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Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding.

Varshney A, Rehan M, Subbarao N, Rabbani G, Khan RH - PLoS ONE (2011)

Bottom Line: Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination.The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding.These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

ABSTRACT
Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

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Fourier transform infrared (FTIR) measurements of HSA in absence and presence of creatinine.Infrared spectra were recorded on a FTIR spectrometer in the region 1800–1400 cm−1 at pH 7.0 (A) and pH 9.0 (B) for the free HSA, free CTN and difference spectra of HSA-CTN complexes (bottom two curves) obtained under normal serum (ACR = 5) to uremic condition (ACR = 0.25) (indicated in the figure).
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pone-0017230-g003: Fourier transform infrared (FTIR) measurements of HSA in absence and presence of creatinine.Infrared spectra were recorded on a FTIR spectrometer in the region 1800–1400 cm−1 at pH 7.0 (A) and pH 9.0 (B) for the free HSA, free CTN and difference spectra of HSA-CTN complexes (bottom two curves) obtained under normal serum (ACR = 5) to uremic condition (ACR = 0.25) (indicated in the figure).

Mentions: To investigate the effects of the uremic toxin creatinine on the secondary structure of albumin, we analyzed regions of IR spectra caused by vibrations of polypeptide backbone, viz., the amide I (1700–1600 cm−1, mainly C = O stretch) band and the amide II (1500–1600 cm−1, C-N stretching coupled with N-H bending modes) band. The amide I band of free HSA (Figure 3) had a major maximum around 1654 cm−1 for native and 1657 cm−1 for basic isomer, characteristic of the α-helical conformation [34]. Similarly, the infrared self-deconvulation and curve fitting procedures were used to determine the protein secondary structure under normal and uremic conditions both at pH 7.0 and 9.0 (Figure 4, Table 3).


Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding.

Varshney A, Rehan M, Subbarao N, Rabbani G, Khan RH - PLoS ONE (2011)

Fourier transform infrared (FTIR) measurements of HSA in absence and presence of creatinine.Infrared spectra were recorded on a FTIR spectrometer in the region 1800–1400 cm−1 at pH 7.0 (A) and pH 9.0 (B) for the free HSA, free CTN and difference spectra of HSA-CTN complexes (bottom two curves) obtained under normal serum (ACR = 5) to uremic condition (ACR = 0.25) (indicated in the figure).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046181&req=5

pone-0017230-g003: Fourier transform infrared (FTIR) measurements of HSA in absence and presence of creatinine.Infrared spectra were recorded on a FTIR spectrometer in the region 1800–1400 cm−1 at pH 7.0 (A) and pH 9.0 (B) for the free HSA, free CTN and difference spectra of HSA-CTN complexes (bottom two curves) obtained under normal serum (ACR = 5) to uremic condition (ACR = 0.25) (indicated in the figure).
Mentions: To investigate the effects of the uremic toxin creatinine on the secondary structure of albumin, we analyzed regions of IR spectra caused by vibrations of polypeptide backbone, viz., the amide I (1700–1600 cm−1, mainly C = O stretch) band and the amide II (1500–1600 cm−1, C-N stretching coupled with N-H bending modes) band. The amide I band of free HSA (Figure 3) had a major maximum around 1654 cm−1 for native and 1657 cm−1 for basic isomer, characteristic of the α-helical conformation [34]. Similarly, the infrared self-deconvulation and curve fitting procedures were used to determine the protein secondary structure under normal and uremic conditions both at pH 7.0 and 9.0 (Figure 4, Table 3).

Bottom Line: Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination.The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding.These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

ABSTRACT
Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

Show MeSH
Related in: MedlinePlus