Cytochrome hemoproteins

Many drugs when administered to humans can result in a marked increase in ALASl. Most of these drugs are metabolized by a system in the liver that utilizes a specific hemoprotein, cytochrome P450 (see Chapter 53). During their metabolism, the utilization of heme by cytochrome P450 is greatly increased, which in turn diminishes the intracellular heme concentration. This latter event effects a derepression of ALASl with a corresponding increased rate of heme synthesis to meet the needs of the cells. 

It has been clearly established that Pseudomonas putida which has been selected to grow on camphor possesses an oxidative metabolic system (54). It contains a hemoprotein, cytochrome Qrn>... 

The following discussion will center on mixed-function oxidases involving the hemoprotein cytochrome P-450, the active center of which consists of protoporphyrin IX. Mixed-function oxidases based on cytochrome P-450 are perhaps best known for their role in the primary metabolism of lipophilic xenobiotics in mammals, birds, fish and many invertebrates including insects. While this function is often critical in determining the survival of an organism... 

Artacho E, Sanchez-Portal D, Ordejon P, Garcia A, Soler JM (1999) Linear-scaling ab-initio calculations for large and complex systems. Phys Status Solid B 215 809-817 Sato F, Yoshihiro T, Era M, Kashiwagi H (2001) Calculation of all-electron wavefunction of hemoprotein cytochrome c by density functional theory. Chem Phys Lett 341 645-651 Inaba T, Tahara S, Nisikawa N, Kashiwagi H, Sato F (2005) AU-electron density functional calculation on insuhn with quasi-canonical localized orbitals. J Comput Chem 26 987-993... 

This may be a reason for the unique role of sulfur in the hemoprotein cytochrome P450. In order to explain the N-demethylation activity of ferric microsomal cytochrome P450 in the presence of hydrogen peroxide, Ullrich et al. have formulated the following reaction ... 

A fourth complex connects site 1 to site 2. Thus, the first complex in the chain consists of the enzyme NADH dehydrogenase and a group of around five closely linked proteins that contain electron-rich iron-sulphur clusters. These are non-heme proteins vital to the flow of electrons through the chain. The second complex consists of the enzyme succinate dehydrogenase and its collection of iron-sulphur proteins. The third complex contains the hemoproteins cytochromes b and Cj, and one iron-sulphur protein. The final complex, the one that actually reduces oxygen to water, is called cytochrome oxidase and contains two heme groups (heme a and heme a ) and two copper centres. Ubiquinone, also known as coenzyme Q, is a lipid-soluble quinone which connects the first, second, and third complexes. Cytochrome c is the electron carrier hemoprotein that links the complexes of site 2 to cytochrome oxidase in site 3. 

The hemoprotein cytochrome c, located in the intermembrane space, serves a dual role in mitochondrial function [37]. First, it is essential for electron transfer from complex m to cytochrome oxidase (complex IV) during mitochondrial respiration. Second, cytochrome c is one of a number of apoptogenic or apoptosis-inducing factors (AIFs) involved in mitochondria-dependent apoptosis [10,11]. In response to certain proapoptotic stimuli, cytochrome c dissociates... 

Figure 1. Electron transport chains of the endoplasmic reticulum. (A) Microsomal acyl-Co A desaturation system composed of NADH-cytochrome reductase, cytochrome fos (a flavoprotein), and fatty acyl-CoA desaturase. (B) Microsomal hydroxylase system depicting participation of the NADPH-cytochrome P-450 reductase (a flavoprotein), cytochrome P-450, and phosphatidylcholine. The role of the phospholipid appears to be in enhancing interaction of the proteins. The reduced form of the hemoprotein cytochrome P-450, on addition of carbon monoxide, envinces a Soret maximum at 450 nm, accounting for its designation. There is evidence that these two systems (A and B) interact in the membrane.

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