PMC:7204663 / 2770-6576
Annnotations
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. |