Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymatic destruction of oxidizing products produced during metabolic reduction of oxygen in the cell (such as singlet oxygen, H2O2 and OH radical) involves the concerted action of superoxide dismutase-which removes O-2 and yields H2O2-and H2O2 removing enzymes such as catalase and glutathione peroxidase. A difference in distribution or ratio of these enzymes in various tissues may result in a different reactivity of oxygen radicals. It was found that in red blood cells superoxide dismutase and catalase are extracted in the same fraction as hemoglobin, while glutathione peroxidase appears to be "loosely" bound to the cellular structure. This suggests that in red blood cells catalase acts in series with superoxide dismutase against bursts of oxygen radicals formed from oxyhemoglobin, while glutathione & peroxidase may protect the cell membrane against low concentrations of H2O2. On the other hand, catalase activity is absent in various types of ascites tumor cells, while glutathione peroxidase and superoxide dismutase are found in the cytoplasm. However, the peroxidase/dismutase ratio is lower than in liver cells, and this may provide an explanation for the higher susceptibility of tumor cells to treatments likely to involve oxygen radicals.
Mol Cell Biochem 1976 Jan 31
PMID:Enzyme defense against reactive oxygen derivatives. II. Erythrocytes and tumor cells. 81 6

Hemoglobin M Milwaukee (beta67E11 Val leads to Glu) is a naturally occurring valency hybrid containing two permanently oxidized hemes on the beta chains. In this mutant, the two abnormal beta chains cannot combine with ligands whereas the two alpha chains are normal and can combine with oxygen with a Hill coefficient varying from 1.1 to 1.3 [Udem et al. (1970), J Mol. Biol. 48, 489]. High-resolution proton nuclear magnetic resonance spectroscopy at 250 MHz has been used to investigate the exchangeable, ring-current shifted, ferrous and ferric hyperfine shifted resonances of Hb M Milwaukee in the absence and presence of organic phosphates. The alpha-heme environment, as manifested by the ring-current shifted resonances in the liganded form as well as the ferrous hyperfine shifted resonances in unliganded form, and subunit interactions, as manifested by the exchangeable resonances, are similar in Hb M Milwaukee to those in normal adult human hemoglobin. Organic phosphates can partially or completely inhibit the structural transformation which normally accompanies the binding of oxygen or carbon monoxide to Hb M Milwaukee. Upon stepwise addition of oxygen to deoxy Hb M Milwaukee, the hyperfine shifted resonance spectra of ferric beta chains show features which cannot be attributed to either fully deoxy or oxy species. However, the spectra for partially oxygenated Hb M Milwaukee can be described as an appropriately weighted average of the spectra of sero, singly, and doubly oxygenated species. The ferric hyperfine shifted resonance spectrum of the singly oxygenated intermediate has been calculated by a method employing least-squares analysis of the spectra of partially oxygenated Hb M Milwaukee at several values of oxygen saturation. The spectrum of this intermediate exhibits features which cannot be accounted for by a two-structure model. The present results are consistent with a sequential model for the oxygenation of this mutant hemoglobin. In view of the similarities between normal adult hemoglobin and Hb M Milwaukee, it is suggested that a two-state concerted allosteric model does not provide an adequate description of the structure-function relationship in normal adult hemoglobin.
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PMID:Proton nuclear magnetic resonance studies of hemoglobin M Milwaukee and their implications concerning the mechanism of cooperative oxygenation of hemoglobin. 84 26

One-half of the twenty amino acids of the genetic code are just one mutational step away from the chain-terminator codons UAA, UAG, and UGA. It is postulated that somatic mutation to terminator is a hazard to which the organism has and to respond by adjusting certain proteins in the direction of fewer mutable residues. This view is supported by calculations based on the primary structure of five of the human hemoglobin chains. Each chain is scored for mutability to terminator in accord with the numbers and kinds of amino acids present. Among the adult chains, the most essential one, the alpha, has lowest mutability. The beta and delta follow, and in order of the presumed harm to the organism of a shortage of chain copies. Ante-natal chains tend to have higher mutabilities, supporting the view that cumulative mutational change in DNA can do little if the gene ceases to transcribe early in life. Two other predicitons based on the supposition of effective selection against mutability to terminator are also met: chain length of polypeptides is negatively correlated with their scores for mutability to terminator, and examination of the recently determined sequence of beta messenger RNA shows preferential use of codons that are not readily mutable to terminator.
J Mol Evol 1977 May 13
PMID:Hemoglobin and the genetic code. Evolution of protection against somatic mutation. 86 25

The manual sequencing of the tryptic peptic from the alpha and beta chains of dog hemoglobin is described, including evidence for the existence of two alphaT-13 peptides and thus 2 alpha chains, one with threonine and one with alanine at position 130. Although the actual sequence was published in 1970, the evidence on which it was based has not previously appeared.
J Mol Evol 1977 May 13
PMID:The amino acid sequence of dog (Canis familiaris) hemoglobin. 86 26

The amino acid compositions of the tryptic peptides of the following carnivore hemoglobin chains have been determined: gray fox (Urocyon cineroargenteus); raccoon (Procyon lotor); polar bear (Thalarctos maritimus); coati mundi (Nasua nasua) beta chain; coati mundi (Nasua narica) two beta chains; cat (Felis catus) alpha chain; and lion (Pantbera leo) beta chain. These provide a basis for future sequencing of these hemoglobins and construction of an evolutionary tree. The specific results are summarized in the following article (Stenzel and Brimhall, 1977).
J Mol Evol 1977 May 13
PMID:On the tryptic peptides from hemoglobin chains of six carnivores. 86 27

