Id |
Subject |
Object |
Predicate |
Lexical cue |
T322 |
0-107 |
Sentence |
denotes |
Of interest, a small cationic inhibitor of ACE2 (but not of ACE) has been detected in plasma samples [116]. |
T323 |
108-362 |
Sentence |
denotes |
The endogenous inhibitor might play a compensatory fine-control (within a threshold limit) for normal fluctuation of ACE2 protein in plasma and it has been hypothesized to be a basic AA or a small basic peptide able to compete with ACE2 substrates [116]. |
T324 |
363-470 |
Sentence |
denotes |
I have already mentioned that AA can chelate zinc forming labile zinc complexes of amino acids (see Box 4). |
T325 |
471-656 |
Sentence |
denotes |
It is therefore possible that a basic AA or a small basic peptide capable to specifically accommodate into the catalytic site of ACE2, but into that of ACE, could inhibit ACE2 activity. |
T326 |
657-821 |
Sentence |
denotes |
Indeed, despite the similarities, ACE and ACE2 possess different substrate specificity that depends on the smaller ACE2 binding pocket compared to that of ACE [90]. |
T327 |
822-998 |
Sentence |
denotes |
This specific aspect might determine the specificity for a specific basic amino acid or molecule that is able to accommodate into the catalytic pocket of ACE2 and bind to zinc. |
T328 |
999-1159 |
Sentence |
denotes |
Among the possible endogenous ACE2 inhibitors, agmatine, decarboxylated arginine, has a chemical structure that resembles that of an ACE2 inhibitor, NAAE [127]. |
T329 |
1160-1336 |
Sentence |
denotes |
NAAE is a small molecule that had demonstrated an anti-SARS-CoV activity, by acting on both ACE2 catalytic activity and ACE2 binding domain for spike protein of SARS-CoV [127]. |
T330 |
1337-1385 |
Sentence |
denotes |
Unfortunately, NAAE has never been used in vivo. |
T331 |
1386-1676 |
Sentence |
denotes |
Indeed, NAAE is a weak ACE2 inhibitor, it is in fact more than a thousand-fold less potent than MLN-4760; however, if agmatine will be proven to have ACE2 inhibitory activity, it might be helpful to prevent the trigger of the positive feedback loops in the first mild phases of the disease. |
T332 |
1677-1799 |
Sentence |
denotes |
Indeed, it has an important role in down-regulating NO synthesis reducing NO overproduction by different mechanisms [128]. |
T333 |
1800-1961 |
Sentence |
denotes |
Of note, NOS pathway has been shown to be upregulated by both Ang (1–7)/MasR and Ang (1–9)/AT2 receptor pathways that are downstream ACE2 activity [38,39,41,43]. |
T334 |
1962-2153 |
Sentence |
denotes |
Moreover, agmatine has a regulated plasma concentration in the range of 20-80 ng/mL and the use of dietary agmatine has been shown to be safe and effective in reducing neuropathic pain [129]. |
T335 |
2154-2229 |
Sentence |
denotes |
Moreover, agmatine sulfate is regularly taken as a bodybuilding supplement. |