Hemoglobin switching in sheep and goats: occurrence of hemoglobins A and C in the same red cell

Sheep and goats switch from the synthesis of hemoglobin A (alpha(2)beta(2)(A)) to hemoglobin C (alpha(2)beta(2)(C)) when made anemic. We have demonstrated the existence of the asymmetrical hybrid hemoglobin, alpha(2)beta(A)beta(C), in the circulating red cells of anemic sheep. These erythroid cells, therefore, synthesized both A and C hemoglobin simultaneously. Thus, the switch appears to be mediated by selective gene expression rather than by a clonal or cellular selective mechanism.     

Rabbit hemoglobin biosynthesis: use of human hemoglobin chains to study molecule completion

A cell-free protein-synthesizing system made from rabbit reticulocytes was used to incorporate (14)C-amino acids into hemoglobin. Electrophoretic analyses of the soluble products of this cell-free system revealed a fraction containing rabbit (14)C-alpha chains in addition to the rabbit (14)C-hemoglobin. The addition of isolated human hemoglobin beta chains to this system during active synthesis inhibited the release of newly synthesized rabbit (14)C-beta chains into solution from the ribosome fraction. This inhibition was possibly a result of hybrid hemoglobin formation between rabbit alpha and human beta chains. A model of hemoglobin construction in which soluble alpha chains are intermediates is suggested. These alpha chains may aid in the release of beta chains from the polyribosomes during the completion of the hemoglobin molecule.     

Hemoglobin interaction: modification of solid phase composition in the sickling phenomenon

Direct analyses of solid phase formed by deoxygenating solutions of sickle-cell hemoglobin (Hb S) in the presence of certain other hemoglobin species show that hemoglobins A and C can participate in the filamentous fine structure characteristic of the sickling phenomenon. In contrast, fetal hemoglobin (Hb F) is nearly completely excluded.     

Hemoglobin types of Macaca irus and Macaca mulatta monkeys

Hemoglobin of 30 Macaca mulatta monkeys and of 15 Macaca irus monkeys consisted of one electrophoretic component similar to human hemoglobin A. Twenty-one M. irus monkeys had two types of hemoglobin. In 20 animals the hemoglobin resembled human hemoglobin AJ, and in one animal it resembled human hemoglobin AI.     

Hemoglobin Portland 1: a new human hemoglobin unique in structure

A new hemoglobin (Hb), Portland 1, has been found in a newborn infant having multiple congenital anomalies and complex autosomal chromosomal mosaicism. The new hemoglobin has a unique tetrameric structure (molecular weight, 66,000) composed of two pairs of different types of chains, neither of which is alpha, gamma(2)x(2). The x-chain of Hb Portland 1 may be a new type of hemoglobin chain, but the available evidence suggests that it may be identical with the epsilon chain. We suggest that Hb Portland 1 is an embryonic hemoglobin that persisted until after birth in relatively large amounts in this patient.     

Activation of hemoglobin C synthesis in sheep marrow culture

Erythropoietin preferentially stimulates hemoglobin C synthesis in suspension cultures of marrow cells from sheep homozygous for hemoglobin A; the amount of synthesis is dependent on the dose of erythropoietin and is blocked by antiserum to erythropoietin. The results provide the first in vitro evidence that erythropoietin mediates the hemoglobin A --> C "switch" in sheep and indicate that bone marrow cultures may be used to investigate the mechanisms involved in the preferential gene activation characteristic of the hemoglobin A --> C system.     

Hemoglobin Freiburg: abnormal hemoglobin due to deletion of a single amino acid residue

Structural characterization of a new variant of human hemoglobin (adult), designated hemoglobin Freiburg, indicates the deletion of the valyl residue No. 23 from an otherwise normal beta-chain. The formula may be written (alpha2)beta(2)(23val-0). The abnormal hemoglobin is present with hemoglobin A in the proposita and in two of her three living children, but is not detectable in her parents. We postulate that this variant represents a triplet base deletion which most likely resulted from an unequal crossing-over between two normal betachain loci during meiosis in one of the parents of the proposita.     

Heme and globin synthesis control: observations in vivo in beta thalassemia

After administration of glycine-2-(14)C to a patient with thalassemia, the specific activities of heme and globin of F hemoglobin were consistently higher than those of hemoglobin A. After reaching a maximum, the ratio of the specific activity of heme to that of globin remained constant within each hemoglobin. Explanations considered include dilution by preformed subunits, differential turnover of hemoglobins, and possibly more than one heme-synthesizing pool.     

Adult hemoglobin synthesis by reticulocytes from the human fetus at midtrimester

The synthesis of adult-type hemoglobin was measured in small samples of peripheral blood cells from 9- to 18-week human fetuses. Hemoglobin indistinguishable from hemoglobin A was identified by ion-exchange chromatography, electrophoresis at pH 8.6, tryptic peptide analysis, and the insensitivity of its synthesis to the action of O-methylthreonine. Synthesis of hemoglobin A accounted for 8 to 14 percent of total hemoglobin synthesis and was demonstrated in as little as 10 microliters of fetal blood. These studies provide sensitive methods for the detection of beta chain types in hemoglobin synthesized by the human fetus at midtrimester. If methods to obtain small quantities of fetal blood at midtrimester become available, these techniques should be applicable to the antenatal detection of sickle cell anemia and related hemoglobinopathies.     

