STUDI KOMPUTASI MEKANISME KROMIUM(III) SEBAGAI OBAT ANTIDIABETES: INTERAKSI SENYAWA KROMIUM(III) PIKOLINAT DENGAN PUSAT AKTIF PTPCOMPUTATIONAL STUDY OF CHROMIUM(III) MECHANISM AS AN ANTIDIABETIC AGENT: INTERACTION OF CHROMIUM(III) PICOLINATE WITH ACTIVE SITE OF PTP

• Main Author: Aditama, Redi
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/34605
• Institution: Institut Teknologi Bandung

For more than two decades a chromium(III) picolinate compound, [Cr(pic)3], has been produced and consumed as type 2 antidiabetic agent. Several studies have successfully demonstrated an increase in insulin absorption and a decrease in blood glucose levels with the addition of [Cr(pic)3] in food intake. Nevertheless, the mechanism of by wich [Cr(pic)3] improves insulin absorption are still in doubt. Some researchers suspect that there is a biologically active compound that binds chromium(III) ion called chromodulin that interact directly with the insulin receptors on the cell. This interaction can enhance the absorption of insulin and reduce blood sugar levels. Another hypothesis is that chromium(III) is oxidized by biological oxidizing agents to produce chromate ion, which is a structural analog of phosphate ions. Chromate ions produced are proposed to inhibit a group of proteins that control dephosphorylation events, PTP (protein tyrosine phosphatases), after insulin binds to the insulin receptor.Inhibition of these phosphatases enhances insulin activity, which leads to decreases in blood sugar levels and increase in sugar metabolism.This research aims to study the bonding interactions of ligand-exchange products of [Cr(pic)2(OH)H2O], with the PTP active sites computationally using quantum mechanical theory. PTP proteins have a pattern of Cys(X)5Arg (where X is another amino acid residues) in the active site. The computational method used was Hartree-Fock with basis sets 6-31 G(d) for the optimization of the structure followed by energy calculations using density functional theory with the B3LYP level of correlations. The influence of solvent water is modeled by using PCM (the polarizable continuum model). The structure of [Cr(pic)2(OH)H2O] with the active centers of PTP and the value of their interaction energy was calculated. Interaction energy values were then compared with those of the H2CrO4, H3VO4, and H3PO4. Modeling results indicate that [Cr(pic)2(OH)H2O] form a bond with Cys(12) residues with an energy value of 81.92 kJ/mol, whereas the H2CrO4, H3VO4 and H3PO4 forming bonds with the same residue with energy values326.61, 338.43 and 225.79 kJ /molrespectively. These results show that H2CrO4 form bonds similar to H3VO4 that known to be effective inhibitor of PTP. In addition, H2CrO4 form a bonds that are more thermodynamically stable than those of the [Cr(pic)2(OH)H2O]. Hydrogen bonds resulting from the interaction with Arg(18) and Asp(129) residues strengthen the interaction energy to 238.13, 380.70, 450.54 and 290.38 kJ/mol for [Cr(pic)2(OH)H2O], H2CrO4, H3VO4 and H3PO4 interactios respectively.With the influence of hydrogen bonds, the value of the interaction energy of H2CrO4 with active center PTP is still higher than the interaction of [Cr(pic)2(OH)H2O] with the same active center. These calculations strengthen the hypothesis that chromium(III) that has been oxidized in biological systems enhance inhibitory interactions with PTP.