Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children undergoing general anesthesia are at increased risk of severe aspiration pneumonitis. Cimetidine and ranitidine, specific histamine (H2-receptor) antagonists, when given 1-3 h preoperatively markedly reduce the acidity and volume of gastric content. A newer compound, famotidine, is a more specific antagonist with no inhibitory effect on the drug metabolizing microsomal enzyme systems of the liver (cytochrome P-450), in contrast to cimetidine. An additional clinical advantage is a possible longer duration of action. In order to evaluate these potential advantages we studied the effects of preanesthetic oral famotidine on gastric fluid pH and volume in 4 groups in a random manner. METHODS. With parental consent, 107 infants and children (ASA I status, 4 months to 14 years old, NPO for at least 6 h) received either no famotidine (n = 29) or 0.15 mg/kg (n = 27), 0.3 mg/kg (n = 25) or 0.6 mg/kg (n = 26) famotidine at 7.00 a.m. Following induction by mask with nitrous oxide/oxygen (N2O/O2) and enflurane (E) or i.v. thiopental, intubation was performed in all patients. Anesthesia was maintained with N2O/O2 and E. A orogastric double-lumen tube was passed into the stomach, and the gastric content was aspirated in a uniform manner. Gastric volume was recorded and pH values were measured with pH paper. RESULTS. In the control group, 28 of 29 patients (97%) had a pH less than 2.5, 18/29 (62%) had a gastric volume greater than 0.4 ml/kg and 17/29 (59%) had a pH less than 2.5 and gastric volume greater than 0.4 ml/kg, meaning an increased risk of pneumonitis if the child aspirates the gastric content. Famotidine administration was effective between 1.5 and 6 h after oral administration. Preoperative famotidine application produces pH values of gastric contents higher than 2.5 in all dosage groups (84%, 94%, 75%), and these differences were highly significant (P less than 0.001), whereas the gastric volume reduction with these doses was not significant. The incidence of pH less than 2.5 and volume of gastric contents exceeding 0.4 ml/kg did not vary with the different doses of famotidine. As there were no measurable differences in the effect of famotidine, we recommend that children at high risk of pulmonary aspiration receive 0.15 mg/kg famotidine orally at least 1.5 h but not later than 6 h before induction.
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PMID:[Famotidine dosage in children. The effect of different doses on the pH and volume of the gastric juice]. 228 7

Regulation mechanisms of the cytochrome P-450 dependent monooxygenase from the hepatic endoplasmic reticulum at 3 different integrational levels are discussed. At the molecular level the activity of the system is regulated by a substrate dependent shift of an equilibrium of cytochrome P-450 spin conformers in favour of the high spin component. A correlation between the extent of the spin shift, the reduction rate and the substrate turnover has been evidenced. The regulation at the membrane level is based on interactions between the 3 essential components of the system: cytochrome P-450, reductase and lipid. The formation of the cytochrome P-450-reductase-complex necessary for oxygen activation by transfer of electrons is dependent on the charge of the phospholipids. The binding constant of the donor-acceptor complex increases with the acidity of the phospholipid head group, thus enhancing the velocity of the electron transfer.
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PMID:[Regulation mechanisms of the endoplasmic cytochrome P-450 systems of the liver]. 389 Aug 47

The binding of thiol, thiolate, thioether, and disulfide sulfur donor ligands to ferric cytochrome P-450-CAM and myoglobin has been investigated by UV-visible absorption, magnetic circular dichroism (MCD), and EPR spectroscopy. For ferric P-450, the binding of all sulfur donors is competitive with substrate binding. Addition of thiols to P-450 leads to interconvertible thiol or thiolate-bound species depending on the thiol acidity (pKa) and the solution ph; ligation of thiols lowers their pKa by about 4 units. In contrast, only the thiolate-bound form is seen for myoglobin regardless of thiol acidity or solution pH (5.5-11.0), indicating that the heme iron of myoglobin is less electron-rich than that of P-450. Thiolate ligands show much higher affinity (Kd approximately 10(-6) M) for ferric P-450 than do thiols (Kd approximately 10(-3) M). The affinity of thioethers for P-450 (Kd approximately 10(-3) M) is pH-independent (pH 5.5-9.0). The observed disulfide coordination to P-450 represents the first example of disulfide ligation to heme iron; no significant evidence for thioether or disulfide binding to myoglobin is seen. Except for the thiolate complexes, the UV-visible and MCD spectral properties of the other sulfur donor . P-450 complexes are similar to, although distinguishable from, those of native P-450. The ferric P-450 . thiolate complexes exhibit MCD spectra resembling that of ferrous P-450 . CO; both also exhibit unique hyperporphyrin (split Soret) UV-visible spectra. The EPR spectra of all P-450 complexes examined display very narrow spread g-values such as are characteristic of native P-450, indicating that the endogenous cysteinate axial ligand is retained upon complex formation. The dissimilarities observed between P-450 and myoglobin in their reactivity toward sulfur donor ligands at least partly reflect the variation in heme iron electron density resulting from their different endogenous axial ligands and may, in turn, help to explain their respective physiological functions of oxygen activation and reversible oxygen binding.
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PMID:Sulfur donor ligand binding to ferric cytochrome P-450-CAM and myoglobin. Ultraviolet-visible absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopic investigation of the complexes. 628 78

In spite of numerous spectroscopic similarities between chloroperoxidase and cytochrome P-450 (P-450) which suggest endogenous cysteinate axial ligation in chloroperoxidase as has been established for P-450, assignment of the endogenous axial ligand of chloroperoxidase has remained controversial since no available free sulfhydryl groups have been detected in chemical studies of chloroperoxidase. To help clarify this problem, we have carried out extensive studies of thiol-binding properties of native ferric chloroperoxidase and have compared our new results with those previously obtained in our laboratory on thiol adducts of P-450. We have found that the ligation of exogenous thiols to the heme iron of chloroperoxidase generates hyperporphyrin (split Soret) spectra (lambda max = approximately 372 and approximately 455 nm), consistent with the formation of bisthiolate low-spin ferric heme adducts as has been established for P-450 and its heme models. However, in contrast to the results with P-450, thiols not only coordinate to the ferric heme iron of chloroperoxidase in the thiolate form in competition with cyanide but also bind, presumably in the thiol form, to a site in the heme vicinity other than the heme iron without competition with cyanide. The thiol acidity (pK alpha greater than 7) or medium pH (pH 3-7) have little effect on the spectral and equilibrium properties of the adducts. Thiol binding to the latter site, which is presumably the organic substrate-binding site, causes a red shift of the Soret peak (339 vector approximately 420 nm) of the high-spin ferric enzyme; the resulting thiol adducts are still predominantly high spin. Similar spectral changes are also observed upon binding of other neutral sulfur (sulfides and disulfide) and oxygen (alcohols and ketones) donor ligands to native ferric chloroperoxidase. In conclusion, the generation of hyperporphyrin spectra upon exogenous thiol binding to native ferric chloroperoxidase provides considerable support for the presence of an endogenous thiolate ligand to the heme of the enzyme in its ferric state.
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PMID:The generation of a hyperporphyrin spectrum upon thiol binding to ferric chloroperoxidase. Further evidence of endogenous thiolate ligation to the ferric enzyme. 654 51