[Benzylpenicillin as an allosteric effector].
Benzylpenicillin (penicillin G) is a model drug for studies of drug-protein biochemical interactions. Furthermore the literature indicates that benzylpenicillin and protein conjugation is a universal phenomenon: benzylpenicillin is known to readily conjugate to proteins-serum albumin, globulin and others peptides to modify space structure and electrophoretical properties. The aim of the study was to test if the benzylpenicillin is an allosteric effector. Serum benzylpenicillin concentration in geometric progression was used. Then acid phosphatase (AcP), alanine aminotransferase (AIAT) activity and international normalized ratio (INR) was tested. Although benzylpenicillin influences AcP and INR, only AcP activity is directly proportional to the benzylpenicillin concentration (Pc): change of AcP activity was the derivative of Pc in 76% (R2 = 0.7635). Furthermore, the benzylpenicillin appears to be uncompetitive inhibitor of acid phosphatase (inhibitory constant Ki = 95.67M; Vmax = 34.843 nKat). On the contrary no effect of AIAT activity was observed. Unexpectedly INR was modified in irregular manner: in some concentrations of benzylpenicillin INR was over 25% lower than in control probe (INR approximately 0.6 vs. 0.82). Unfortunately INR > 6.5 is accepted as an early indicator of poor prognosis in fulminant hepatic failure. This phenomenon may be useful in sepsis as a prevention of disseminated intravascular coagulation (DIC). These data indicate that high benzylpenicillin concentration may be the cause of artifacts. The facts allow of interpretation that the allosteric effect of benzylpenicillin on enzymes activity is a possible mechanism of unpredictable adverse drug reactions (i.e. intolerance).
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Zakładu Analityki Lekarskiej 4 Wojskowego Szpitala Klinicznego we Wrocławiu, Instytut Immunologii i Terapii Doświadczalnej PAN.
D000494:Allosteric Regulation / Q000187:drug effects; D000890:Anti-Infective Agents / Q000097:blood* / Q000494:pharmacology*; D006801:Humans; D010400:Penicillin G / Q000097:blood* / Q000494:pharmacology*
D000890:Anti-Infective Agents; D010400:Penicillin G