FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1973454777> ?p ?o ?g. }

• W1973454777 endingPage "19" @default.
• W1973454777 startingPage "8" @default.
• W1973454777 abstract "Generation of unbound nitric oxide (NO) via the oxidative denitrosylation (ODN) mechanism is proposed to involve the simultaneous reaction of nitrite with oxy and deoxy hemoglobin (Hb(O2) (k1) and Hb (k13)) to yield respectively, NO2 and Hb+ 2(NO). These two reaction pathways are coupled when NO2 reacts with Hb+ 2(NO) to yield Hb+ 3(NO) (k22), a species that releases NO rapidly. Here, I have constructed an experimentally based molecular model of the ODN mechanism (k1–k31), focusing on the high nitrite reductase activity of R-state hemoglobin. This model was used to test the hypothesis that human fetal hemoglobin (HbF) can generate unbound NO faster and to a greater extent than HbA, consequent to a 25-fold larger value of k1, which was determined in an earlier study. The results show that despite the use of identical values for k22, there was a 44-fold larger apparent rate of reaction of NO2 with HbF(NO) compared to HbA(NO), for reactions simulated at 410 μM nitrite and 100 μM hemoglobin (heme basis), 50% oxygen saturation at pH 7.4 and 37 °C. This faster reaction was associated with the generation of about 11 μM peak unbound NO. In contrast, HbA failed to generate unbound NO rapidly under the same conditions. However, raising the concentration of nitrite into the millimolar range did generate unbound NO in the HbA simulation, in agreement with the experimental literature, and that result was associated with acceleration in the rate of reaction of NO2 with HbA(NO). Unbound NO could be generated at 410 μM nitrite in the HbA simulation by lowering the pH. This too was associated with an acceleration in the rate of reaction of NO2 with HbA(NO). Furthermore, generation of unbound NO could be assigned to the pH-dependent increase in k1, independent of the associated increase in k13. Finally, selective exchange of the HbA value of k1 for the HbF value, keeping all other constants and conditions unchanged, generated kinetic patterns for the various species of the “k1-modified” HbA simulation, which were virtually indistinguishable from those seen in the HbF simulation. Taken together, these findings show that rapid and extensive generation of unbound NO within the ODN mechanism is controlled by the value of k1. The faster and more extensive generation of unbound NO by HbF at micromolar nitrite concentration suggests a possible second function for HbF in sickle cell disease, namely enhanced vasodilation. The failure of 410 μM nitrite to generate unbound NO in the HbA simulation at pH 7.4, contrasts with evidence in the literature showing that exposure of intact red cells to 100 to 200 μM nitrite in PBS, promoted NO release into the gas phase. I point out that this difference in outcome may be due to the higher activity of HbA when bound to the cytoplasmic domain of the red cell membrane anion transport protein SLC4A1 (band 3) and to the demonstrated capacity of band 3 to transport nitrite." @default.
• W1973454777 created "2016-06-24" @default.
• W1973454777 creator A5059293761 @default.
• W1973454777 date "2013-01-01" @default.
• W1973454777 modified "2023-10-05" @default.
• W1973454777 title "The oxidative denitrosylation mechanism and nitric oxide release from human fetal and adult hemoglobin, an experimentally based model simulation study" @default.
• W1973454777 cites W1510510119 @default.
• W1973454777 cites W1521597094 @default.
• W1973454777 cites W1545912435 @default.
• W1973454777 cites W1557041579 @default.
• W1973454777 cites W1589586351 @default.
• W1973454777 cites W1975418664 @default.
• W1973454777 cites W1977243529 @default.
• W1973454777 cites W1989938700 @default.
• W1973454777 cites W1998093640 @default.
• W1973454777 cites W2002449990 @default.
• W1973454777 cites W2008061810 @default.
• W1973454777 cites W2014802266 @default.
• W1973454777 cites W2016000926 @default.
• W1973454777 cites W2033357754 @default.
• W1973454777 cites W2057813936 @default.
• W1973454777 cites W2058713290 @default.
• W1973454777 cites W2067236368 @default.
• W1973454777 cites W2070845549 @default.
• W1973454777 cites W2077180688 @default.
• W1973454777 cites W2095115132 @default.
• W1973454777 cites W2111085674 @default.
