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)

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

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

Hemoglobin Vancouver is a new abnormal hemoglobin with an amino acid substitution of the normal aspartyl residue 73 of the beta chain by a tyrosyl residue. It was discovered in a man of Chinese descent in association with beta thalassemia. It was subsequently detected in a sister in association with normal Hb A. The oxygen affinity of the abnormal hemoglobin is decreased but its subunit interaction is normal. The Bohr effect may be slightly increased. This is the fourth abnormal hemoglobin to be found with a substitution at beta73. The others are Hb C-Harlem (alpha2beta2 6Glu replaced by Val and 73 Asp replaced by Asn), Hb Korle-Bu (alpha2beta2 73Asp replaced by Asn), and Hb Mobile (alpha2beta2 73Asp replaced by Val). Although Hb Mobile was found in the present studies to have a decreased affinity for oxygen, Hbs C-Harlem and Korle-Bu have been reported to be normal. These observations of functional differences for variants of beta73 added to earlier observations of the role of the normal beta73 residue to the aggregation of sickle deoxyhemoglobin indicate that this position of the molecule may be important in intra as well as intermolecular interactions.
J Mol Evol 1976 Dec 31
PMID:Hemoglobin Vancouver [alpha2beta2(73)(E17) Asp replaced by Tyr]: its structure and function. 101 30

1. Twelve patients with symptomatic Paget's disease were studied before starting treatment with salmon calcitonin (12-5 mug) subcutaneously twice daily. Eleven of them were studied again after 3 months on this therapy. 2. Although pretreatment values for urinary total hydroxyproline excretion and cardiac output were considerably increased in some patients, there was no correlation between these two variables in the group as a whole. 3. Treatment resulted in a striking reduction in disease activity; the mean urinary hydroxyproline decreased 67%. 4. There was, however, no significant fall in cardiac output or change in oxygen transport during treatment. 5. Of the eight patients with bone pain who received treatment, five claimed complete pain relief.
Clin Sci Mol Med Suppl 1975 Jun
PMID:Effect of salmon calcitonin on cardiac output, oxygen transport and bone turnover in patients with Paget's disease. 105 85

Two hypotheses have been presented to explain the grossly biphasic oxygen release kinetics observed when hemoglobins are studied with the oxygen pulse technique [Gibson (1973) Proc. Nat. Acad. Sci. USA 70, 1-4]. Hypothesis I suggests that the two phases result from cooperativity, with the fast phase being oxygen release from the low affinity (T) state and the slow phase being oxygen release from molecules that have switched to the high affinity (R) state. Hypothesis II suggests that the biphasic curves are due to a large (factor of 20-30) difference in oxygen release from the two types of subunits within deoxyhemoglobin. In order to experimentally discriminate between these two hypotheses, we reinvestigated the oxygen pulse reaction for hemoglobin Kansas (alpha2 beta2 102 Asn leads to Thr) in the absence and presence of inositol hexaphosphate, since recent high resolution nuclear magnetic resonance studies have shown that this allosteric cofactor stabilizes hemoglobin Kansas in T even when fully liganded [Ogawa, Mayer, and Shulman (1972) Biochem. Biophys. Res. Commun. 49, 1485-1491]. The results of these studies clearly favor hypothesis I over hypothesis II as being the correct interpretation for the oxygen pulse results. However, we have found evidence that suggests that oxygen release and binding in T are surprisingly faster than previously observed. Furthermore, within T, there is some spectral and kinetic heterogeneity for oxygen release from adult hemoglobin and hemoglobin Kansas. The magnitude of this kinetic heterogeneity in T appears to be about the same as that seen in the high affinity, R, state. The exchange of hypothesis II for hypothesis I more strongly favors views of cooperative oxygen binding involving both types of subunits, as required if the allosteric model of Monod, Wyman, and Changeux [(1965) J. Mol. Biol. 12, 88-118] is considered operative.
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PMID:Magnitude of subunit inequivalence for oxygen release from hemoglobin: reinvestigation of the oxygen-pulse experiment. 106 81

