Abstract：
:Supercritical carbon dioxide (CO(2)) possesses germicide (bactericide and sporicide) effect. Despite of the fact, that this effect is used in industrial sterilization processes, the sterilization mechanism at molecular level is unclear. Our hypotheses can provide a molecular-biological explanation for the phenomenon. We believe that in supercritical state CO(2) reacts competitively with Met-tRNA(fMet), the formation rate and the amount of formyl-methionyl-tRNA (fMet-tRNA(fMet)) will be diminished by irreversible substrate consumption. The fMet-tRNA(fMet) possesses a key role in prokaryotic protein synthesis, being almost exclusively the initiator aminoacyl-tRNA. The formed carbamoyl-methionyl-tRNA (cMet-tRNA(fMet)), probably stable only under pressure and high CO(2) concentration, is stabilized by forming a ternary molecular complex with the GTP-form of the translational initiation factor 2 (GTP-IF2). This complex is unable to dissociate from preinitiation 70S ribosomal complex because of strong polar binding between the protein C-2 domain and the modified initiator aminoacyl-tRNA. The IF2-fMet-tRNA(fMet)-blocked 70S ribosomal preinitiation complex does not decompose following the GTP hydrolysis, becoming unable to synthesize proteins. The death of the microbial cell is caused by inhibition of the protein synthesis and energetic depletion. Moreover, we propose a possible mechanism for the accumulation of cMet-tRNA(fMet) in the bacterial cell. Since the translational process is an important target for antibiotics, the proposed mechanism could be a work hypothesis for discovery of new antibiotics. Made by high conservative character of prokaryotic translation initiation, the proposed IF2 pathway deterioration strategy may conduct to obtaining selective (with low mammalian toxicity) antimicrobials and at the same time, with reduced possibility of the drug resistance development.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
András CD,Csajági C,Orbán CK,Albert C,Abrahám B,Miklóssy Idoi
10.1016/j.mehy.2009.08.043subject
Has Abstractpub_date
2010-02-01 00:00:00pages
325-9issue
2eissn
0306-9877issn
1532-2777pii
S0306-9877(09)00599-4journal_volume
74pub_type
杂志文章abstract：:Alzheimer's disease (AD) includes etiologically heterogeneous disorders characterized by senile or presenile dementia, extracellular amyloid protein aggregations containing an insoluble amyloid precursor protein derivative, and intracytoplasmic tau protein aggregations. Recent studies also show excess neuronal aneuplo...
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journal_title：Medical hypotheses
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pub_type： 杂志文章
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更新日期：2012-08-01 00:00:00
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pub_type： 社论
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更新日期：2008-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：1983-04-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2014-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2017-02-01 00:00:00
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更新日期：2003-11-01 00:00:00
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doi：10.1016/j.mehy.2014.07.015
更新日期：2014-10-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2002-06-01 00:00:00
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pub_type： 历史文章,杂志文章
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更新日期：2018-02-01 00:00:00
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journal_title：Medical hypotheses
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更新日期：2000-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：2012-10-01 00:00:00
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pub_type： 杂志文章
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