For hemoglobin

A system of internal iron exchange exists which is dominated by the iron required for hemoglobin synthesis. For formation of red blood cells, iron stores can furnish 10—40 mg/d of iron, as compared to 1—3 mg from dietary sources (74). Only ca 10 wt % of ingested iron actually is absorbed. 

Purification. Hemoglobin is provided by the red blood ceU in highly purified form. However, the red ceU contains many enzymes and other proteins, and red ceU membranes contain many components that could potentially cause toxicity problems. Furthermore, plasma proteins and other components could cause toxic reactions in recipients of hemoglobin preparations. The chemical modification reactions discussed herein are not specific for hemoglobin and may modify other proteins as well. Indeed, multifimctional reagents could actually couple hemoglobin to nonhemoglobin proteins. 

FIGURE 15.36 The structure, in ionic form, of BPG or 2,3-bisphosphoglycerate, an important allosteric effector for hemoglobin. 

That is, the situations for myoglobin and hemoglobin differ therefore, P50 and K cannot be equated for Hb because of its multiple, interacting, Oa-binding sites. The relationship between and P50 for hemoglobin, by use of Equation (A15.12), becomes... 

The 02-binding curve for myoglobin is hyperbolic, but for hemoglobin it is sigmoidal, a consequence of cooperative interactions in the tetramer. Cooperativ-ity maximizes the ability of hemoglobin both to load O2 at the PO2 of the lungs and to deliver O2 at the PO2 of the tissues. 

The protein that stores iron in the body is called ferritin. A ferritin molecule consists of a protein coat and an iron-containing core. The outer coat is made up of 24 pol3q5eptide chains, each with about 175 amino acids. As Figure 20-27 shows, the pol q5eptides pack together to form a sphere. The sphere is hollow, and channels through the protein coat allow movement of iron in and out of the molecule. The core of the protein contains hydrated iron(HI) oxide, FC2 O3 H2 O. The protein retains its shape whether or not iron is stored on the inside. When filled to capacity, one ferritin molecule holds as many as 4500 iron atoms, but the core is only partially filled under normal conditions. In this way, the protein has the capacity to provide iron as needed for hemoglobin s mthesis or to store iron if an excess is absorbed by the body. 

Recently, this problem has been approached by reverting to reading the color of the bilirubin directly. This used to be called an "Icterus Index", in which the color of the serum was compared to a dilute dichromate solution (39). However, the new approach has been to use two wavelengths. This can be used in either of two different procedures. In one procedure the reading is made at the peak for bilirubin which is at 453 nm and at an isosbestic point for hemoglobin (40). The effect on the reading due to hemoglobin is subtracted from the bilirubin value. Commercial instruments based on this principle have not been successful. 

O Sickle cell disease is an inherited disorder caused by a defect in the gene for hemoglobin. Patients may have one defective gene (sickle cell trait) or two defective genes (sickle cell disease). 

Benesch, R.E., and Kwong, S. (1988) B/s-pyndoxal polyphosphates A new class of specific intramolecular cross-linking agents for hemoglobin. Biochem. Biophys. Res. Comm. 156, 9. 

The qualitative relationship between the oxygen binding curves for hemoglobin and myoglobin. 

Table 3.4 lists values for A Eq and for some important oxidation and spin states found in bioinorganic molecules. Data are taken from reference 24 and from Table 1 of reference 25 for hemoglobin, myoglobin, and the picket-fence porphyrin model compound, FeTpivPP(l-Melm).25 The myoglobin and hemoglobin model compounds are discussed in Section 4.8.2. Reference 26 provides the Table 3.4 data on iron sulfur clusters found in many bioinorganic species.26 The unusual iron-sulfur and iron-molybdenum-sulfur clusters found in the enzyme nitrogenase are discussed more fully below and in Chapter 6. 

Figure 4.12 Distal histidine hydrogen bonding structure for hemoglobin (left) and a heme model (right). (Reprinted with permission from Figure 12 of Momenteau, M. Reed, C. A. Chem. Rev., 1994, 94, 659-698. Copyright 1994, American Chemical Society.)...

Studies investigating the bioavailability of P.Y.17 in rats, applied not only orally but also by inhalation, in no case showed the presence of any cleavage product of the pigment (e.g., 3,3-dichlorobenzidine or metabolites) in the urine or blood of the animals [31]. Similar studies were carried out with P.Y.13 and 174 [32], Recently the non-bioavailability of 3,3 -dichlorobenzidine from P.Y.13 and P.Y.17 was confirmed by means of molecular dosimetry for hemoglobin and DNA adducts [33]. 

To get from the amino acid analysis of the protein to its structure, its molecular weight had to be estimated. As early as 1885 Zinoffsky had reported a minimum molecular weight for hemoglobin of 16.73 kDa based on its elementary composition and assuming one atom of iron/ mole, a remarkably accurate figure. For most proteins because of their large size and ease of denaturation, classical cryoscopic or ebulliscopic methods were impracticable. Osmotic pressure measurements were... 

Owing to the importance of the tetrahedral model for hemoglobin, we present also the form of the correlation functions in the limit T 0. Recall (Section 4.7) that in this limit all the subunits change simultaneously from H to L. Thus, we have a two-state adsorbing system. In this case the intrinsic binding constant is... 

I. A 10-month-old child is being evaluated for the underlying cause of a hemolytic anemia. In the diagram shown below, the oxygen dissociation curve for hemoglobin in his erythrocytes is compared with the curve obtained with normal red cells. 

---