Ferrous protoporphyrin

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

Heme When the two hydrogens on the center nitrogens in protoporphyrin are replaced by one iron atom the resulting compound is heme, also known as ferrous protoporphyrin j (see Fig. 4 on page 5). The iron is coordinated to the four pyrrole nitrogens, the entire structure being approximately planar. Two other coordination positions, labelled 5 and 6, are available in directions perpendicular to the heme plane (Fig. 4 b). In heme the iron atom is in the divalent or ferrous (Fe2+) state. 

The final step in heme synthesis involves the incorporation of ferrous iron into protoporphyrin in a reaction catalyzed by ferrochelatase (heme synthase), another mitochondrial enzyme (Figure 32-4). 

In tracing the evolutionary development of iron ligands it is of interest to examine the machinery employed by organisms which carry out reactions on those substances believed to have been present on the primitive Earth. Specific substrates acted on by this group include, besides ferrous iron itself, hydrogen sulfide, hydrogen gas, methane and reduced nitrogen compounds. Species which perform photosynthesis may be presumed to have the capacity to synthesize protoporphyrin IX since this substance is an intermediate in chlorophyll biosynthesis (43). 

The main metalloporphyrin in the body is heme, which has a ferrous Fe iron atom coordinated by protoporphyrin DC... 

The ferrous complex of octaethyl porphyrin in SDS micelles has been characterized as four coordinated (S = 1) ferrous heme species and is similar to that observed for the ferrous protoheme complex in CTAB. It is noted that ferrous complexes of natural porphyrins cannot be stabilized in aqueous SDS micelles, and much larger aqueous micelles like CTAB were needed to stabilize various ferrous protohemes. This indicates that the environment around the octaethyl porphyrin complex in aqueous SDS is more hydrophobic than that of the analogous natural heme species, suggesting that the OEP moiety is embedded much deeper inside the micellar hydrophobic cavity than the protoporphyrin analogue. 

The NMR of ferrous complexes of MPll and MP8 in aqueous SDS solutions has been studied the spectra are very broad and ill-resolved [23]. The heme proton resonances appear in the range 15 to 30 ppm and resemble those of ferrous hemoproteins. The similarity in the linewidths and spectral range of the heme protons in these ferrous peptide complexes with the ferrous hemoproteins suggests that the larger size of the heme peptide restricts the mobility of the molecule inside the micelles compared to that in case of the protoporphyrin complex in micellar solutions, where the spectrum is better resolved. 

The micelle-encapsulated six coordinated bis(pyridinato) iron(II) complexes of protoporphyrin and OEP have been reported by addition of pyridine to the four coordinate ferrous complex in aqueous micellar solution. The optical spectrum of [Fe(II)(PP)(Py)2] in micelle (Fig. 10) is identical to S = 0 six-coordinate bis(pyridinato) iron(II) porphyrin complex [3]. The magnetic moment measurements in solution confirm their diamagnetic nature. The HNMR spectra are also characteristic low-spin iron(II) resonances (S = 0) with shifts lying in the diamagnetic region (Table 2). 

FIGURE 5-1 Heme. The heme group is present in myoglobin, hemoglobin, and many other proteins, designated heme proteins. Heme consists of a complex organic ring structure, protoporphyrin IX, to which is bound an iron atom in its ferrous (Fe2+) state, (a) Porphyrins, of which protoporphyrin IX is only one example, consist of four pyr-... 

Heme is a complex of protoporphyrin IX and ferrous iron (Fe2+).The iron is held in the center of the heme molecule by bonds to the four nitrogens of the porphyrin ring. The Fe2+ can then form two additional bonds, including one to molecular oxygen. 

The insertion of ferrous iron into the porphyrin ring in the biosynthesis of heme is catalyzed by the enzyme ferrochelatase. A deficiency in ferrochelatase activity results in an accumulation or the excretion of unchelated protoporphyrin in patients with erythrohepatic protoporphyria. Ferrochelatase catalyzes the synthesis of a range of metalloporphyrins,628 and, for example, produces zinc protoporphyrin in erythrocytes of patients with iron-deficiency anaemia. 

The iron atom in haems and haemoproteins is usually five- or six-coordi-ftate, since it can bind ligands at the axial positions. Haems such as tron(II) protoporphyrin IX will readily coordinate neutral bases such as NHj and pyridine, small unsaturated molecules like CO, and some anions. In haemoproteins, at least one of the axial ligands is provided by the polypeptide, and with the exception of some cytochromes, this is the only linkage between the polypeptide and the prosthetic group. Where only We axial position is occupied by the polypeptide, the other is thought to be taken up by a water molecule in ferric haemoproteins. This is readily replaced by other ligands. Ferrous haemoproteins, in the absence of potential ligands such as CO, can remain five-coordinate. 

In the native deoxy form the active site consists of an iron(II) protoporphyrin IX encapsulated in a water resistant pocket and bound to the protein through the imidazole group of the histidine residue F8. The ferrous ion is 5-coordinate which allows the reversible binding of molecular oxygen in the sixth coordination site as shown in Fig. 17-E-7. 

Into mitochondrion having migrated— ing migrated Two vinyls first are formed Ifom propionates—propionates For protoporphyrin IX to be created—be created Coproporphyrinogen de saturates— saturate s Ferrous iron is finally inserted— ly inserted The enzyme now of course ferrochelatase— chelatase So two simple starting substances converted— ces converted To a complex haem which can t fail to amaze ... 

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