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PMC:7204663 / 2770-6576 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
53 2500-2507 Chemical denotes dibasic
56 94-103 Chemical denotes nitrogens MESH:D009584
57 1455-1457 Chemical denotes H2 MESH:D003903
61 3489-3492 Gene denotes Ka1 Gene:2900
62 3497-3500 Gene denotes Ka2 Gene:2901
63 2844-2853 Chemical denotes nitrogens MESH:D009584

2_test

Id Subject Object Predicate Lexical cue
32389720-23378628-48149094 923-924 23378628 denotes 7
32389720-3067757-48149095 925-926 3067757 denotes 8
32389720-3067757-48149096 1318-1319 3067757 denotes 8
T71350 923-924 23378628 denotes 7
T29944 925-926 3067757 denotes 8
T50414 1318-1319 3067757 denotes 8

LitCovid-PD-FMA-UBERON

Id Subject Object Predicate Lexical cue fma_id
T8 3-12 Body_part denotes Lysosomal http://purl.org/sig/ont/fma/fma63836
T9 293-300 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T10 333-342 Body_part denotes lysosomal http://purl.org/sig/ont/fma/fma63836
T11 647-655 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T12 700-708 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T13 758-762 Body_part denotes back http://purl.org/sig/ont/fma/fma25056
T14 772-779 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T15 848-857 Body_part denotes lysosomes http://purl.org/sig/ont/fma/fma63836
T16 1118-1125 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T17 1139-1147 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T18 1757-1766 Body_part denotes lysosomes http://purl.org/sig/ont/fma/fma63836
T19 1830-1839 Body_part denotes lysosomal http://purl.org/sig/ont/fma/fma63836
T20 2087-2095 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T21 2140-2148 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T22 2198-2202 Body_part denotes back http://purl.org/sig/ont/fma/fma25056
T23 2212-2219 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T24 2292-2301 Body_part denotes lysosomes http://purl.org/sig/ont/fma/fma63836
T25 2323-2332 Body_part denotes lysosomal http://purl.org/sig/ont/fma/fma63836
T26 2611-2620 Body_part denotes lysosomes http://purl.org/sig/ont/fma/fma63836
T27 2631-2638 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T28 2904-2912 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T29 2913-2917 Body_part denotes back http://purl.org/sig/ont/fma/fma25056
T30 2927-2934 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T31 3041-3049 Body_part denotes lysosome http://purl.org/sig/ont/fma/fma63836
T32 3179-3183 Body_part denotes back http://purl.org/sig/ont/fma/fma25056
T33 3191-3198 Body_part denotes cytosol http://purl.org/sig/ont/fma/fma66836
T34 3752-3761 Body_part denotes lysosomes http://purl.org/sig/ont/fma/fma63836

LitCovid-PD-MONDO

Id Subject Object Predicate Lexical cue mondo_id
T3 547-549 Disease denotes BH http://purl.obolibrary.org/obo/MONDO_0010873
T4 732-734 Disease denotes BH http://purl.obolibrary.org/obo/MONDO_0010873
T5 1989-1991 Disease denotes BH http://purl.obolibrary.org/obo/MONDO_0010873
T6 2172-2174 Disease denotes BH http://purl.obolibrary.org/obo/MONDO_0010873

LitCovid-PD-CLO

Id Subject Object Predicate Lexical cue
T19 3-12 http://purl.obolibrary.org/obo/GO_0005764 denotes Lysosomal
T20 181-190 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membranes
T21 333-342 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomal
T22 453-454 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T23 482-483 http://purl.obolibrary.org/obo/CLO_0001021 denotes B
T24 507-516 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membranes
T25 522-523 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T26 577-586 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membranes
T27 647-655 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T28 700-708 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T29 784-785 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T30 848-857 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomes
T31 890-893 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T32 1139-1147 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T33 1350-1353 http://purl.obolibrary.org/obo/CLO_0051582 denotes has
T34 1601-1602 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T35 1656-1657 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T36 1757-1766 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomes
T37 1830-1839 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomal
T38 1895-1896 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T39 1924-1925 http://purl.obolibrary.org/obo/CLO_0001021 denotes B
T40 1949-1958 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membranes
T41 1964-1965 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T42 2019-2028 http://purl.obolibrary.org/obo/UBERON_0000158 denotes membranes
T43 2085-2086 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T44 2087-2095 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T45 2140-2148 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T46 2224-2225 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T47 2292-2301 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomes
T48 2323-2332 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomal
T49 2400-2401 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T50 2422-2423 http://purl.obolibrary.org/obo/CLO_0001020 denotes A
T51 2498-2499 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T52 2518-2519 http://purl.obolibrary.org/obo/CLO_0001021 denotes B
T53 2589-2590 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T54 2611-2620 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomes
T55 2904-2912 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T56 3041-3049 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosome
T57 3603-3604 http://purl.obolibrary.org/obo/CLO_0001020 denotes a
T58 3752-3761 http://purl.obolibrary.org/obo/GO_0005764 denotes lysosomes