Hemoglobin in a nonleguminous plant, parasponia: possible genetic origin and function in nitrogen fixation

A dimeric hemoglobin was purified from nitrogen-fixing root nodules formed by association of Rhizobium with a nonleguminous plant, Parasponia. The oxygen dissociation rate constant is probably sufficiently high to allow Parasponia hemoglobin to function in a fashion similar to that of leghemoglobin, by oxygen buffering and transport during symbiotic nitrogen fixation. The identification of hemoglobin in a nonlegume raises important questions about the evolution of plant hemoglobin genes.     

Hemoglobin Hijiyama: a new fast-moving hemoglobin in a Japanese family

A variant of hemoglobin A, named Hb Hijiyama, found in two generations of a Japanese family living in Hiroshima, Japan, has a higher anodal electrophoretic mobility than hemoglobin A; a gain of two negative charges per molecule is indicated. Fingerprinting and amino acid analysis showed the biochemical anomaly to be in the beta chain at residue 120, where lysine is replaced by glutamic acid. In the heterozygote carriers of the abnormal hemoglobin there is no apparent association with clinical or hematologic abnormalities.     

Synthesis of functional human hemoglobin in transgenic mice

Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.     

Thermal Vent Clam (Calyptogena magnifica) Hemoglobin

A heterodont bivalve mollusk Calyptogena magnifica, from the East Pacific Rise and the Galápagos Rift hydrothermal vent areas, contains abundant hemoglobin in circulating erythrocytes. No other known heterodont clam contains a circulating intracellular hemoglobin. The hemoglobin is tetrameric and has a relatively high oxygen affinity, which varies only slightly between 2 degrees and 10 degrees C. The presence of hemoglobin in the clam may facilitate the transport of oxygen to be used in chemoautotrophic hydrogen sulfide metabolism.     

Hemoglobins A and A2 in New World primates: comparative variation and its evolutionary implications

Hemoglobin A(2) (alpha(2)delta(2)) in New World primates represents about 1/160 to 1/16 of total hemoglobin and, by virtue of this low proportion, is presumed to be functionally unimportant. Nonetheless, A(2) exhibits genetic polymorphism by electrophoresis in three out of five genera, whereas the major component, hemoglobin A (alpha(2)beta(2)), is electrophoretically invariant. Moreover, in four genera, including man, the evolutionary accumulation of mutations has been greater in delta than in beta Such findings suggest that both polymorphism and evolutionary changes can accrue to an effectively functionless and thus selectively nearly netutral gene.     

Hemoglobin Gun Hill: deletion of five amino acid residues and impaired heme-globin binding

Hemoglobin Gun Hill, a new variant of adult hemoglobin, was found in a Caucasian and one of his three daughters. The abnormal hemoglobin had only half of the expected number of heme groups. Five amino acid residues appeared to be missing from the beta-globin chains. These residues occur in linear sequence in normal beta-chains in a region involved in heme-globin binding. A deletion of five amino acids in the beta-chains of hemoglobin Gun Hill is postulated. The most likely mechanism for the origin of such a hemoglobin variant would appear to be unequal crossing-over during meiosis.     

Electrophoresis of hemoglobin in single erythrocytes

A technique for electrophoretic analysis of the hemoglobin mixtures from single erythrocytes has been developed. Hemoglobin mixtures were separated into their constituents, A(2), A, C, S, and J, at least qualitatively.     

Biosynthesis of hemoglobin Ann Arbor: evidence for catabolic and feedback regulation

Hemoglobin Ann Arbor, in which arginine replaces leucine in position 80 of the a chain, occurs in aflected individuals in low proportion to hemoglobin A. Biosynthetic studies were perforined on reticulocytes of a patient heterozygous for this hemoglobin. These studies suggested that the low percentage of hemoglobin Ann Arbor is prinlarily due to preferential destruction of the abnormal component. The reduced concentration of alpha Ann Arbor chains was also reflected in a decreased synthesis of normal beta chains.     

Lack of abnormal hemoglobins in Alaskan Eskimos,Indians, and Aleuts

In an examination of the blood of 708 Eskimos, 200 Aleuts, and 44 Indians in Alaska for abnormal types of hemoglobin, only normal hemoglobin A was detected. It may be concluded that abnormal hemoglobins in these races are rare if they occur at all.     

Hemoglobin kinetics and the effect of organic phosphates

A kinetic model based on allosteric mechanisms of cooperativity fits the experimentally observed phosphate dependence of hemoglobin reactions. Subunit inequivalence is found to be important in analyzing hemoglobin kinetics. The observed increase in the rate of deoxygenation in the presence of organic phosphates is primarily related to the increased rate of dissociation of the second oxygen molecule.     

Hemoglobin Sphakiá: a delta-chain variant of hemoglobin A2 from Crete

A new variant of the normal minor component Hb A(2) has been detected in a family that lives in Sphakiá, Crete. Chemical studies of this abnormal hemoglobin, designated Hb A(2) delta Sphakiá, indicates a substitution of the histidyl residue number two of the delta-chain by an arginyl residue.