Aggregation of heme

Table 3. Comparison of Heme Aggregation Efficacy of Selected Porphyrins and Metalloporphyrins.

Using Mossbauer spectroscopy to monitor the formation of p-hematin under in vitro reaction conditions, Adams et al. have demonstrated that the reaction is a psuedo-zero-order process [109]. Such a process is consistent with a mechanism whereby a small concentration of heme is kept soluble via acetate, functioning as a phase-transfer catalyst, in a heme-saturated solution. In the rate limiting step, the soluble heme aggregates to P-hematin, which in turn grows until it precipitates from solution. There are clearly complicated heterogeneous reaction equilibria involved in the aqueous chemical formation of p-hematin. Consequently, it should be emphasized that the detailed mechanistic analysis of the complex solubilization of the species involved in the chemical synthesis... 

This work is also notable in that Cole et al. performed detailed aggregation studies of the heme MPPIX using UV-vis and fluorescence spectroscopies to detect the formation of 71-71 hetero-metalloporphyrin assemblies under assay conditions. By employing UV-vis absorbance spectroscopy, the aggregation of porphyrin and metalloporphyrin systems may be examined. The in vitro assay system used for hemozoin... 

For over 300 years, the quinoline family of drugs, and chloroquine in particular, has been used as the primary treatment for malaria. Recent studies have demonstrated that this drug inhibits the aggregation of free heme into hemozoin, allowing levels of monomeric heme to rise until cell lysis occurs. Although the determined structure of hemozoin makes the polymer termination scheme proposed by Sullivan et al. unlikely, hemozoin drug heme interactions appear critical in the inhibition mechanism. Thus, researchers have identified the characteristics of... 

Further investigations of heme peptides from cytochrome c were carried out by both ORD and CD measurements (227, 163, 228, 202). The aggregated hemepeptides were considered as model systems for interactions between hemes in biological systems. By analysis of light-absorption and CD data, exciton interactions between the Soret transitions in aggregated hemes were estimated. Under the conditions used,... 

Cytochrome / can be isolated in a particle of molecular weight 103,000 containing two molecules of be, one of /, nonheme iron, and lipid (299)— in many ways similar to mitochondrial Complex III. This particle cannot be dissociated further without destroying the be and producing aggregation of 34,000 molecular weight monomers of /. Purified cytochrome f apparently exists as an octamer in solution (298). This octamer is the size of the solubilized particles reported earlier by Forti and co-workers (278), but has twice the heme content. 

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