TY  - JOUR
AU  - Aćimović, Jelena M.
AU  - Stanimirovic, Bojana D.
AU  - Todorović, Nina
AU  - Jovanović, Vesna B.
AU  - Mandić, Ljuba M.
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/719
AB  - Methylglyoxal (MG), a reactive alpha-oxoaldehyde that is produced in higher quantities in diabetes, uremia, oxidative stress, aging and inflammation, reacts with the thiol groups (in addition to the amino and guanidino groups) of proteins. This causes protein modification, formation of advanced glycated end products (AGEs) and cross-linking. Low molecular mass thiols can be used as competitive targets for MG, preventing the reactions mentioned above. Therefore, this paper investigated how the microenvironment of the thiol group in low molecular mass thiols (cysteine, N-acetylcysteine (NAcCys), carboxymethylcysteine (CMC) and glutathione (GSH)) and human serum albumin (HSA) affected the thiol reaction with MG. The SH group reaction course was monitored by H-1-NMR spectroscopy and spectrophotometric quantification. Changes in the HSA molecules were monitored by SDS-PAGE. The microenvironment of the SH group had a major effect on its reactivity and on the product yield. The reactivity of SH groups decreased in the order Cys > GSH > NAcCys. CMC did not react. The percentages of the reacted SH groups in the equilibrium state were almost equal, regardless of the ratio of thiol compound/MG (1:1, 1:2, 1:5): 38.1 +/- 0.9%; 38.2 +/- 0.7% and 39.0 +/- 0.8% for Cys; 26.5 +/- 0.6%; 26.6 +/- 2.6% and 27.4 +/- 2.5% for GSH; 10.8 +/- 0.9%; and 11.2 +/- 0.7% and 12.2 +/- 0.9% for NAcCys, respectively. Our results explain why substances containing alpha-amino-beta-mercapto-ethane as a pharmacophore are successful scavengers of MG. In equilibrium, HSA SH reacted in high percentages both with an insufficient amount and with an excess of MG (55% and 65%, respectively). An analysis of the hydrophobicity of the microenvironment of the SH group on the HSA surface showed that it could contribute to high levels of SH modification, leading to an increase in the scavenging activity of the albumin thiol.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Influence of the microenvironment of thiol groups in low molecular mass thiols and serum albumin on the reaction with methylglyoxal
VL  - 188
IS  - 1
SP  - 21
EP  - 30
DO  - 10.1016/j.cbi.2010.07.013
ER  - 

@article{
author = "Aćimović, Jelena M. and Stanimirovic, Bojana D. and Todorović, Nina and Jovanović, Vesna B. and Mandić, Ljuba M.",
year = "2010",
abstract = "Methylglyoxal (MG), a reactive alpha-oxoaldehyde that is produced in higher quantities in diabetes, uremia, oxidative stress, aging and inflammation, reacts with the thiol groups (in addition to the amino and guanidino groups) of proteins. This causes protein modification, formation of advanced glycated end products (AGEs) and cross-linking. Low molecular mass thiols can be used as competitive targets for MG, preventing the reactions mentioned above. Therefore, this paper investigated how the microenvironment of the thiol group in low molecular mass thiols (cysteine, N-acetylcysteine (NAcCys), carboxymethylcysteine (CMC) and glutathione (GSH)) and human serum albumin (HSA) affected the thiol reaction with MG. The SH group reaction course was monitored by H-1-NMR spectroscopy and spectrophotometric quantification. Changes in the HSA molecules were monitored by SDS-PAGE. The microenvironment of the SH group had a major effect on its reactivity and on the product yield. The reactivity of SH groups decreased in the order Cys > GSH > NAcCys. CMC did not react. The percentages of the reacted SH groups in the equilibrium state were almost equal, regardless of the ratio of thiol compound/MG (1:1, 1:2, 1:5): 38.1 +/- 0.9%; 38.2 +/- 0.7% and 39.0 +/- 0.8% for Cys; 26.5 +/- 0.6%; 26.6 +/- 2.6% and 27.4 +/- 2.5% for GSH; 10.8 +/- 0.9%; and 11.2 +/- 0.7% and 12.2 +/- 0.9% for NAcCys, respectively. Our results explain why substances containing alpha-amino-beta-mercapto-ethane as a pharmacophore are successful scavengers of MG. In equilibrium, HSA SH reacted in high percentages both with an insufficient amount and with an excess of MG (55% and 65%, respectively). An analysis of the hydrophobicity of the microenvironment of the SH group on the HSA surface showed that it could contribute to high levels of SH modification, leading to an increase in the scavenging activity of the albumin thiol.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Influence of the microenvironment of thiol groups in low molecular mass thiols and serum albumin on the reaction with methylglyoxal",
volume = "188",
number = "1",
pages = "21-30",
doi = "10.1016/j.cbi.2010.07.013"
}

Aćimović, J. M., Stanimirovic, B. D., Todorović, N., Jovanović, V. B.,& Mandić, L. M.. (2010). Influence of the microenvironment of thiol groups in low molecular mass thiols and serum albumin on the reaction with methylglyoxal. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 188(1), 21-30.
https://doi.org/10.1016/j.cbi.2010.07.013

Aćimović JM, Stanimirovic BD, Todorović N, Jovanović VB, Mandić LM. Influence of the microenvironment of thiol groups in low molecular mass thiols and serum albumin on the reaction with methylglyoxal. in Chemico-Biological Interactions. 2010;188(1):21-30.
doi:10.1016/j.cbi.2010.07.013 .

Aćimović, Jelena M., Stanimirovic, Bojana D., Todorović, Nina, Jovanović, Vesna B., Mandić, Ljuba M., "Influence of the microenvironment of thiol groups in low molecular mass thiols and serum albumin on the reaction with methylglyoxal" in Chemico-Biological Interactions, 188, no. 1 (2010):21-30,
https://doi.org/10.1016/j.cbi.2010.07.013 . .