests that periplasmic globin can support an additional oxygen flux to the respiratory apparatus that may be physiologically significant.
J Mol Biol 1989 Nov 05
PMID:Evidence for partial export of Vitreoscilla hemoglobin into the periplasmic space in Escherichia coli. Implications for protein function. 268 32

In Saccharomyces cerevisiae, the COX5a and COX5b genes encode two forms of cytochrome c oxidase subunit V, Va and Vb. We report here that heme increases COX5a expression and decreases COX5b expression and that the HAP2 and REO1 genes are involved in positive regulation of COX5a and negative regulation of COX5b, respectively. Heme regulation of COX5a and COX5b may dictate which subunit V isoform is available for assembly into cytochrome c oxidase under conditions of high- and low-oxygen tension.
Mol Cell Biol 1988 Oct
PMID:Differential regulation of the two genes encoding Saccharomyces cerevisiae cytochrome c oxidase subunit V by heme and the HAP2 and REO1 genes. 284 35

A hemoprotein present in minute quantities in Leishmania donovani promastigotes was isolated, purified and spectrally characterized as cytochrome c555. Physicochemical characterization revealed electrophoretic mobility of 1.6 X 10(-5) cm2 V-1 s-1, an isoelectric point (pI) of 9.9, a relative molecular weight (Mr) of 11.9 kDa and half-wave potential (Ep) of -1.058 V. Values obtained were compared with those of horse heart cytochrome c subjected to the same analyses. Heme c555 was also prepared and spectrally characterized. The results indicated that leishmanial cytochrome c555 is similar but not identical to its crithidial counterpart.
Mol Biochem Parasitol 1986 Oct
PMID:Purification and properties of cytochrome c555 from Leishmania donovani. 302 42

In Saccharomyces cerevisiae the anaerobic (oxygen-repressed) ANB1 gene and a group of aerobic (oxygen-induced) genes are coordinately regulated by the ROX1 gene. We report here that heme, known as an inducer of aerobic genes, also causes inhibition of ANB1 expression. Thus, in combination with the ROX1 gene product heme has an opposite effect on the expression of anaerobic and aerobic genes. Accumulation of ANB1 mRNA was sharply decreased in anaerobic cells grown in the presence of heme. This effect must operate at the level of transcription since heme also inhibited accumulation of CYC1 mRNA from an ANB1-CYC1 fusion. Heme precursors did not appear to function either as inhibitors or as activators. Oxygen itself also had no effect on transcription of ANB1. Repression by heme cannot be attributed to the respiratory competence conferred by heme since both ANB1 and the aerobic genes tr-1 and CYC1 were regulated normally in [rho 0] mutants. The results are consistent with a classical allosteric coeffector function for heme, although more indirect explanations are tenable. A role for the ROX1 gene product in transcriptional regulation can be inferred from the observation that there was no inhibition of ANB1 expression by heme in rox1 mutants. Judging from this epistasis the rox1 phenotype is not due to a defect in heme production; this would indicate that the ROX1 factor functions by mediating the effect of heme on transcription.
Mol Cell Biol 1986 Dec
PMID:Negative regulation of the Saccharomyces cerevisiae ANB1 gene by heme, as mediated by the ROX1 gene product. 354 Jun 7

The regulation of cardiac heme oxygenase and cytochrome P-450 mixed function oxidase was studied in the rabbit heart. Heme oxygenase activity is found in ventricular and atrial microsomal fractions. This activity is NADPH dependent, and is inhibited by tin and zinc protoporphyrin, but not by either SKF 525A or 7,8-benzoflavone. Immunologic studies of cardiac heme oxygenase demonstrate that antibodies prepared against human purified hepatic heme oxygenase recognize rabbit atrial heme oxygenase and inhibit the enzyme activity by 92%. In contrast, control immunoglobulin does not inhibit heme oxygenase activity. Further, the western blotting technique demonstrates that a similar band of protein with a molecular weight of 32,000 exists in cardiac microsomes and that no protein cross-reacts with purified hepatocyte heme oxygenase. Marked induction of atrial heme oxygenase is observed in microsomal fractions prepared from rabbits treated with cobalt chloride. Atrial microsomes possess 0.24 nmol of cytochrome P-450 as compared to 0.68 nmol/mg protein in microsomes from the liver. The levels of aryl hydrocarbon hydroxylase (AHH) activity, a cytochrome P-450-dependent enzyme, in ventricle and atrium are stimulated by a NADPH-generating system and are sensitive to 7,8-benzoflavone, and SKF 525A, known inhibitors of cytochrome P-450 mixed function oxidase. AHH activity in ventricular and atrial microsomes is 2-3% of that seen in liver microsomes whereas the P-450 content/mg protein is about 20% of that observed in the liver. AHH activity is mediated by a form of cytochrome P-450 that is inducible by 3-methylcholanthrene/beta-naphthoflavone. A possible new role of the heart cytochrome P-450 system in cardiac function is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Jan
PMID:Identification of heme oxygenase and cytochrome P-450 in the rabbit heart. 355 Jan 6


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