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At least 19 recordsLinked to original sources
PubMed1977

The hemoglobins of Artemia salina. IV. A model for genetic control of hemoglobin 1, hemoglobin 2, and hemoglobin X.

Two loci account for all genetic variation resulting in difference in electrophoretic mobility in three hemoglobins (Hb1, Hb2, and HbX) in the hemolymph of the brine shrimp. Four alpha alleles and nine beta alleles have been studied. In shrimps of all genotypes and in electrophoresis in media with varying degrees of molecular sieving, Hb2 is approximately equidistant from Hb1 and HbX. A shrimp heterozygous at both loci has a three-banded Hb1, a four-banded Hb2, and a three-banded BbX. We conclude that Hb2 contains n alpha-polypeptides and n beta-polypeptides. Hb1 contains 2n alpha-polypeptides. HbX contains 2n beta-polypeptides. During electrophoresis, the three native hemoglobins undergo reversible dissociation to n subunits. Subunits with the same charge reassemble to migrate as molecules of the same size as the native molecules. Although there is no evidence for an additional polypeptide in the three hemoglobins, we cannot exclude such a possibility. If it exists, it is under three constraints: (1) it must be present in equal amounts in each of the three hemoglobins; (2) it must have the same molecular weight as the alpha- and beta-polypeptides; and (3) it must be free of genetic variation (detectable by electrophoresis).

Alleles↗
PubMed1977

The hemoglobins of Artemia salina. V. Genetic variation in hemoglobin 1, hemoglobin 2, and hemoglobin 3.

Electrophoretic mobilities of three hemoglobins (Hb1, Hb2, and Hb3) were studied in 15 populations of brine shrimps. Genetic segregation data support the model that Hb2 contains n alpha-polypeptides and n beta-polypeptides; Hb1 contains 2n alpha-polypeptides- Hb3 contains neither alpha- nor beta-polypeptides. There is no evidence of linkage of alpha and beta loci with each other or with the locus (or loci) which governs Hb3 or with the nonhomologous portion of the sex chromosomes. Hemoglobins of different populations may be hybridized in vitro by incubation at high temperature. Reversible dissociation to subunits which contain only one (alpha or beta) polypeptide occurs at 40 C (for Hb1) and at 50 C (for Hb2).

Alleles↗
PubMed1979

Low proportions of glycosylated hemoglobin associated with hemoglobin S and hemoglobin C.

Using a cation-exchange chromatographic method, we found normal or subnormal values for glycosylated hemoglobin in a few diabetic patients with persistent hyperglycemia. Subsequent investigations revealed that these unexpected results had originated from black patients with diabetes. In view of common occurrence of abnormal hemoglobins in the Negro population, we subjected blood preparations to electrophoresis on cellulose acetate and acrylamide gel. The results have shown the presence of hemoglobin S or hemoglobin C in each patient. When allowance was made for the percentage of the abnormal hemoglobin, the "corrected values" of glycosylated hemoglobin increased to the diabetic range. Furthermore, the corrected values agreed well with the "expected values" calculated from a regression line correlating fasting blood glucose concentrations and proportions of glycosylated hemoglobin in more than 300 diabetics with no evidence of hemoglobinopathy. We conclude that in diabetic patients presenting with hemoglobin S or hemoglobin C, there is a considerable decrease in the values for glycosylated hemoglobin as measured by cation-exchange chromatographic methods, and that this decrease is proportional to the percentage of the abnormal hemoglobin.

Blood Glucose↗
PubMed1976

Hemoglobin pyrgos alpha2 beta2 83 (EF7) Gly leads to Asp: a new hemoglobin variant in double heterozygosity with hemoglobin S.

An electrophoretically fast-moving hemoglobin variant was found to be present together with hemoglobin S, in the hemolysate of the rythrocytes of at 3-yr-old Greek boy. Electrophoresis of the parents' erythrocyte hemolysates revealed that the father was an AS heterozygote, while the mother was a carrier of the variant hemoglobin. A sibling was also found to be a carrier. The amount of the mutant hemoglobin in the peripheral blood of the propositus, his mother, and his brother was 62.2%, 52.5%, and 51.1%, respectively, as determined by column chromatography. The patients peripheral blood smear showed mild anisocytosis, microcytosis, and hypochromia. Similar but less pronounced red cell abnormalities were found in the other two carriers. Structural analysis of the variant hemoglobin revealed substitution of an aspartic acid for the glycine residue at the beta83 (EF7) position. This new hemoglobin was named hemoglobin Pyrgos. All the carriers of hemoglobin Pyrgos are clinically healthy, and there seems to be no interaction between hemoglobin Pyrgos and hemoglobin S as manifested clinically.

