Synthesis Of Human Hemoglobin Research Articles

WITHDRAWN: Recent Advances in the Microbial Synthesis of Human Hemoglobin

Hemoglobin is a major binding protein in human red blood cells and plays an important role in the storage and transportation of oxygen. In recent years, the use of recombinant hemoglobin as a new type of oxygen carrier has attracted widespread attention. So far, the research on recombinant hemoglobin technology is in its early stages and there are still many problems, such as low yield and easy degradation. In this review, we summarize the molecular strategies for recombinant synthesis of human hemoglobin in microorganisms through metabolic engineering and synthetic biology techniques in recent years, and explore the possibility of preparing hemoglobin-based oxygen carriers based on fetal hemoglobin, in order to improve the yield of recombinant human hemoglobin and the sustained stability during protein production through protein engineering strategies, and to possibly reduce the toxic side effects of recombinant hemoglobin products.

Genotype-phenotype characteristics of β thalassemia children in the Gaza Strip, Palestine

Genotype-phenotype characteristics of β thalassemia children in the Gaza Strip, Palestine Thalassemias are considered one of the most common known hereditary blood disorders in mankind, quantitatively affecting the synthesis of human hemoglobin. At least 60,000 severely affected individuals are born every year. Thalassemias have been encountered in practically every racial group and geographic location in the world; however, they are most common among individuals originating from tropical and subtropical regions. Thalassemias are classified based on the particular globin chain(s) that are produced in a reduced amount, so the main types of this inherited disorder which have been defined are α, β, δβ, δ, γδ β, and εγδβ thalassemias.

-(alpha)20.5 is the most frequent large deletion in the Puglia region of Italy.

The α-thalassemias are a heterogeneous group of inherited disorders, characterized by a reduced or absent synthesis of human hemoglobin (Hb) α chains. The α-thalassemia (α-thal) phenotype is produced by different genetic determinants, classified as deletional or nondeletional defects. To date, more than 16 α-thal deletions have been described (1); most of them, ranging in size from 5.2 to more than 100 kb, abolish the function of both α genes on the same chromosome. Extensive deletions are also located 5′ to the α-globin gene cluster, and nondeletional defects were also identified but less frequently than deletional ones (2,3).

Post-translational control of human hemoglobin synthesis The role of the differential affinity between globin chains in the control of mutated globin gene expression

The interactions between β-thalassemia and the humen hemoglobin (Hb) α-chain variants, Hb Hasharon, Hb O Indonesia and Hb J Paris, and between α-thalassemia and the β-chain variants, Hb S, Hb C and Hb G San José, which are characterized by preferential decrease of the abnormal Hb level in peripheral blood, have been studied. Both biosynthesis studies in reticulocytes and determination of the relative affinity of abnormal chains for normal complementary chains by in vivo recombination experiments, involving globin chains previously isolated in their native form, have been carried out in order to provide insights on the molecular events following the synthesis of the mutant chains under conditions of complementary chain deficiency. Furthermore, we have measured the relative affinity for complementary chain of β D Los Angeles - and α J Rovigo - chains , the level of which does not decay in thalassemic carriers, and of α Legnano - and β Osu Christiansborg - chains , which have not yet been observed in association with thalassemias. Our experiments indicated that the differential affinity for β-chains is not always the major post-translational control mechanism which regulates the level of certain α-chain variants in β-thalassemic heterozygotes, and that preferential removal of abnormal chains by proteolytic enzymes is likely to play an important role in most cases. On the other hand, the low affinity of certain variant β-chains for α-chains may offer an explanation for the low level of certain β-chain variants in peripheral blood of non-thalassemic carriers, as well as to their decrease under conditions of relative α-chain deficiency (α-thalassemias).

The molecular basis of disorders of human hemoglobin synthesis.

The structure and organization of the human globin genes at the nucleotide level has been established by restriction endonuclease digestion of cellular DNA, and by the isolation and purification of these genes in phage vectors. With this approach it has been possible to define alterations at the DNA level resulting in a group of inherited diseases of man known as the thalassemia syndromes, and related disorders. Combined with other known genetic and biochemical data, these studies provide a framework for understanding the pathogenesis of these disorders at the molecular level.

Defect in messenger RNA for human hemoglobin synthesis in beta thalassemia.

Functional messenger RNA for human hemoglobin synthesis was prepared from reticulocyte lysates of patients with homozygous beta thalassemia and sickle cell anemia. The messenger RNA stimulated the synthesis of human globin chains by a cell-free system derived from Krebs mouse ascites cells. In the presence of beta thalassemia messenger RNA, the system synthesized much less beta chain than alpha chain whereas in the presence of sickle cell anemia messenger RNA, nearly equal amounts of alpha and beta chains were synthesized. The beta/alpha synthetic ratios obtained in the cell-free system were similar to those obtained by incubating intact beta thalassemia and sickle cell anemia reticulocytes in the presence of radioactive leucine. The experiments provide direct evidence of a defect in messenger RNA for beta chains as a cause for the decreased synthesis of beta chains observed in beta thalassemia.

Hemoglobins, Haptoglobins, and Transferrins in Man

lapped. The distribution of genes within a population, and the differences in the frequency of their alleles which characterize one population and distinguish it from another, need not be considered trivial if selection plays a part in determining them. A search for additional loci as aids in classification may be sterile and boring; but a quest for the sources of human variation and the analysis of the interactions of genetic and ecological factors stimulates continuing interest. Recently accumulated evidence indicates that some, and perhaps most, aspects of polymorphism in man are adaptive and that cultural factors are commonly involved in the process of adaptation. By their joint efforts cultural and physical anthropologists are in a position to contribute to a deeper understanding of those factors which have made us what we are today. Such collaboration is dependent upon the degree of communication established between scholars in these two facets of anthropology. The student of human biology needs to hear frequently about recent advances in the analysis of culture, and especially of cultural practices which affect the genetic structure or phenotypic appearance of different populations. In return, new developments in human biology should be brought to the attention of anthropologists in general. Significant among such advances is the understanding of the structure, function, and inheritance of various protein fractions of the blood. A number of these are inherited in simple Mendelian manner and thus lend themselves readily to genetic analysis. As they occur in varying frequencies among different human populations, they can, like the blood types, suggest the degree of ancestral relationships between them. Like the blood types, too, their variety demonstrates the widespread extent and probable utility of balanced polymorphism in the human species. In 1949 when Neel established the genetic mechanism for sickle cell trait and sickle cell anemia and Pauling et al. (1949) demonstrated the electrophoretic difference between normal and sickle cell hemoglobin, doors were opened to unique research opportunities in genetics, biophysics, biochemistry, medicine, and anthropology. The past dozen years have witnessed vast strides in the understanding of the structure of the hemoglobin molecule, the strategy of the gene in producing its end product in the individual, and the ebb and flow of genes in the course of human history.