Cytochrome monooxygenases

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

In the endoplasmic reticulum of eukaryotic cells, the oxidation of the terminal carbon of a normal fatty acid—a process termed ch-oxidation—can lead to the synthesis of small amounts of dicarboxylic acids (Figure 24.27). Cytochrome P-450, a monooxygenase enzyme that requires NADPH as a coenzyme and uses O, as a substrate, places a hydroxyl group at the terminal carbon. Subsequent oxidation to a carboxyl group produces a dicarboxylic acid. Either end can form an ester linkage to CoA and be subjected to /3-oxidation, producing a... 

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. 

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

Some of the major enzyme groups that facilitate this transformation are heme-containing MOs of the cytochrome P450 type [111], alkane hydroxylases, xylene monooxygenases, styrene monooxygenases [105], and haloperoxidases [112],... 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

There is increasing evidence that microsomal monooxygenases with cytochrome P450 as their active center have a dominant role in the detoxication of the great... 

Monooxygenases owe their catalytic properties to the hemeprotein cytochrome P450 (Fignre 2.3). Within the membrane of the endoplasmic reticulum (microsomal... 

The microsomal fraction consists mainly of vesicles (microsomes) derived from the endoplasmic reticulum (smooth and rough). It contains cytochrome P450 and NADPH/cytochrome P450 reductase (collectively the microsomal monooxygenase system), carboxylesterases, A-esterases, epoxide hydrolases, glucuronyl transferases, and other enzymes that metabolize xenobiotics. The 105,000 g supernatant contains soluble enzymes such as glutathione-5-trans-ferases, sulfotransferases, and certain esterases. The 11,000 g supernatant contains all of the types of enzyme listed earlier. 

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