Amino Acids↗
PubMed1978

Oxidation-reduction reactions of hemoglobin A, hemoglobin M Iwate, and hemoglobin M Hyde Park.

The kinetics and equilibrium of the redox reactions of hemoglobin A, hemoglobin M Iwate, and hemoglobin M Hyde Park using the iron (II) and iron (III) complexes of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetate (CDTA4-) as the reducing and oxidizing agents have been studied. With respect to the equilibrium it was found that hemoglobin M Iwate (where the beta chains were reduced) was more readily reduced than hemoglobin M Hyde Park (where the alpha chains are reduced). This difference was shown to be a result of a difference in the rate constant for reduction but not oxidation. The observed rate contants for the reduction of all three hemoglobins were shown to decrease with increasing pH. This was attributed to a decrease in the [T]/[R] ratio. The observed rate contants for the oxidation reaction were shown to increase with increasing pH. Accompanying this increase was a change in the kinetic profile for hemoglobin A from pseudo first order to one in which the rate increased as the extent of reaction increased. Inositol hexaphosphate had no effect on the rate of oxidation of deoxyhemoglobin A. This was a result of binding of FeCDTA2- or HCDTA3- to the protein. However, in the presence of inositol hexaphosphate, the reduction of methemoglobin A exhibited biphasic kinetics. This result was interpreted in terms of the production of a small amount of a conformation which was more readily reduced.

Hemoglobin A↗
PubMed1975

The effects of inositol hexaphosphate on the allosteric properties of two beta-99-substituted abnormal hemoglobins, hemoglobin Yakima and hemoglobin Kempsey.

Hemoglobins (Hb) Yakima and Kempsey were purified from patients' blood with diethylaminoethyl cellulose column chromatography. The oxygen equilibrium curves of the two hemoglobins and the effects of organic phosphates on the function were investigated. In 0.1 M phosphate buffer, Hill's constants n for Hb Yakima and Hb Kempsey were 1.0 to 1.1 at the pH range for 6.5 to 8.0 and the oxygen affinities of both the mutant hemoglobins were about 15 to 20 times that of Hb A at pH 7.0. The Bohr effect was normal in Hb Yakima and one-fourth normal in Hb Kempsey. In the presence of inositol hexaphosphate, the oxygen affinities to Hb Yakima and Hb Kempsey were greatly decreased, and an interesting result revealed that these hemoglobins showed clear cooperativity in oxygen binding. Hill's constant n in the presence of inositol hexaphosphate was 1.9 for Hb Kempsey and 2.3 for Hb Yakima at pH 7.0. The cooperativities of these mutant hemoglobins were pH-dependent, and Hb Kempsey showed high cooperativity at low pH (n equal 2.1 at pH 6.6) and low cooperativity at high pH (n equal 1.0 at pH 8.0). Hb Yakima showed similar pH dependence in cooperativity. In the presence of inositol hexaphosphate, Hb A showed a pH-dependent cooperativity different from those of Hb Yakima and Hb Kempsey, namely, Hill's n was the highest in alkaline pH (n equal 3.0 at pH 8.0) and decreased at lower pH (n equal 1.5 at pH 6.5). 2,3Diphosphoglycerate bound with the deoxygenated Hb Yakima and Hb Kempsey, however, had no effect on the oxygen binding of these abnormal hemoglobin. The pH-dependent cooperativity of alpha1beta2 contact anomalous hemoglobin and normal hemoglobin was explained by the shifts in the equilibrium between the high and low ligand affinity forms.

Allosteric Regulation↗
PubMed1975

Allosteric interactions in non-alpha chains isolated from normal human hemoglobin, fetal hemoglobin, and hemoglobin Abruzzo (beta143 (H21) His replaced by Arg).

