PMC:7204663 / 5411-6576 JSONTXT

{"project":"LitCovid-PubTator","denotations":[{"id":"61","span":{"begin":848,"end":851},"obj":"Gene"},{"id":"62","span":{"begin":856,"end":859},"obj":"Gene"},{"id":"63","span":{"begin":203,"end":212},"obj":"Chemical"}],"attributes":[{"id":"A61","pred":"tao:has_database_id","subj":"61","obj":"Gene:2900"},{"id":"A62","pred":"tao:has_database_id","subj":"62","obj":"Gene:2901"},{"id":"A63","pred":"tao:has_database_id","subj":"63","obj":"MESH:D009584"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated. There are two different monobasic species that are produced by protonation of the respective nitrogens, and neither of these can easily diffuse from the lysosome back into the cytosol. Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome. Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol. This tremendously magnifies the ion-trapping effect. The expected accumulation ratio under these conditions is calculated as follows:(2) R=C1C2=H12+Ka1*H1+Ka1*Ka2H22+Ka1*H2+Ka1*Ka2where H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka1 and Ka2 are the dissociation constant (=10−pKa). Fig. 3B shows the magnitude of the resulting accumulation as a function of the pKa value of the compound, assuming equal values for pKa1 and pKa2. Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism."}

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T28","span":{"begin":263,"end":271},"obj":"Body_part"},{"id":"T29","span":{"begin":272,"end":276},"obj":"Body_part"},{"id":"T30","span":{"begin":286,"end":293},"obj":"Body_part"},{"id":"T31","span":{"begin":400,"end":408},"obj":"Body_part"},{"id":"T32","span":{"begin":538,"end":542},"obj":"Body_part"},{"id":"T33","span":{"begin":550,"end":557},"obj":"Body_part"},{"id":"T34","span":{"begin":1111,"end":1120},"obj":"Body_part"}],"attributes":[{"id":"A28","pred":"fma_id","subj":"T28","obj":"http://purl.org/sig/ont/fma/fma63836"},{"id":"A29","pred":"fma_id","subj":"T29","obj":"http://purl.org/sig/ont/fma/fma25056"},{"id":"A30","pred":"fma_id","subj":"T30","obj":"http://purl.org/sig/ont/fma/fma66836"},{"id":"A31","pred":"fma_id","subj":"T31","obj":"http://purl.org/sig/ont/fma/fma63836"},{"id":"A32","pred":"fma_id","subj":"T32","obj":"http://purl.org/sig/ont/fma/fma25056"},{"id":"A33","pred":"fma_id","subj":"T33","obj":"http://purl.org/sig/ont/fma/fma66836"},{"id":"A34","pred":"fma_id","subj":"T34","obj":"http://purl.org/sig/ont/fma/fma63836"}],"text":"However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated. There are two different monobasic species that are produced by protonation of the respective nitrogens, and neither of these can easily diffuse from the lysosome back into the cytosol. Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome. Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol. This tremendously magnifies the ion-trapping effect. The expected accumulation ratio under these conditions is calculated as follows:(2) R=C1C2=H12+Ka1*H1+Ka1*Ka2H22+Ka1*H2+Ka1*Ka2where H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka1 and Ka2 are the dissociation constant (=10−pKa). Fig. 3B shows the magnitude of the resulting accumulation as a function of the pKa value of the compound, assuming equal values for pKa1 and pKa2. Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T55","span":{"begin":263,"end":271},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T56","span":{"begin":400,"end":408},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T57","span":{"begin":962,"end":963},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T58","span":{"begin":1111,"end":1120},"obj":"http://purl.obolibrary.org/obo/GO_0005764"}],"text":"However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated. There are two different monobasic species that are produced by protonation of the respective nitrogens, and neither of these can easily diffuse from the lysosome back into the cytosol. Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome. Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol. This tremendously magnifies the ion-trapping effect. The expected accumulation ratio under these conditions is calculated as follows:(2) R=C1C2=H12+Ka1*H1+Ka1*Ka2H22+Ka1*H2+Ka1*Ka2where H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka1 and Ka2 are the dissociation constant (=10−pKa). Fig. 3B shows the magnitude of the resulting accumulation as a function of the pKa value of the compound, assuming equal values for pKa1 and pKa2. Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T40","span":{"begin":59,"end":67},"obj":"Chemical"},{"id":"T41","span":{"begin":460,"end":468},"obj":"Chemical"},{"id":"T42","span":{"begin":591,"end":594},"obj":"Chemical"},{"id":"T43","span":{"begin":729,"end":731},"obj":"Chemical"},{"id":"T44","span":{"begin":752,"end":754},"obj":"Chemical"},{"id":"T45","span":{"begin":774,"end":780},"obj":"Chemical"}],"attributes":[{"id":"A40","pred":"chebi_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/CHEBI_25367"},{"id":"A41","pred":"chebi_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/CHEBI_25367"},{"id":"A42","pred":"chebi_id","subj":"T42","obj":"http://purl.obolibrary.org/obo/CHEBI_24870"},{"id":"A43","pred":"chebi_id","subj":"T43","obj":"http://purl.obolibrary.org/obo/CHEBI_18276"},{"id":"A44","pred":"chebi_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/CHEBI_18276"},{"id":"A45","pred":"chebi_id","subj":"T45","obj":"http://purl.obolibrary.org/obo/CHEBI_24636"}],"text":"However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated. There are two different monobasic species that are produced by protonation of the respective nitrogens, and neither of these can easily diffuse from the lysosome back into the cytosol. Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome. Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol. This tremendously magnifies the ion-trapping effect. The expected accumulation ratio under these conditions is calculated as follows:(2) R=C1C2=H12+Ka1*H1+Ka1*Ka2H22+Ka1*H2+Ka1*Ka2where H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka1 and Ka2 are the dissociation constant (=10−pKa). Fig. 3B shows the magnitude of the resulting accumulation as a function of the pKa value of the compound, assuming equal values for pKa1 and pKa2. Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism."}

{"project":"LitCovid-sentences","denotations":[{"id":"T46","span":{"begin":0,"end":109},"obj":"Sentence"},{"id":"T47","span":{"begin":110,"end":294},"obj":"Sentence"},{"id":"T48","span":{"begin":295,"end":409},"obj":"Sentence"},{"id":"T49","span":{"begin":410,"end":558},"obj":"Sentence"},{"id":"T50","span":{"begin":559,"end":611},"obj":"Sentence"},{"id":"T51","span":{"begin":612,"end":900},"obj":"Sentence"},{"id":"T52","span":{"begin":901,"end":1047},"obj":"Sentence"},{"id":"T53","span":{"begin":1048,"end":1165},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated. There are two different monobasic species that are produced by protonation of the respective nitrogens, and neither of these can easily diffuse from the lysosome back into the cytosol. Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome. Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol. This tremendously magnifies the ion-trapping effect. The expected accumulation ratio under these conditions is calculated as follows:(2) R=C1C2=H12+Ka1*H1+Ka1*Ka2H22+Ka1*H2+Ka1*Ka2where H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka1 and Ka2 are the dissociation constant (=10−pKa). Fig. 3B shows the magnitude of the resulting accumulation as a function of the pKa value of the compound, assuming equal values for pKa1 and pKa2. Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism."}