Haemoglobin molecules

Red blood cells are amongst the most numerous of the human cell lines an average healthy 70 kg male having a total of approximately 25 x cells in his 51 of blood. A typical red cell contains in excess of 600 million haemoglobin molecules which equates to a total of about 300 g of haemoglobin, an amount that is far greater than for any other protein in the body. The lack of a nucleus clearly indicates that red cells cannot divide and at the end of their life, worn out RBCs are removed by the cells of the reticuloendothelial system. Approximately 2% (5 x 1011) of the red cell number are removed and replaced by new ones each day. Haem synthesis is outlined later in this chapter and its catabolism is discussed in Chapter 6. 

The concentration of BPG is the same as that of haemoglobin and the position where the BPG is bound to the haemoglobin molecule has been identified from the 3-dimensional structure. 

Pyridoxal 5 -phosphate (a derivative of pyridoxal vitamin Bg) is similar in size and charge to 2,3-DPG. Covalent attachment of pyridoxal 5 -phosphate reduces the oxygen affinity of the haemoglobin molecule. Covalent attachment of benzene isothiocyanates to the amino termini of the four haemoglobin polypeptide chains, also yields derivatives which display lower oxygen affinity. These may prove worthy of clinical investigation. 

Physiologically, there is an orderly sequence observed from birth to adulthood in the genetically regulated production of the different globins that make up the haemoglobin molecule. Furthermore, the assembly of the a and fi chains is precisely balanced. 

They can be classified into three main groups, haemoglobin solutions in which the haemoglobin molecule has undergone a modification, liposome-encapsulated haemoglobin, and perfluorocarbons. All of them have intravascular half-lives that are relatively short in comparison to that of transfused erythrocytes. 

The Shannon-Prewitt tabulation also distinguishes between different spin states for ions of the transition elements. For example, the radius of Fe2+ in octahedral six-coordination is 17 pm smaller for the low-spin state as opposed to high-spin. If you study bio-inorganic chemistry in a more advanced text, you will find that this fact is of great importance in understanding the mechanics of the haemoglobin molecule (see Section 9.8). 

The haemoglobin molecule (Hb) has a molecular weight of about 64000. Four subunits can be identified, each consisting of a polypeptide chain to which is attached a porphyrin group (Fig. 8.6), with an iron atom near its centre. The iron atom is in the II oxidation state (high-spin d6) and is further bonded to a nitrogen atom from an amino-acid residue below the porphyrin ring. The conformation of the polypeptide chain prohibits... 

Finally, the iron compound haem, part of the haemoglobin molecule we use to carry oxygen around in our bloodstream. It contains the aromatic porphyrin ring system with its eighteen elec-trons arranged in annulene style. Chlorophyll, mentioned earlier in this chapter, has a similar aromatic ring system. 

Red blood cells are composed of haemoglobin. Glucose sticks to the haemoglobin to make a glycosylated haemoglobin molecule (HbAlc). The more glucose present in the blood, the more HbAlc will be present. 

FIGURE 7.43 The haem moiety of the haemoglobin molecule showing the binding of the oxygen molecule to the iron atom. As shown in the diagram, carbon monoxide binds at the same site. His=side chain of the amino acid histidine. From Timbrell, J.A., Introduction to Toxicology. Taylor and Francis, London, 1989. 

To give some idea of the sizes involved here, the diameter of a human blood cell is about 7500 nm (7.5 (im), that of an individual haemoglobin molecule is about 2.8 nm and that of an oxygen molecule is about 0.16 nm (see Table 1.1). 

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