PMC:7204663 / 2796-5410
Annnotations
LitCovid-PubTator
Id | Subject | Object | Predicate | Lexical cue | tao:has_database_id |
---|---|---|---|---|---|
53 | 2474-2481 | Chemical | denotes | dibasic | |
56 | 68-77 | Chemical | denotes | nitrogens | MESH:D009584 |
57 | 1429-1431 | Chemical | denotes | H2 | MESH:D003903 |
2_test
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
32389720-23378628-48149094 | 897-898 | 23378628 | denotes | 7 |
32389720-3067757-48149095 | 899-900 | 3067757 | denotes | 8 |
32389720-3067757-48149096 | 1292-1293 | 3067757 | denotes | 8 |
T71350 | 897-898 | 23378628 | denotes | 7 |
T29944 | 899-900 | 3067757 | denotes | 8 |
T50414 | 1292-1293 | 3067757 | denotes | 8 |
LitCovid-PD-FMA-UBERON
Id | Subject | Object | Predicate | Lexical cue | fma_id |
---|---|---|---|---|---|
T9 | 267-274 | Body_part | denotes | cytosol | http://purl.org/sig/ont/fma/fma66836 |
T10 | 307-316 | Body_part | denotes | lysosomal | http://purl.org/sig/ont/fma/fma63836 |
T11 | 621-629 | Body_part | denotes | lysosome | http://purl.org/sig/ont/fma/fma63836 |
T12 | 674-682 | Body_part | denotes | lysosome | http://purl.org/sig/ont/fma/fma63836 |
T13 | 732-736 | Body_part | denotes | back | http://purl.org/sig/ont/fma/fma25056 |
T14 | 746-753 | Body_part | denotes | cytosol | http://purl.org/sig/ont/fma/fma66836 |
T15 | 822-831 | Body_part | denotes | lysosomes | http://purl.org/sig/ont/fma/fma63836 |
T16 | 1092-1099 | Body_part | denotes | cytosol | http://purl.org/sig/ont/fma/fma66836 |
T17 | 1113-1121 | Body_part | denotes | lysosome | http://purl.org/sig/ont/fma/fma63836 |
T18 | 1731-1740 | Body_part | denotes | lysosomes | http://purl.org/sig/ont/fma/fma63836 |
T19 | 1804-1813 | Body_part | denotes | lysosomal | http://purl.org/sig/ont/fma/fma63836 |
T20 | 2061-2069 | Body_part | denotes | lysosome | http://purl.org/sig/ont/fma/fma63836 |
T21 | 2114-2122 | Body_part | denotes | lysosome | http://purl.org/sig/ont/fma/fma63836 |
T22 | 2172-2176 | Body_part | denotes | back | http://purl.org/sig/ont/fma/fma25056 |
T23 | 2186-2193 | Body_part | denotes | cytosol | http://purl.org/sig/ont/fma/fma66836 |
T24 | 2266-2275 | Body_part | denotes | lysosomes | http://purl.org/sig/ont/fma/fma63836 |
T25 | 2297-2306 | Body_part | denotes | lysosomal | http://purl.org/sig/ont/fma/fma63836 |
T26 | 2585-2594 | Body_part | denotes | lysosomes | http://purl.org/sig/ont/fma/fma63836 |
T27 | 2605-2612 | Body_part | denotes | cytosol | http://purl.org/sig/ont/fma/fma66836 |
LitCovid-PD-MONDO
Id | Subject | Object | Predicate | Lexical cue | mondo_id |
---|---|---|---|---|---|
T3 | 521-523 | Disease | denotes | BH | http://purl.obolibrary.org/obo/MONDO_0010873 |
T4 | 706-708 | Disease | denotes | BH | http://purl.obolibrary.org/obo/MONDO_0010873 |
T5 | 1963-1965 | Disease | denotes | BH | http://purl.obolibrary.org/obo/MONDO_0010873 |
T6 | 2146-2148 | Disease | denotes | BH | http://purl.obolibrary.org/obo/MONDO_0010873 |
LitCovid-PD-CLO
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T20 | 155-164 | http://purl.obolibrary.org/obo/UBERON_0000158 | denotes | membranes |
T21 | 307-316 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomal |
T22 | 427-428 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T23 | 456-457 | http://purl.obolibrary.org/obo/CLO_0001021 | denotes | B |
T24 | 481-490 | http://purl.obolibrary.org/obo/UBERON_0000158 | denotes | membranes |
T25 | 496-497 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T26 | 551-560 | http://purl.obolibrary.org/obo/UBERON_0000158 | denotes | membranes |
T27 | 621-629 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosome |
T28 | 674-682 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosome |
T29 | 758-759 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T30 | 822-831 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomes |
T31 | 864-867 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T32 | 1113-1121 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosome |
T33 | 1324-1327 | http://purl.obolibrary.org/obo/CLO_0051582 | denotes | has |
T34 | 1575-1576 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | A |
T35 | 1630-1631 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T36 | 1731-1740 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomes |
T37 | 1804-1813 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomal |
T38 | 1869-1870 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T39 | 1898-1899 | http://purl.obolibrary.org/obo/CLO_0001021 | denotes | B |
T40 | 1923-1932 | http://purl.obolibrary.org/obo/UBERON_0000158 | denotes | membranes |
T41 | 1938-1939 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T42 | 1993-2002 | http://purl.obolibrary.org/obo/UBERON_0000158 | denotes | membranes |
T43 | 2059-2060 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T44 | 2061-2069 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosome |
T45 | 2114-2122 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosome |
T46 | 2198-2199 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T47 | 2266-2275 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomes |
T48 | 2297-2306 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomal |
T49 | 2374-2375 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T50 | 2396-2397 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | A |
T51 | 2472-2473 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T52 | 2492-2493 | http://purl.obolibrary.org/obo/CLO_0001021 | denotes | B |
T53 | 2563-2564 | http://purl.obolibrary.org/obo/CLO_0001020 | denotes | a |
T54 | 2585-2594 | http://purl.obolibrary.org/obo/GO_0005764 | denotes | lysosomes |
LitCovid-PD-CHEBI
Id | Subject | Object | Predicate | Lexical cue | chebi_id |
---|---|---|---|---|---|
T31 | 240-245 | Chemical | denotes | drugs | http://purl.obolibrary.org/obo/CHEBI_23888 |
T32 | 579-583 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T33 | 850-853 | Chemical | denotes | ion | http://purl.obolibrary.org/obo/CHEBI_24870 |
T34 | 1343-1348 | Chemical | denotes | group | http://purl.obolibrary.org/obo/CHEBI_24433 |
T35 | 1429-1431 | Chemical | denotes | H2 | http://purl.obolibrary.org/obo/CHEBI_18276 |
T36 | 1451-1457 | Chemical | denotes | proton | http://purl.obolibrary.org/obo/CHEBI_24636 |
T37 | 1814-1817 | Chemical | denotes | ion | http://purl.obolibrary.org/obo/CHEBI_24870 |
T38 | 2021-2025 | Chemical | denotes | drug | http://purl.obolibrary.org/obo/CHEBI_23888 |
T39 | 2307-2310 | Chemical | denotes | ion | http://purl.obolibrary.org/obo/CHEBI_24870 |
LitCovid-sentences
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T24 | 0-165 | 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 | 166-286 | Sentence | denotes | This is particularly relevant for the intracellular distribution of basic drugs crossing between the cytosol (pH approx. |
T26 | 287-334 | Sentence | denotes | 7.4) and the acidic lysosomal space (pH approx. |
T27 | 335-340 | Sentence | denotes | 5.0). |
T28 | 341-385 | Sentence | denotes | Fig. 2 shows this distribution conceptually. |
T29 | 386-561 | 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 | 562-754 | 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 | 755-832 | Sentence | denotes | As a result, high concentrations of the compound can accumulate in lysosomes. |
T32 | 833-902 | Sentence | denotes | This concept of “ion-trapping” has been described and reviewed [7,8]. |
T33 | 903-1132 | 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 | 1133-1295 | 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 | 1296-1567 | 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 | 1568-1674 | Sentence | denotes | Fig. 3 A shows the magnitude of the resulting accumulation as a function of the pKa value of the compound. |
T37 | 1675-1785 | Sentence | denotes | Accumulation of up to 250-fold higher concentrations in lysosomes can be explained by the described mechanism. |
T38 | 1786-1827 | Sentence | denotes | Fig. 2 Concept of lysosomal ion-trapping. |
T39 | 1828-2003 | 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 | 2004-2194 | 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 | 2195-2276 | Sentence | denotes | As a result, high concentrations of the compound can accumulate in the lysosomes. |
T42 | 2277-2369 | Sentence | denotes | Fig. 3 Magnitude of lysosomal ion-trapping depending on the pKa of the compound of interest. |
T43 | 2370-2467 | Sentence | denotes | For a monobasic compound (A), up to 250-fold higher concentrations are possible depending on pKa. |
T44 | 2468-2537 | Sentence | denotes | For a dibasic compound (B), the accumulation can be over 60 000-fold. |
T45 | 2538-2614 | Sentence | denotes | These simulations assume a pH gradient of 5.0 (lysosomes) and 7.4 (cytosol). |