• W1973454777 cites W2118089880 @default.
• W1973454777 cites W2120714892 @default.
• W1973454777 cites W2149709371 @default.
• W1973454777 cites W2152287206 @default.
• W1973454777 cites W2158139687 @default.
• W1973454777 cites W2170607667 @default.
• W1973454777 cites W2413071776 @default.
• W1973454777 cites W2026480555 @default.
• W1973454777 doi "https://doi.org/10.1016/j.bcmd.2012.08.006" @default.
• W1973454777 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22981699" @default.
• W1973454777 hasPublicationYear "2013" @default.
• W1973454777 type Work @default.
• W1973454777 sameAs 1973454777 @default.
• W1973454777 citedByCount "17" @default.
• W1973454777 countsByYear W19734547772014 @default.
• W1973454777 countsByYear W19734547772015 @default.
• W1973454777 countsByYear W19734547772018 @default.
• W1973454777 countsByYear W19734547772019 @default.
• W1973454777 countsByYear W19734547772020 @default.
• W1973454777 countsByYear W19734547772021 @default.
• W1973454777 countsByYear W19734547772022 @default.
• W1973454777 countsByYear W19734547772023 @default.
• W1973454777 crossrefType "journal-article" @default.
• W1973454777 hasAuthorship W1973454777A5059293761 @default.
• W1973454777 hasConcept C12554922 @default.
• W1973454777 hasConcept C134121241 @default.
• W1973454777 hasConcept C172680121 @default.
• W1973454777 hasConcept C178790620 @default.
• W1973454777 hasConcept C181199279 @default.
• W1973454777 hasConcept C185592680 @default.
• W1973454777 hasConcept C191897082 @default.
• W1973454777 hasConcept C192562407 @default.
• W1973454777 hasConcept C2776179834 @default.
• W1973454777 hasConcept C2776217839 @default.
• W1973454777 hasConcept C2776317666 @default.
• W1973454777 hasConcept C2776384668 @default.
• W1973454777 hasConcept C2778917026 @default.
• W1973454777 hasConcept C2779234561 @default.
• W1973454777 hasConcept C2781341435 @default.
• W1973454777 hasConcept C2910876585 @default.
• W1973454777 hasConcept C519581460 @default.
• W1973454777 hasConcept C540031477 @default.
• W1973454777 hasConcept C54355233 @default.
• W1973454777 hasConcept C55493867 @default.
• W1973454777 hasConcept C57600042 @default.
• W1973454777 hasConcept C86803240 @default.
• W1973454777 hasConceptScore W1973454777C12554922 @default.
• W1973454777 hasConceptScore W1973454777C134121241 @default.
• W1973454777 hasConceptScore W1973454777C172680121 @default.
• W1973454777 hasConceptScore W1973454777C178790620 @default.
• W1973454777 hasConceptScore W1973454777C181199279 @default.
• W1973454777 hasConceptScore W1973454777C185592680 @default.
• W1973454777 hasConceptScore W1973454777C191897082 @default.
• W1973454777 hasConceptScore W1973454777C192562407 @default.
• W1973454777 hasConceptScore W1973454777C2776179834 @default.
• W1973454777 hasConceptScore W1973454777C2776217839 @default.
• W1973454777 hasConceptScore W1973454777C2776317666 @default.
• W1973454777 hasConceptScore W1973454777C2776384668 @default.
• W1973454777 hasConceptScore W1973454777C2778917026 @default.
• W1973454777 hasConceptScore W1973454777C2779234561 @default.
• W1973454777 hasConceptScore W1973454777C2781341435 @default.
• W1973454777 hasConceptScore W1973454777C2910876585 @default.
• W1973454777 hasConceptScore W1973454777C519581460 @default.
• W1973454777 hasConceptScore W1973454777C540031477 @default.
• W1973454777 hasConceptScore W1973454777C54355233 @default.
• W1973454777 hasConceptScore W1973454777C55493867 @default.
• W1973454777 hasConceptScore W1973454777C57600042 @default.
• W1973454777 hasConceptScore W1973454777C86803240 @default.
• W1973454777 hasIssue "1" @default.
• W1973454777 hasLocation W19734547771 @default.
• W1973454777 hasLocation W19734547772 @default.

• next