Porphyrin in haemoglobin

The above account of selectivity of inorganic plus organic chemistry in synthesis is given rather extensively to stress three points. All the four (Mg, Fe, Co and Ni) porphyrin products came from one source, the synthesis of uroporphyrin. The basis of selection is very different from that in primitive centres which use thermodynamic stability constant selectivity based on different donor atoms for different metal ions. Here, all ion complexes have the same donor atoms, nitrogen, the most constrained being the coordination of Mg2+ by five nitrogens exactly as is seen for Fe in haemoglobin. Hence, there also has to be a new control feedback to ensure that the appropriate quantities of each metal cofactor is produced in a balanced way, that is synthesis from uroporphyrin has to be divided based upon... 

Related behaviour to that just described occurs in haemoglobin, although the latter is a tetramer consisting of four subunits each containing an iron porphyrin. The latter are located within hydrophobic pockets in the globin portion of the molecule (which, in this case, is composed of four linked chains - consisting of two a and two / chains, which differ in their respective amino acid compositions). 

These are rarely found free but occur as a common prosthetic group of proteins. The first such protein to be extensively studied was the iron porphyrin (Greek porphyra, purple) haemoglobin. This and other iron-porphyrin proteins play a vital role in the physiological activity of nearly all forms of life.146 These forms have the same basic structure (39) but differ in the nature of the pyrrole substituents these are shown for the major porphyrins in Table 13. It has become common practice to refer to all the iron-porphyrin proteins as haem proteins. The function of haemoglobin is, of... 

The porphyrin motif, four pyrrole rings linked by carbon atoms to give a planar cyclic compound, is found in many biomolecules. It is present in haemoglobin and myoglobin and its derivatives are also at the core of vitamin B12, hydrogenases, cytochrome c, the chlorophyll photosystem and similar essential proteins. 

The replacement of native haem with metal-substituted porphyrin can be performed in two ways. In the first, iron ions are removed from the protein by treating native protein with anhydrous HF, followed by insertion of the appropriate metal to metal-free protein [57-59]. In the second, haem is removed either chemically or by recombination (preparing a proper recombinant protein), and then protein is reconstituted with metal-substituted porphyrins [60-64]. The Zn-substituted metal-loproteins such as cytochrome c [65-67], myoglobin [59,61, 62, 64, 68, 69], and haemoglobin [64, 68,70] have been extensively used to study photoinduced ET (PET) between modified proteins and their physiological redox partners. Interestingly, in haemoglobin with a and /3 subunits it was possible to determine ET parameters for... 

Iron prefers to be octahedral with six bonds around it and in one of these spare places in haemoglobin that is occupied by oxygen. If you try and make an oxygen complex of the simple porphyrin with four phenyl groups around the edge yon get a sandwich dimer that oxidizes itself. 

The porphyrin in blood avoids this problem by having another heterocycle to hand. Haemoglobin consists of the flat porphyrin bound to a protein by coordination between an imidazole in the protein (a histidine residue see Chapter 49) and the iron atom. This leaves one face free to bind oxygen and makes the molecule far too big to dimerize. 

Transport Haemoglobin, myoglobin, haemerythrin, haemocyanin Transport only Aerobic heterotrophs Fe (-porphyrins in animals, fungi), Cu (molluscs, arthropods) Co... 

Fig. 3. Diagrammatic sketch showing the change in tertiary structure of a hemoglobin a chain on reaction with oxygen. Movement of the iron atom into the plane of the porphyrin ring causes a movement of helix F toward helix H, which expels tyrosine in position 140 from its pocket between the two helices. From (PIO), M. F. Perutz, Stereochemistry of cooperative effects in haemoglobin. Nature (London) 228, 726 (1970) with permission of the author and publisher.

The IR spectrum of Feni(TPP)(0N02)N0 at low-temperatures has vFe-NO at 548 cm-1 284 The resonance Raman spectrum of NO-bound ferric derivatives of wild-type and mutated (BIO Tyr - Phe) FIbN (a haemoglobin from Mycobacterium tuberculosis) showed vFe-NO and 8Fe-N-0 at 591, 579 cm-1 respectively.285 Nuclear resonance vibrational spectroscopy has been used to identify a number of modes involving motion of iron in the plane of the porphyrin in nitrosyl porphyrins, e.g. Fe NO torsion modes at 27 and 54 cm 1 in Fe(TPP)NO 286... 

These enzymes are able to accept an alectron and then pass it on to another cytochrome. The iron atom is bound, within the haem a, b, c, d group, to a porphyrin coenzyme identical with that found in haemoglobin, with the difference that in the cytochromes the iron undergoes oxidation and reduction. 

Pyrroles (10) can be made the same way, the cyclisation being carried out with ammonia, but an alternative strategy is particularly valuable for carbonyl-substituted pyrroles. Pyrrole esters such as (15) are needed for the synthesis of porphyrins (as in haemoglobin), chlorins (as in chlorophyll), and corrins (vitamin B 2). Ester (IS) has the haem side chain and can be converted by hydrolysis and decarboxylation into a pyrrole (16) with a reactive free position (H in 16). 

The iron in haemoglobin, the protein which carries oxygen in the blood, is bound in the centre of a planar porphyrin structure, referred to as protoporphyrin IX (Fig. 13.1). The compound of this porphyrin with iron is called haeme (ferroprotoporphyrin IX), and in the haemoglobin this unit is attached to the protein by the nitrogen of a histidine unit below the plane of... 

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