Kinetic and cooperative mechanisms of ligand binding to hemoglobin.

Reisberg, P I; Olson, John S.

doi:10.1016/s0021-9258(19)85647-8

Cited by 33 publications

(18 citation statements)

References 26 publications

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“…(5) Hb4 + Me V, 7.7 X 104 M'1 s'1 (6) Hb4(Me)3 + Me if 1 X 106 M'1 s'1 " For the reactions of methyl isocyanide, values in square brackets are for Hb A as reported by Reisberg and Olson (1980b). For CO dissociation reaction, values in square brackets were obtained by nonlinear least-squares fit to eq 2.…”

Section: Data Treatmentmentioning

confidence: 99%

“…The reaction time course of the deoxyHb with isocyanides is complex and subject to varying interpretations. Recently, Reisberg and Olson (1980b) studied the reactions of several isocyanides with deoxyHb and interpreted the data on the basis of the two-state model with remarkable consistency. We have used a similar model for analyzing the reaction time course of methyl isocyanide with 2 ß2 and 2ß2€0 (Scheme II).…”

Section: Data Treatmentmentioning

confidence: 99%

“…Since k7 » k5, the species a2(CO)02Me1 is never populated sufficiently to allow accurate estimation of k6. Therefore, this constant was kept fixed at the values reported by Reisberg and Olson (1980b) : ke6 = 83 s'1; ka6 =140 s'1. Constants 1 and 3 and constants 4 and 2 and, therefore, were assumed to be statistically related: k{ = 2k2, &4 = lk2.…”

Section: Data Treatmentmentioning

confidence: 99%

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Double-mixing kinetic studies of the reactions of methyl isocyanide and carbon monoxide with diliganded intermediates of hemoglobin: .alpha.2CO.beta.2 and .alpha.2.beta.2CO

Berjis¹,

Bandyopadhyay²,

Sharma³

1990

Biochemistry

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Kinetics of the reactions of CO and methyl isocyanide with two diliganded intermediates of hemoglobin, alpha 2CO beta 2 and alpha 2 beta 2CO, have been studied by double-mixing and microperoxidase methods. The valency hybrids were prepared by high-pressure liquid chromatography. The reaction time courses of ligand combination and dissociation with both of the ligands were biphasic, and in CO combination reaction the zero-time amplitudes of the two phases were independent of the protein concentration. In the presence of 2 M urea the reaction time course was clearly dependent on protein concentration, as the zero-time amplitude of the fast phase increased at lower protein concentrations. These two observations indicate that little dissociation of tetramers into dimers occurs in the absence of urea. Consistent with this, the kinetic data for the reactions of CO best fit a reaction model consisting of two tetrameric species not in rapid equilibrium with each other. Various considerations, however, suggest that the reaction model is more appropriately described as 2D in equilibrium R in equilibrium T. The reaction of triliganded species (Hb4(CO)2Me1) with methyl isocyanide was monophasic, and the reaction model suggested a fast T in equilibrium R structural change after the binding of the third ligand. Although the precise structural nature of the two species remains undefined, it is concluded that the biphasicity in the reactions of the two hybrids is characteristic of the diliganded species only and is independent of the nature of the ligand.

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Section: Data Treatmentmentioning

confidence: 99%

Section: Data Treatmentmentioning

confidence: 99%

Section: Data Treatmentmentioning

confidence: 99%

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Double-mixing kinetic studies of the reactions of methyl isocyanide and carbon monoxide with diliganded intermediates of hemoglobin: .alpha.2CO.beta.2 and .alpha.2.beta.2CO

Berjis¹,

Bandyopadhyay²,

Sharma³

1990

Biochemistry

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“…[75][76][77] Thus, other than functioning as oxygen carrier and oxidant scavenger, hemoglobin itself can sense intracellular pH changes and serve as a good buffering system. 76,78,79 These data raise intriguing perspectives on what additional roles neuronal hemoglobin may play following tMCAO, which increases both ROS and proton concentration. To better interpret how GPR68 achieves its neuroprotective function, it will be important to establish a causal relationship between GPR68 signaling and neuronal Neuroprotective in preventing phagocytosis and the associated oxidative burst 69,70 Tagln Transgelin Protective during myocardial ischemia 71 Notes: The table summarizes the downregulated genes in GPR68−/− at baseline and after ischemia, as compared to WT brain at baseline or WT ipsilateral brain after tMCAO, respectively.…”

Section: Discussionmentioning

confidence: 96%

“…One important property of hemoglobin is that the oxygenated and deoxygenated forms of hemoglobin have pKa of ~6.8 and ~7.8, respectively 75‐77 . Thus, other than functioning as oxygen carrier and oxidant scavenger, hemoglobin itself can sense intracellular pH changes and serve as a good buffering system 76,78,79 . These data raise intriguing perspectives on what additional roles neuronal hemoglobin may play following tMCAO, which increases both ROS and proton concentration.…”

Section: Discussionmentioning

confidence: 99%

RNA‐Seq analysis of knocking out the neuroprotective proton‐sensitive GPR68 on basal and acute ischemia‐induced transcriptome changes and signaling in mouse brain

2021

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Brain acid signaling plays important roles in both physiological and disease conditions. One key neuronal metabotropic proton receptor in the brain is GPR68, which contributes to hippocampal long-term potentiation (LTP) and mediates neuroprotection in acidotic and ischemic conditions. Here, to gain greater understanding of GPR68 function in the brain, we performed mRNA-Seq analysis in mice. First, we studied sham-operated animals to determine baseline expression. Compared to wild type (WT), GPR68−/− (KO) brain downregulated genes that are enriched in Gene Ontology (GO) terms of misfolding protein binding, response to organic cyclic compounds, and endoplasmic reticulum chaperone complex. Next, we examined the expression profile following transient middle cerebral artery occlusion (tMCAO). tMCAO-upregulated genes cluster to cytokine/chemokine-related functions and immune responses, while tMCAO-downregulated genes cluster to channel activities and synaptic signaling. For proton-sensitive receptors, tMCAO downregulated ASIC1a and upregulated GPR4 and GPR65, but had no effect on ASIC2, PAC, or GPR68. GPR68 deletion did not alter the expression of these proton receptors, either at baseline or after ischemia. Lastly, we performed GeneVenn analysis of differential genes at baseline and post-tMCAO. Ischemia upregulated the expression of three hemoglobin genes, along with H2-Aa, Ppbp, Siglece, and Tagln, in WT but not in KO. Immunostaining showed that tMCAO-induced hemoglobin localized to neurons. Western blot analysis further showed that hemoglobin induction is GPR68dependent. Together, these data suggest that GPR68 deletion at baseline disrupts chaperone functions and cellular signaling responses and imply a contribution of hemoglobin-mediated antioxidant mechanism to GPR68-dependent neuroprotection in ischemia.

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