Cell hemins

Hemins Cell hemins Electrons Hemins Blood... 

Cytochromes are formally closely related to the chlorophylls. They also possess the porphyrin skeleton which, in their case, complexes iron, not Mg++ (Fig. 29). A whole series of other biologically important substances such as the peroxidases, catalases, and the red blood pigment hemin also contain these same structural components (iron + porphyrin). All of these substances, including the cytochromes, are known collectively as cell hemins. In the living cell the iron-containing porphyrin system is linked to protein. Thus, the cell hemins occur as proteids. 

Phycobiliproteins. The bile pigments of animal organisms are open chain tetrapyrroles. They arise by degradation of cell hemins. This degradation entails opening of the porphyrin ring which thus leads to open chain tetrapyrroles. 

Cytochrome c is the best studied cytochrome, because it is soluble and relatively easily obtained. For its chemical constitution see Chapt. IX-6. It is responsible for the electron transport from flavin (or a quinone) to cytochrome oxidase. It is noteworthy that neither CN nor CO can inhibit cytochrome c. While the soluble cytochrome c has been known for some time now, two closely related cell hemins were discovered recently, a cytochrome c lipoprotein and a cytochrome Ci. 

Iron has already been discussed as a component of hemoglobin and cell hemins, both very important biocatalysts. Thus it is a vital element. The human organism contains 4-5 gm, of which is in hemoglobin. The cytochromes and iron-containing flavoproteins sequester only a small fraction of the total iron. 

Sistonen, L., Sarge, K.D., Phillips, B., Abravaya, K., Morimoto, R.I. (1992). Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells. Mol. Cell. Biol. 12,4104-4111. 

Theodorakis, N.G., Zand, D.J., Kotzbauer, P.T., Williams, G.T., Morimoto, R.I. (1989). Hemin induced transcriptional activation of the hsp70 gene during erythroid maturation in K562 cells is due to a heat shock factor mediated stress response. Mol. Cell. Biol. 9,3166-3173. 

In patients clearance of intravenous heme is rapid until hemopexin levels are depleted (148), and lack of interaction with hemopexin may explain the higher clinical efficacy of heme-arginate compared with hemin itself (149, 150). In intact animals, i.v. heme causes rapid association of hemopexin but not albumin with the liver (47, 63, 68), and heme uptake from heme-albumin complexes into isolated rat hepato-cytes occurs via diffusion of heme released from its loose complex with BSA (137). Moreover, unlike uptake from heme-hemopexin, free heme uptake by cells occurred even at 4°C, as expected for nonspecific membrane association and in total disagreement with a membrane-receptor-mediated or active transport uptake process. 

The CLD methods for HPLC using isoluminol (190) with microperoxidase catalysis, for determination of lipid hydroperoxides in clinical fluids, have been reviewed. Determination of phospholipids hydroperoxides by luminol (124) CL has been reviewed . A fast RP-HPLC method (retention times 1 to 2 min) for determination of hydroperoxides and other peroxide compounds includes UVD, which is not always effective, and CLD, attained on injection of luminol (124), the CL reagent (Scheme 3), hemin (75a), a catalyst, and NaOH to raise the pH of the solution. A FLD cell may act as CLD cell if the excitation source is turned off. The selectivity of CLD is of advantage over UVD in industrial analysis thus, for example, UVD of a sample from a phenol production line based on cumene oxidation (equation 13) shows peaks for cumyl hydroperoxide (27), unreacted cumene, cumyl alcohol and acetophenone, whereas CLD shows only the 27 peak. The... 

A procedure for determination of lipid hydroperoxides in human plasma is based on kinetic measurement of the CL of luminol (124) with hemin (75a) catalysis . CLD of microperoxidase-catalyzed oxidation of luminol (124) or isoluminol (190) was applied to detection and determination of amino acid hydroperoxides after exposure to UV and y-irradiation A method for determination of hydroperoxides in the phospholipids of cultured cells uses isoluminol (190) and microperoxidase as catalyst " . Simultaneous determination of phosphatidylcholine hydroperoxides and cholesteryl ester hydroperoxides in human serum is carried out by quantitative extraction of the lipids, HPLC separation by column switching and CLD using isoluminol (190) with microperoxidase catalysis . ... 

Iron(n) is known to decompose hydrogen and dialkyl peroxides to free radicals by reductive cleavage of the 0—0 bond and early investigations established the parasite s sensitivity to these species. When treated with radiolabelled C-artemisinin, the hemin-hemozoin fraction of the lysed malaria-infected erythrocytes was shown to contain a radiolabel, though the mechanism of incorporation is not clear. Meshnick and coworkers demonstrated that uninfected cells did not contain radiolabelled proteins whereas six radiolabelled proteins were isolated from cells infected with the Plasmodium falciparum (P. falciparum) strain of the parasite. It was suspected that one of the alkylated proteins was the Histidine Rich Protein (HRP) that was known to bind multiple heme monomers and therefore thought to be instrumental to the parasite s detoxification process. Moreover, iron chelators were found to inhibit the lethal effects of peroxides on the parasite. ... 

Proteins with molecular weights in the millions are the major constituents of all living cells. Simple proteins are hydrolyzed only to amino acids. Coqjugated proteins are hydrolyzed to amino acids and nonpeptide substances known as prosthetic groups. These prosthetic groups include nucleic acids of nucieoproteins, carbohydrates of glycoproteins, pigments (such as hemin and chiorophyli) of chromoproteins, and fats or lipids of lipoproteins. 

Committed step in heme synthesis, its coenzyme, and inhibitor The committed step in heme synthesis is the formation of 5-amlnolevulinic acid (ALA). The reaction, which requires pyridoxal phosphate as a coenzyme, is catalyzed by ALA synthase. The reaction is inhibited by hemin (the oxidized form of heme that accumulates in the cell when it is being under-used). The conversion of protoporphyrin IX to heme, catalyzed by ferrochelatase, is inhibited by lead. 

Jarolim, P., Lahav, M., Liu, S. C., and Palek, J. (1990). Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins Correlation with a release of hemin. Blood 76, 2125-2131. 

Figure 5.8 Detection of PNA-induced 7-globin gene expression in K562 cells with RNase Protection Assay. Lane 1, K562 cells lane 2 to lane 4, K562 cells treated with PNAs for two, three, and four days, respectively lane 5, K562 cells treated with hemin (75 pM) for three days.

The q2 value of a CoMFA model, together with other statistical information from the pis analysis, provides information on the predictive capability of the model. In this study we have generated CoMFA models that describe the pharmacophore either with or without the involvement of hemin, both of which provide good q2 values. Selection of the model that most accurately depicts reality is not trivial since many variables are inherent in the cell-culture bioassay results. However, it may be... 

Note that the monooxygenase model reactions described above are performed in non-aqueous diluters. Therefore, hematin form is absent and only hemin is present, of which, apparently, formation of an intermediate shaped as Hm=0 is typical. Model catalysts of cytochrome P-450 operate in liquids, similar to enzymes themselves. Their activity depends on many factors, including diluter origin, reaction mixture pH and cell effects. As indicated [1], the gas-phase version of the oxidation process is much freer from these effects. 

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