1. An exercise test has been developed which is suitable for elderly or frail subjects. It is based on free walking at three different speeds on a level indoor course of 256m. The subject sets his own pace in accord with simple instructions. 2. Twenty-four elderly men and ten young men took part in the study. 3. The time and number of paces taken to cover two sections of 100m within the course were used to establish that the subjects walked steadily. Walking speed, pace frequency and stride length were then calculated. 4. Heart rate was obtained with body-borne tape recorders and related to the walking speed. The heart rate at a standard walking speed could then be obtained by interpolation. This is an assessment of the cardiovascular response to exercise (physical condition). The variation on repeating the test was +/-5 per cent and there was no significant difference between the two age groups. 5. The assessment was found to correlate moderately well with a conventional assessment of physical condition based on oxygen uptake from tests on a bicycle ergometer. 6. The test could also be used as a performance index since walking speed was characteristic for the subject. The younger group walked significantly faster than the older group. As a performance index the test is therefor sensitive to age differences.
Clin Sci Mol Med 1976 Dec
PMID:Self-paced walking as a method for exercise testing in elderly and young men. 107 Apr 26

The activities of isocitrate dehydrogenase (NAD), isocitrate dehydrogenase (NADP) and oxoglutarate dehydrogenase have been investigated in Saccharomyces cerevisiae grown in a variety of aerobic and hypoxic conditions, the latter including oxygen deprivation, high glucose concentration, addition of inhibitors of mitochondrial protein synthesis, respiratory inhibition by azide, and impaired respiration mutants. All hypoxic conditions led to a marked decrease of oxoglutarate dehydrogenase and significant decreases of the two isocitrate dehydrogenases. According to its kinetic properties, the NAD-isocitrate dehydrogenase will not be operative in hypoxia "in vivo". From these and other related facts it is concluded that hypoxic conditions in yeast generally lead to a splitting of the tricarboxylic acid cycle and that glutamate synthesis in these conditions takes place through the coupling of the NADP-linked isocitrate and glutamate dehydrogenases.
Mol Cell Biochem 1975 Feb 28
PMID:Isocitrate dehydrogenases and oxoglutarate dehydrogenase activities of baker's yeast grown in a variety of hypoxic conditions. 109 51

1. The cardiogenic oscillations in the concentration of nitrogen and argon in expired gas, which are seen after the inspiration from residual volume of pure oxygen or a bolus of argon, have been studied in normal subjects and in patients with atrial fibrillation. 2. In the upright position of the subject, the peaks of nitrogen and argon concentration coincide with ventricular systole, although there is a transit delay along the tracheobronchial tree before any change of concentration occurs at the mouth. 3. Studies in different postures demonstrated that the effect of the heart is predominantly due to a reduction in cardiac volume during systole with a decrease in airflow from regions adjacent to the heart. These areas contain a different concentration of nitrogen and argon in the alveolar air from the more apical regions. 4. It has been shown that the results are consistent with the present concepts of the influence of gravity on the distribution of inspired air.
Clin Sci Mol Med 1975 Jan
PMID:Cardiogenic oscillations of nitrogen and argon concentration in expired gas in man. 111 79

1. Eight patients who had suffered a fracture of one leg were studied before and after a 7 weeks period of rehabilitation during work with one leg and both legs on a bicycle ergometer. 2. In submaximal exercise minute ventilation for a given carbon dioxide output and tidal volume at a given minute ventilation remained unchanged throughout the period of therapy for both one- and two-leg exercise: oxygen intake for a given work output and cardiac frequency for a given oxygen intake decreased in both the injured and uninjured limb during one-leg work, although in two-leg exercise there was no significant change. 3. Oxygen intake at zero load was subtracted from the maximum oxygen intake measured during loaded exercise to give net values for each limb exercised separately or both legs exercised together. The net maximum oxygen intake thus calculated increased 8-9% (*17 1/min) in the uninjured leg and 17-4% (*29 1/min) in the injured leg during one-leg exercise. In two-leg exercise the increase was 17-2% (*43 1/min), which approximately equals the increase in the two legs measured separately. 4. In both legs there was an increase in leg muscle (plus bone) volume although this was significant in the injured leg only. 5. The maximum oxygen intake attained in two-leg exercise for a given leg volume in the patients at discharge was not significantly different from that found previously in a cross-sectional survey of young healthy (naval) servicemen. Thus the rehabilitation programme investigated appears to be effective, although the spontaneous recovery without a rehabilitation programme is unknown.
Clin Sci Mol Med 1975 Feb
PMID:Changes in physiological performance of the lower limb after fracture and subsequent rehabilitation. 111 30

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14-C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38 degrees C for 24 h in Krebs bicarbonate solution (pH 7-38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur "non-enzymatically".
Clin Sci Mol Med 1975 May
PMID:Factors affecting the metabolic production of methylguanidine. 112 27


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