Oxygen-linked effects of inositol hexaphosphate occur in heme-containing non-alpha chains isolated from normal human hemoglobin, fetal hemoglobin, and the abnormal human hemoglobin Abruzzo, beta143(H21) His leads to Arg. The occurrence of these effects implies that the chains undergo ligand-linked conformational changes. Inositol hexaphosphate lowers the oxygen affinity of isolated beta and gamma chains by differential binding to their deoxy conformations. Neither 2,3-diphosphoglycerate nor inorganic phosphate produces such an effect. In the case of Abruzzo beta chains, the binding of inorganic phosphate and 2,3-diphosphoglycerate is also oxygen-linked. Stripped beta chains isolated from hemoglobin Abruzzo have much higher oxygen affinity than beta chains isolated from HbA. Their higher oxygen affinity and enhanced allosteric interactions with phosphates account, in large part, for the abnormal functional behavior of the hemoglobin Abruzzo tetramer. In this hemoglobin variant the substitution of arginine for histidine at beta143 involves a residue known to interact with anionic allosteric effectors of hemoglobin. It is of interest that the effect of inositol hexaphosphate observed with isolated gamma chains is comparable to the effect observed with isolated beta chains, even though the gamma143 position is occupied by an uncharged serine residue.

Allosteric Regulation↗
PubMed1976

Hemoglobin Hope: studies of oxygen equilibrium in heterozygotes, hemoglobin S-Hope disease, and isolated hemoglobin Hope.

Hemoglobin Hope (beta(H14)136gly leads to asp), a mildly unstable variant, was found to have decreased oxygen affinity, a normal Bohr effect and diminished cooperativity. Decreased oxygen affinity of hemoglobin Hope may explain the previous failure to find an appropriate response to hemolysis in individuals studied who were heterozygous for both hemoglobin Hope and sickle hemoglobin. Salt bridge formation between NA1 valine and H14 aspartic acid may stabilize the beta Hope subunit in its deoxy form thus producing intrinsically low oxygen affinity and reduced cooperativity.

Diphosphoglyceric Acids↗
PubMed1976

Screening for abnormal hemoglobins in the middle east: new data on hemoglobin S and the presence of hemoglobin C in Saudi Arabia.

48 of 391 apparently healthy adult Saudi males had an AS hemoglobin pattern on electrophoresis, four subjects had an S pattern, and two subjects AC. A dithionite screening test lacked sensitivity and specificity in detecting hemoglobin S under the conditions of this study. A sickle cell trait frequency of 0.123 evidenced by hemoglobin electrophoresis correlates closely with previous studies of hemoglobinopathies in Saudi Arabs. The presence of four subjects with sickle cell disease in the study group provides further evidence of the "benign" nature of sickle cell disease in Saudi Arabia.

Adolescent↗
PubMed1975

A double heterozygous hemoglobin. Hemoglobin OIndonesia and hemoglobin DPunjab in an individual.

During surveys for abnormal hemoglobins in Iran, an individual was found to have four electrophoretically distinct hemoglobins. The abnormality was found only in the father of the propositus, in two of the father's sisters, and in three brothers and sisters of the propositus. Investigations revealed that the four hemoglobin components are the result of a double heterozygosity between an alpha-chain variant (Hb OIndonesia) and a beta-chain variant (Hb DPunjab). The presence of the abnormal hemoglobins was not associated with hemolytic disorders or obvious clinical symptoms.

Blood Protein Electrophoresis↗
PubMed1975

Two new hemoglobins. Hemoglobin Alabama (beta39(C5)Gln leads to Lys) and hemoglobin Montgomery (alpha 48(CD 6) Leu leads to Arg).

The amino acid substitutions in two new hemoglobins found by electrophoretic screening during a survey in Alabama have been determined by column chromatography and amino acid analyses of their tryptic peptides. They are hemoglobin Alabama (beta 39(C 5)Gln leads to Lys) and hemoglobin Montgomery (alpha 48(CD 6) Leu leads to Arg). No harmful symptoms have been attributed to the presence of either hemoglobin.

Adult↗
PubMed1979

Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S.