Linoleic acid hydroperoxydes (LOOH) containing 13-hydroperoxyoctadeca-9,11-(75%) and 9-hydroperoxyoctadeca-10,12-dienoic acid (25%) were emulsified at pH 6.5. After addition of hemoglobin, ferrous ions, ferric ions, cysteine or ascorbic acid the emulsions were stored 19 hours at 22 degrees C. The decrease in the diene and peroxyde concentrations and the formation of volatile carbonyl compounds were analysed. Ferrous ions and ascorbic acid were the strongest producers of volatile carbonyl compounds. In the presence of 10(-3) Mol ascorbic acid 6 mumol volatile aldehydes arise from 75 mumol LOOH. Hexanal (70 mol-%) was the main component of the aldehyde fraction. For plant foodstuffs the significance of the reaction of fatty acids hydroperoxydes with ascorbic acid for the formation of flavour substances is discussed.
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PMID:[Breakdown of linoeic acid hydroperoxydes. Formation of volatile carbonyl compounds (author's transl)]. 97 38

NMR spectra of the downfield region of normal adult hemoglobin are reported as a function of oxygenation and temperature. Spectra were run in D2O at pD 7.4. A specially made NMR tube insert allowed precise measurement of the degree of oxygenation and of methemoglobin formation before and after taking the NMR spectrum. Plots of the estimated intensity of the most downfield prominent NMR peak, identified as arising from a deoxy-beta subunit by Davis et al. ((1971) J. Mol. Biol. 60, 101-111), versus the average degree of oxygenation y, measured optically, yield a nearly straight line within experimental error, for samples stripped of organic phosphates and for samples containing 2,3-diphosphoglycerate or inositol hexaphosphate. Intensities of peaks further upfield than this peak, previously attributed to deoxy-alpha subunits, are difficult to measure directly especially for samples containing inositol hexaphosphate. The latter samples show broadening in these alpha peaks as the degree of oxygenation increases. This extra broadening appears to increase with temperature. Linearity of the beta peak intensity with oxygenation is expected if there is no large oxygen affinity difference between alpha and beta subunits. However, the cooperativity of binding, and inaccuracy of the data, make it impossible to make accurate estimates of affinity differences.
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PMID:NMR study of relative oxygen binding to the alpha and beta subunits of human adult hemoglobin. 99 7

The subunit dissociation of human hemoglobin A by the aliphatic acid salts at neutral pH has been investigated by light-scattering molecular-weight measurements at 630 nm. Dissociation of hemoglobin tetramers to alphabeta dimers is observed in essentially all experiments at low to intermediate levels of salt concentrations, below the denaturation transitions, described in the accompanying paper (Ibanez, V.S., and Herskovits, T.T. (1976), Biochemistry 15, preceding paper in this issue). The effectiveness of the salts as subunit dissociating agent, reflected by the slopes, s, of the plots of deltaGDdegrees, the standard free energy of dissociation, vs. [D], the salt concentration, is found to increase with increasing alkyl chain length or hydrocarbon content of the salt. Estimates of the apparent number of amino acid sites at the areas of contact per alphabeta dimer formed, N', based on the slopes of the higher members of the series have been obtained using the equation, deltaGDdegrees = deltaGD,Wdegrees - 2N'RTKB[D]. Independent estimates of the binding constant, KB, required for these calculations were based on free-energy transfer data of hydrophobic amino acid alkyl groups and protein denaturation data. Our estimates of N' denaturation data. Our estimates of N' obtained with the more reliable data of the higher members of salt series are in the ranges of 19 and 27 amino acid groups, shown by the x-ray crystallographic structure of horse and human hemoglobin of Perutz (Perutz, M.F., et al. (1968), Nature (London) 219, 131) and Fermi ((1975) J. Mol. Biol. 97, 237) for the smaller alpha1 beta2 contact areas in the tetrameric structure. The lower estimates than 27 based on our dissociation of human hemoglobin suggest that several of the amino acid residues in the contact areas of the subunits are partially exposed to solvent. The increasing effectiveness of the higher mn imporant source of stabilization of the tetrameric structure of hemoglobin.
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PMID:Light-scattering investigations of the subunit dissociation of human hemoglobin A. Effects of the aliphatic acid salts. 100 84

Comparative studies of red cells 2, 3 Diphosphoglycerate (DPG) and its effect on hemoglobin oxygen affinity from a taxonomically diverse set of mammals indicate two anomalous groups: members of the superfamilies Bovoidea (Actiodactyla) and Feloidea (Carnivora). In both taxa all of the individuals assayed had very low or unmeasurable quantities of DPG and red cell lysates with little, if any, DPG effect as measured by the change in oxygen affinity in the absence and presence of the phosphate. However, in both groups compensatory changes have occurred in hemoglobin structure and function so as to reduce the native oxygen affinity and thus cause them to resemble the hemoglobins of DPG-utilizing mammals as they occur in the setting of the red cell. We conclude that this parallelism of function is the result of convergent evolution.
J Mol Evol 1976 Dec 30
PMID:Functional aspects of hemoglobin evolution in the mammals. 101 Dec 62

The investigation of 163 spontaneous point mutations of the human hemoglobin and the analysis of the genetic code make it possible to estimate the relative probability of transversions, which happens to be 0.30. From 23 possible nonsense mutations 15 are the transversions. Hence the genetic code provides the low probability of the mutational termination of the protein chain. The most dangerous are the mutations in the codon UGG (Trp).
Mol Biol (Mosk)
PMID:[Transversions and transitions]. 105 35


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