Interaction of anesthetic supplement thiopental with human serum albumin.
Thiopental (TPL) is a commonly used barbiturate anesthetic. Its binding with human serum albumin (HSA) was studied to explore the anesthetic-induced protein dysfunction. The basic binding interaction was studied by UV-absorption and fluorescence spectroscopy. An increase in the binding affinity (K) and in the number of binding sites (n) with the increasing albumin concentration was observed. The interaction was conformation-dependent and the highest for the F isomer of HSA, which implicates its slow elimination. The mode of binding was characterized using various thermodynamic parameters. Domain II of HSA was found to possess a high affinity binding site for TPL. The effect of micro-metal ions on the binding affinity was also investigated. The molecular distance, r, between donor (HSA) and acceptor (TPL) was estimated by fluorescence resonance energy transfer (FRET). Correlation between the stability of the TPL-N and TPL-F complexes and drug distribution is discussed. The structural changes in the protein investigated by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy reflect perturbation of the albumin molecule and provide an explanation for the heterogeneity of action of this anesthetic.
Khan
Shahper N
SN
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Islam
Barira
B
Rajeswari
M R
MR
Usmani
Hammad
H
Khan
Asad U
AU
D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000378:metabolism*; D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology; D002942:Circular Dichroism; D004735:Energy Transfer; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D013874:Thiopental / Q000009:adverse effects / Q000378:metabolism*
D018686:Anesthetics, Intravenous; D002413:Cations, Divalent; D012709:Serum Albumin; D013874:Thiopental