We have previously found that the inhibitory effect of hemoglobin F (Hb F) on the polymerization of Hb S proceeds via the formation of asymmetrical hybrid tetramers of the type alpha2betasgamma. Examination of the gelling properties of binary mixtures of Hb S and several Hb variants now shows that, among the gamma chain amino acid residues that differ from those of the beta chain, residues gamma80 (EF4) and gamma87 (F3) are at least partly responsible for this inhibition. Furthermore, we find that mixing Hb A2(alpha2delta2) with Hb S strongly inhibits gelling to an extent similar to that seen with Hb S/Hb F mixtures; this inhibition is attributable to amino acid differences between the delta and beta chain sequences at positions delta22 (B4) and delta87 (F3). Therefore, residues 22, 80, and 87 of the beta chain appear to be involved in intermolecular contact sites that stabilize the deoxy Hb S polymers.

Amino Acid Sequence↗
PubMed1975

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin.

Adult↗
PubMed1976

Studies on camel hemoglobin. 1. Physico-chemical properties and some structural aspects of camel hemoglobin (Camelus dromedarius).

Hemoglobin from an adult camel (Camelus dromedarius) was prepared from the red cell lysate by CM- and DEAE-cellulose chromatography. The purified hemoglobin showed a lesser mobility on starch gel electrophoresis at pH 8.5 than that of human hemoglobin C. Native camel hemoglobin contains 95-99% alkali-resistant hemoglobin and in soluble in 2.94 M K2HPO4/KH2PO4 buffer. Different forms of camel hemoglobin show similar ammonium sulfate precipitation curves. Indirect evidence for the stability of camel hemoglobin solutions was obtained from several sources. Spontaneous met-hemoglobin formation is extremely slow and minimal quantities of degradation products appear on starch gel electrophoresis and on chromatographic separation. The alpha and beta chains of camel hemoglobin A were separated on a CM-23 column by the use of a pyridine formate gradient. Large peptide fragments were obtained by tryptic digestion of maleylated alpha and beta chains. The N-terminal structure of the alpha and beta chains and of tryptic maleylated peptides derived from alpha and beta chains are presented. Between adult camel hemoglobin and adult human hemoglobin six amino acid differences in the N-terminal 20 amino acid residues of the alpha chain, at residues: 4, 5, 12, 14, 17, and 19; eight amino acid substitutions were found in the beta chain at positions: 4, 5, 6, 9, 12, 13, 16, and 19. Substitutions at alpha5 Ala leads to Lys, and beta19 Asn leads to Lys, increase the net positive charge of camel hemoglobin by two, while other substitutions result in no charge differences. The molecular basis of the stability of camel adult hemoglobin is discussed.

Amino Acid Sequence↗
PubMed1976

Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins.

Oxidation studies of hemoglobin by Cu(II) indicate that for horse hemoglobin, up to a Cu(II)/heme molar ratio of 0.5, all of the Cu(II) added is used to rapidly oxidize the heme. On the other hand, most of the Cu(II) added to human hemoglobin at low Cu(II)/heme molar ratios is unable to oxidize the heme. Only at Cu(II)/heme molar ratios greater than 0.5 does the amount of oxidation per added Cu(II) approach that of horse hemoglobin. At the same time, binding studies indicate that human hemoglobin has an additional binding site involving one copper for every two hemes, which has a higher copper affinity than the single horse hemoglobin binding site. The Cu(II) oxidation of human hemoglobin is explained utilizing this additional binding site by a mechanism where a transfer of electrons cannot occur between the heme and the Cu(II) bound to the high affinity human binding site. The electron transfer must involve the Cu(II) bound to the lower affinity human hemoglobin binding site, which is similar to the only horse hemoglobin site. The involvement of beta-2 histidine in the binding of this additional copper is indicated by a comparison of the amino acid sequences of various hemoglobins which possess the additional site, with the amino acid sequences of hemoglobins which do not possess the additional site. Zn(II), Hg(II), and N-ethylmaleimide (NEM) are found to decrease the Cu(II) oxidation of hemoglobin. The sulfhydryl reagents, Hg(II) and NEM, produce a very dramatic decrease in the rate of oxidation, which can only be explained by an effect on the rate for the actual transfer of electrons between the Cu(II) and the Fe(II). The effect of Zn(II) is much smaller and can, for the most part, be explained by the increased oxygen affinity, which affects the ligand dissociation process that must precede the electron transfer process.

Animals↗