LitCovid-PD-CHEBI

Id Subject Object Predicate Lexical cue chebi_id
T30 13-16 Chemical denotes ion http://purl.obolibrary.org/obo/CHEBI_24870
T31 266-271 Chemical denotes drugs http://purl.obolibrary.org/obo/CHEBI_23888
T32 605-609 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T33 876-879 Chemical denotes ion http://purl.obolibrary.org/obo/CHEBI_24870
T34 1369-1374 Chemical denotes group http://purl.obolibrary.org/obo/CHEBI_24433
T35 1455-1457 Chemical denotes H2 http://purl.obolibrary.org/obo/CHEBI_18276
T36 1477-1483 Chemical denotes proton http://purl.obolibrary.org/obo/CHEBI_24636
T37 1840-1843 Chemical denotes ion http://purl.obolibrary.org/obo/CHEBI_24870
T38 2047-2051 Chemical denotes drug http://purl.obolibrary.org/obo/CHEBI_23888
T39 2333-2336 Chemical denotes ion http://purl.obolibrary.org/obo/CHEBI_24870
T40 2700-2708 Chemical denotes molecule http://purl.obolibrary.org/obo/CHEBI_25367
T41 3101-3109 Chemical denotes molecule http://purl.obolibrary.org/obo/CHEBI_25367
T42 3232-3235 Chemical denotes ion http://purl.obolibrary.org/obo/CHEBI_24870
T43 3370-3372 Chemical denotes H2 http://purl.obolibrary.org/obo/CHEBI_18276
T44 3393-3395 Chemical denotes H2 http://purl.obolibrary.org/obo/CHEBI_18276
T45 3415-3421 Chemical denotes proton http://purl.obolibrary.org/obo/CHEBI_24636

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T23 0-25 Sentence denotes 2 Lysosomal ion-trapping
T24 26-191 Sentence denotes If the pH of the molecular environment is lower (more acidic), more nitrogens are protonated, which in turn hinders the now-charged moieties from crossing membranes.
T25 192-312 Sentence denotes This is particularly relevant for the intracellular distribution of basic drugs crossing between the cytosol (pH approx.
T26 313-360 Sentence denotes 7.4) and the acidic lysosomal space (pH approx.
T27 361-366 Sentence denotes 5.0).
T28 367-411 Sentence denotes Fig. 2 shows this distribution conceptually.
T29 412-587 Sentence denotes Basic compounds are in an equilibrium of a less polar unionized form (B) that can easily cross membranes, and a polar protonated form (BH+) that cannot easily cross membranes.
T30 588-780 Sentence denotes As the unionized drug enters the acidic environment of the lysosome, it will be protonated and ‘trapped’ in the lysosome as the protonated form BH+ cannot easily diffuse back into the cytosol.
T31 781-858 Sentence denotes As a result, high concentrations of the compound can accumulate in lysosomes.
T32 859-928 Sentence denotes This concept of “ion-trapping” has been described and reviewed [7,8].
T33 929-1158 Sentence denotes The magnitude of this accumulation depends on the mathematical relationship of the pKa of the compound of interest, its permeability, and the pH gradient between the two environments (e.g. cytosol [pH 7.4] and lysosome [pH 5.0]).
T34 1159-1321 Sentence denotes If there is no permeability limitation, the expected ratio or concentration gradient can be calculated based on the well-known Henderson-Hasselbalch equation [8].
T35 1322-1593 Sentence denotes If the compound of interest has only one basic group, the ratio between the concentrations will be:(1) R=C1C2=H1+KaH2+Kawhere H1 and H2 are the respective proton concentrations (=10−pH) of the two environments (pH 5 and 7.4) and Ka is the dissociation constant (=10−pKa).
T36 1594-1700 Sentence denotes Fig. 3 A shows the magnitude of the resulting accumulation as a function of the pKa value of the compound.
T37 1701-1811 Sentence denotes Accumulation of up to 250-fold higher concentrations in lysosomes can be explained by the described mechanism.
T38 1812-1853 Sentence denotes Fig. 2 Concept of lysosomal ion-trapping.
T39 1854-2029 Sentence denotes Basic compounds are in an equilibrium of a less polar unionized form (B) that can easily cross membranes, and a polar protonated form (BH+) that cannot easily cross membranes.
T40 2030-2220 Sentence denotes As the unionized drug enters the acidic environment of a lysosome, it will be protonated and ‘trapped’ in the lysosome as the protonated form BH+ cannot easily diffuse back into the cytosol.
T41 2221-2302 Sentence denotes As a result, high concentrations of the compound can accumulate in the lysosomes.
T42 2303-2395 Sentence denotes Fig. 3 Magnitude of lysosomal ion-trapping depending on the pKa of the compound of interest.
T43 2396-2493 Sentence denotes For a monobasic compound (A), up to 250-fold higher concentrations are possible depending on pKa.
T44 2494-2563 Sentence denotes For a dibasic compound (B), the accumulation can be over 60 000-fold.
T45 2564-2640 Sentence denotes These simulations assume a pH gradient of 5.0 (lysosomes) and 7.4 (cytosol).
T46 2641-2750 Sentence denotes However, in cases where there are two basic centers in the molecule, this effect is considerably potentiated.
T47 2751-2935 Sentence denotes 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.
T48 2936-3050 Sentence denotes Furthermore, both species are in equilibrium with the biprotonated species, which is also trapped in the lysosome.
T49 3051-3199 Sentence denotes Therefore, there are three different forms of the molecule (two monoprotonated and one biprotonated) that cannot easily diffuse back to the cytosol.
T50 3200-3252 Sentence denotes This tremendously magnifies the ion-trapping effect.
T51 3253-3541 Sentence denotes 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).
T52 3542-3688 Sentence denotes 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.
T53 3689-3806 Sentence denotes Accumulation of up to 60 000-fold higher concentrations in the lysosomes can be explained by the described mechanism.