Hemoglobin elucidation

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

This theory clearly predicts that the shape of the polymer length distribution curve determines the shape of the time course of depolymerization. For example Kristofferson et al. (1980) were able to show that apparent first-order depolymerization kinetics arise from length distributions which are nearly exponential. It should also be noted that the above theory helps one to gain a better feeling for the time course of cytoskeleton or mitotic apparatus disassembly upon cooling cells to temperatures which destabilize microtubules and effect unidirectional depolymerization. Likewise, the linear depolymerization kinetic model could be applied to the disassembly of bacterial flagella, muscle and nonmuscle F-actin, tobacco mosaic virus, hemoglobin S fibers, and other linear polymers to elucidate important rate parameters and to test the sufficiency of the end-wise depolymerization assumption in such cases. 

Early isotope tracer experiments by David Shemin permitted the elucidation of the formation of the immediate precursor of the porphyrin needed for the cytochromes and for hemoglobin. These studies indicated that the glycine methylene carbon and nitrogen were incorporated along with both carbons of acetate. Subsequent enzymatic studies in both bacteria and animals revealed a condensation reaction between succinyl-CoA and glycine to yield 5-amino-levulinate and C02 (presumably by way of an enzyme-bound /3-keto acid, a-amino-/3-ketoadipate) (fig. 22.13). 

Apart from hemoglobin, various other proteins have been shown to be glycosylated by one of the methods described above. With the exception of insulin and albumin, however, the specific glyco-sylation sites remain to be elucidated. 

In view of the high affinity of arsenic for thiol functions, it can be expected that lewisite and CVAA will bind to cysteine residues of proteins. When human blood was incubated with 20 nM to 0.2 mM of [14C]lewisite, 25-50% of the dose became associated with globin (35). Electrospray tandem MS provided evidence for the presence of a CVAA-crosslink between the cysteine-93 and cysteine-112 residues in fi-globin. Whether this was the only type of adduct has not yet been completely elucidated. It must be remarked, however, that this result was in contrast with results obtained by others for the analogous phenyldichloroarsine, for which binding to human hemoglobin could not be observed. 

Streptomyces distallicus the structure elucidation and synthesis have also been made by them.165 A wide variety of porphyrins which are derivatives of porphin (125 R = H) occur in nature and exert three biological functions (a) oxygen storage and transport, as in hemoglobin, (b) cellular respiration as in the cytochromes, and (c) photosynthesis, as in the chlorophylls for detailed discussion of structures and synthesis of naturally occurring porphyrins, see references.166 Recent developments in the chemistry of polypyrrolic compounds have been reviewed.167 Several naturally occurring indole alkaloids have dimeric structures of type B,168 an example of which is c-toxiferine-I, a calabash curare alkaloid found in South American species of Strychnos.169... 

A titration curve for sperm whale myoglobin has been reported by Bres-low and Gurd (1962). The most striking feature is that it exhibits a time-dependent acid denaturation, which resembles that observed for the similar protein hemoglobin. To elucidate the physical nature of this reaction, emphasis was placed on the back titration to neutral pH of denatured protein. As in the case of hemoglobin (mentioned earlier), there are two major differences between the titration curves of native and denatured myoglobin, as shown by the data of Table XV. 

The combination of metal ion, ligand and chemical environment (sudi as solvent or polymer) determines the chemical and physical properties of the metal dielates. Biological metal porphyrins occuring in hemoglobin, chlorophyll, vitamin B12 and some metallo-enzymes show this extremly well. Model systems seems to be useful in order to elucidate th f ors and to construct artificial systems for practical use. 

The chemical structure of sulfhemogiobin (SHb), a green hemoglobin derivative, has not yet been completely elucidated. The central iron atom is in the ferrous state. Combination of SHb with CO to SHbCO has been encountered (V2). The structure proposed by Nijveld (N2) for the a-methene group in the porphyrin ring,... 

After World War II Pauling studied sickle cell anemia, and theorized that it was the result of a genetically based defect in the patient s hemoglobin molecules. In 1949 he and Harvey Itano confirmed this theory they had identified what they called a molecular disease, one that could be defined by a molecular abnormality. In 1954 Pauling received the Nobel Prize in chemistry for his research on the chemical bond and its appfication to the elucidation of the structure of complex substances. ... 

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