Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemical reactivity of 8-chloroflavins and 8-mercaptoflavins has been exploited in order to examine the orientation of protein-bound flavins relative to solvent. The apoprotein form of a series of flavoproteins was prepared and the native flavin was replaced by either 8-Cl-flavin or 8-mercaptoflavin (FAD, FMN, or riboflavin form as was appropriate). The reconstituted proteins were exposed to reagents capable of reacting with the group at position 8. The 8-Cl-proteins were challenged with sodium sulfide and thiophenol, while the 8-mercaptoproteins were faced with iodoacetamide and iodoacetic acid. The kinetics of the ensuing reactions served as a measure of the solvent availability of position 8 for the protein-bound flavin. These studies indicated that position 8 of flavin bound to melilotate hydroxylase, D-amino acid oxidase, old yellow enzyme, p-OH-benzoate hydroxylase, and flavodoxin is accessible to solvent, while position 8 on L-lactate oxidase, glucose oxidase, putrescine oxidase, and riboflavin-binding protein appears to be inaccessible. For luciferase, D-lactate dehydrogenase, and xanthine oxidase, the data suggest that position 8 is exposed but the results are inconclusive. The effect of ligand binding on the accessibility of position 8 was also studied. NADPH binding to 8-mercapto old yellow enzyme and benzoate binding to 8-Cl-D-amino acid oxidase results in complete blockage of previously available position 8. On the other hand, p-OH-benzoate hydroxylase and melilotate hydroxylase bind their respective substrates (p-OH-benzoate and melilotate) without significantly altering the reactivity of position 8.
 ...
PMID:Active site probes of flavoproteins. Determination of the solvent accessibility of the flavin position 8 for a series of flavoproteins. 689 55

Sodium-hydrogen exchange (NHE) represents an important process mediating myocardial ischemic and reperfusion injury, and NHE inhibitors have been shown to be effective cardioprotective agents against this form of injury. The precise mechanisms by which NHE inhibition protect the heart are not known and we therefore postulated that attenuation of oxidative stress could contribute to such protection. Accordingly, we examined whether the potent and specific NHE inhibitor 4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate (HOE 642, 5 microM) can protect isolated rat hearts against mechanical and biochemical impairment produced by either hydrogen peroxide (150 or 200 microM) or a free radical generating system consisting of purine (4.6 or 9.2 mM) and xanthine oxidase (20 or 40 U/L). HOE 642 significantly delayed and attenuated both the depression in left ventricular developed pressure (LVDP) as well as the elevation in left ventricular end-diastolic pressure (LVEDP) produced by both concentrations of hydrogen peroxide, although greater protection was generally seen against the lower hydrogen peroxide concentration, particularly with respect to LVEDP. Hydrogen peroxide, at both concentrations, significantly reduced high energy phosphate and glycogen contents and elevated lactate levels, all of which were significantly attenuated by HOE 642. In contrast, HOE 642 had no effect on functional impairment produced by either concentration of the free radical generating system. At its lower concentration, the combination of purine plus xanthine oxidase had no effect on energy metabolites, although a significant reduction in high energy phosphate stores was seen with the higher concentration. However, this was unaffected by HOE 642. The protective effect of HOE 642 was mimicked by another NHE inhibitor, methylisobutylamiloride (MIA, 5 microM). Our study therefore shows that NHE inhibition selectively protects against functional and metabolic impairment produced by hydrogen peroxide. Since hydrogen peroxide formation has been implicated in the development of ischemic and reperfusion injury, it is possible that the protective effect of NHE inhibition against this form of oxidative stress may explain in part the basis for the well-established salutary actions of NHE inhibitors in the ischemic and reperfused myocardium. Since HOE 642 failed to modify the response to free radical generators, it is unlikely that the protective effects of NHE inhibitors can be explained by a free radical scavenging mechanism.
 ...
PMID:Effect of sodium-hydrogen exchange inhibition on functional and metabolic impairment produced by oxidative stress in the isolated rat heart. 919 59

Loss of adenosine-5'-triphosphate (ATP) and accumulation of inosine-5'-monophosphate (IMP) are the major purine metabolic changes in the skeletal muscle during hypoxia. This study addressed whether chemical metabolic inhibition reflects those changes in cultured skeletal myotube. For this aim, mouse-derived C2C12 myotubes were cultured in Hank's balanced saline solution containing 2 mM sodium cyanide (CN) and/or 1 mM iodoacetic acid (IAA) up to 180 min. Inhibition of oxidative phosphorylation by CN induced a minimal change in the intracellular adenine nucleotide levels during 180 min. Blockage of glycolysis with IAA caused an over 90% decrease in adenine nucleotides both in the cytoplasmic and intramitochondrial spaces, accompanied with allantoin release. Since 1 mM allopurinol entirely inhibited the allantoin generation, xanthine dehydrogenase/oxidase was found to play a key role in the purine catabolism in IAA-treated C2C12 myotubes. By the combined treatment with CN+IAA, ATP exhaustion and IMP accumulation was achieved with significant cell injury. These changes were comparable with those in skeletal muscles during hypoxia, indicating that our model with CN+IAA is well applicable to the investigation of hypoxia-induced myopathy.
 ...
PMID:Catabolism of cytoplasmic and intramitochondrial adenine nucleotides in C2C12 skeletal myotube under chemical hypoxia. 1201 80