Membrane-bound enzymes cytochrome

Faber stages 52/53, 57/58, and 61/62 (Kistler and Weber, 1974). Since tail muscle regresses during metamorphosis in response to thyroxine, the larvae were reared in thiourea in order to inactivate the thyroid glands. Such treatment presumably has no effect on the level of enzymic activity. As was also noted in the case of liver mitochondria, during the same period of development, the specific activities of the membrane-bound enzymes, cytochrome a - - as and succinate dehydrogenase, remain... 

Plasma levels of 3—5 p.g/mL are obtained two hours after adraiinistration of 200 mg ketoconazole. No accumulation in the bloodstream was noted after a 30-wk treatment with this dose. The half-life is approximately eight hours. When ketoconazole is taken with meals, higher plasma levels are obtained. Distribution studies using radioactive ketoconazole in rats show radioactivity mainly in the Hver and the connective tissue. Radioactivity is also present in the subcutaneous tissue and the sebaceous glands. After one dose of 200 mg in humans, ketoconazole is found in urine, saUva, sebum, and cenimen. Like miconazole, the mode of action is based on inhibition of the cytochrome P-450 dependent biosynthesis of ergosterol. This results in disturbed membrane permeabiUty and membrane-bound enzymes (8,10,23,25). 

This cytochrome oxidase ( o is an abbreviation for oxidase) is widely distributed and may completely or partly replace cytochrome oxidase aa3 under conditions where the supply of dioxygen is limited. It is a membrane-bound enzyme which has proved difficult to purify, and whose spectral characteristics are those of b cytochromes. Its identity is usually confirmed by observation of the distinctive spectral features of its complex with carbon monoxide. 

Fatty acyl-CoA desaturases are terminal oxidases of a membrane-bound enzyme complex that also includes cytochrome b5 and cytochrome b5 reductase (Bloomfield and Bloch, 1960). They remove substrate hydrogen atoms at a position determined by the specificity of the enzyme. They play essential roles in regulating membrane fluidity and are also involved in insect lipid and pheromone metabolism. They share the presence of three highly conserved histidine-rich sequences (H-boxes) that coordinate the diiron-oxo structure at the active sites (Shanklin and Cahoon, 1998) and four hydrophobic a helices that appear to anchor the protein into the lipid bilayer and situate the H-boxes in their correct position in the active site. 

In the terminal reaction of the respiratory chain, membrane-bound cytochrome c oxidase (CcO) receives electrons from soluble cytochrome c and passes them on to 02. CcO is a multisubunit membrane-bound enzyme with four redox cofactors (Cua, cytochrome a, cytochrome 03, Cub). The... 

This reaction is catalyzed by a complex of three membrane-bound enzymes NADH-cytochrome h reductase, cytochrome b, and a desaturase (Figure 22.29). First, electrons are transferred from NADH to the FAD moiety of NADH-cytochrome b 5 reductase. 

The first illustration of this class of enzymes is the haem-copper cytochrome c oxidase (CcO), the terminal component of the respiratory chain in aerobic organism. These membrane-bound enzymes catalyse the reduction of molecular dioxygen to water (Reaction (4)) at the rate of up to 250 molecules of O2 per second ... 

Other membrane-bound enzymes are known to catalyze oxygen transfer. Among them, cytochrome-P450-dependent monooxygenases catalyze a large number of reaction including the epoxidation of alkenes by molecular oxygen... 

These nitrite reductases are described as monomers of about 60 kDa, containing six c-type hemes, five being low-spin and one high-spin in the as-isolated state [134]. However, recent evidence has indicated that the situation maybe more complex. In E. coli, the gene for the nitrite reductase (nrfA) codes for a 50 kDa cytochrome containing four (or five), rather than six heme-binding sites [135]. The membrane-bound enzymes were shown not to be monomers,... 

Optimal activity of the purified enzyme solubilized in Triton X-100 is obtained in the presence of excess phospholipids. The pH optimum of the steady-state reaction with horse heart ferrocytochrome c occurs at pH 6, yielding a turnover of about 80 electrons/sec, similar to the value obtained for the enzyme from P. denitrificans. Remarkably, a purified membrane-bound c cytochrome, identified by its N-terminal sequence as cytochrome Ci from the 6c 1 complex, stimulates the rate of electron transfer between horse heart c5d ochrome c and the cytochrome c oxidase by about a factor of two. The in vitro enzyme assay with purified cytochrome oxidase and reduced amicyanin showed no activity only after the addition of endogenous cytochrome C550 (or horse heart cjfto-chrome c) did oxidation of amicyanin occur, in agreement with the sequence of electron transfer ami — cjft C550 CCO. 

Presently, three enzyme systems have been identified as being capable of metabolizing organic nitrates, namely, a cytochrome P-450 (CYP) enzyme, a glutathione-S-transferase (GST), and a membrane-bound enzyme that has yet to be named. A recent review has addressed this topic (Bennett et al., 1994). Here, we examine the evidence, for and against, implicating each of these enzymes as the pharmacologically pertinent system. 

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