• Azka Lahdimawan Fakultas Kedokteran, Universitas Lambung Mangkurat, Banjarmasin, Indonesia
  • Siti Arika Bulan Fakultas Kedokteran, Universitas Lambung Mangkurat, Banjarmasin, Indonesia
  • Eko Suhartono Departemen Biokimia dan Biomolekuler, Fakultas Kedokteran, Universitas Lambung Mangkurat, Banjarbaru, Indonesia
  • Bambang Setiawan Departemen Biokimia dan Biomolekuler, Fakultas Kedokteran, Universitas Lambung Mangkurat, Banjarbaru, Indonesia
Keywords: Cadmium, Carbohydrate metabolism, Glycogen synthase, Mercury, Phosphofructokinase


Cadmium (Cd) and Mercury (Hg) is a heavy metal with high cytotoxicity, implicated as causes of chronic inflammation, oxidative stress, obesity, hyperglycemia, and even diabetes. The long-term exposure of Cd and Hg can affect enzymes involved in carbohydrate metabolism, on the process of glycolysis and glycogenesis. by changing the structure and enzymatic activity of proteins which can cause toxic effects on enzymes involved therein including glycogen synthase (GS), which can cause glycogen content depletion and has potential to limit the glycolysis process in liver and muscles by decreasing the phosphofructokinase (PFK) enzyme activity. There are not many studies that explain the interactions between Cd and Hg on GS and PFK enzymes. For this reason, this research was carried out using in silico. The structure of the enzymes was obtained from the RCSB Protein Data Bank (http://www.rcsb.org) with the following code, GS (PDB ID: 1RZV) and PFK (PDB ID: 4WLO).  The interactions between Cd and Hg with these enzymes were used by MIB: Metal Ion-Binding site prediction and docking server (http://bioinfo.cmu.edu.tw/MIB/). The interactions between Cd and amino acids of targeted protein were visualized on UCSF Chimera 1.14. The results showed that Hg interacted with amino acid residues at the active site of the glycogen synthase enzyme at the end of the C-terminal domain, namely at 3 cysteine ??residues Cys 295, cys 366, and cys 390. Meanwhile, Cd and Hg did not interact with amino acid residues. on the active site of the phosphofructokinase enzyme, but interacts with the protein structure of the enzyme.


Buschiazzo A, Ugalde JE, Guerin ME, Shepard W, Ugalde RA, Alzari PM. Crystal structure of glycogen synthase: Homologous enzymes catalyze glycogen synthesis and degradation. EMBO J. 2004;23(16):3196–205.

Chen YW, Yang CY, Huang CF, Hung DZ, Leung YM, Liu SH. Heavy metals, islet function and diabetes development. Islets. 2009; 1(3):169-76

Evans, P. R., Farrants, G. W., Hudson, P. J., Britton, H. G., Phillips, D. C., Blake, C. C. F., & Watson, H. C. (1981). Phosphofructokinase: structure and control. Philosophical Transactions of the Royal Society of London. B, Biological Sciences, 293(1063), 53-62. doi:10.1098/rstb.1981.0059

Jeon JY, Ha KH, Kim DJ. New risk factors for obesity and diabetes: Environmental chemicals. J Diabetes Investig. 2015;6(2):109–11.

Kloos M, Brüser A, Kirchberger J, et al. Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation. Biochemical Journal. 2015;469(3):421-32.

Komari N, Suhartono E. Cadmium binding to antioxidant enzymes: In silico study. IOP Conf Ser Mater Sci Eng. 2020;980(1).

Martz E. Demonstration : Noncovalen bond finder. Molviz Organization. 2021.

Mul JD, Stanford KI, Hirshman MF, Goodyear LJ. Exercise and Regulation of Carbohydrate Metabolism. Prog Mol Biol Transl Sci. 2015;135:17–37.

Palm DC, Rohwer JM, Hofmeyr JHS. Regulation of glycogen synthase from mammalian skeletal muscle - A unifying view of allosteric and covalent regulation. FEBS J. 2013;280(1):2–27.

Ramírez-Bajo MJ, de Atauri P, Ortega F, et al. Effects of cadmium and mercury on the upper part of skeletal muscle glycolysis in mice. PloS one. 2014;9(1):e80018.

Roos DH, Puntel RL, Lugokenski TH, Ineu RP, Bohrer D, Burger ME, et al. Complex methylmercury-cysteine alters mercury accumulation in different tissues of mice. Basic Clin Pharmacol Toxicol. 2010;107(4):789–92.

Sabir S, Akash MSH, Fiayyaz F, Saleem U, Mehmood MH, Rehman K. Role of cadmium and arsenic as endocrine disruptors in the metabolism of carbohydrates: Inserting the association into perspectives. Biomed Pharmacotherapy. 2019;114:108802.

Schumacher L, Abbott LC. Effects of methyl mercury exposure on pancreatic beta cell development and function. J Appl Toxicol. 2017;37(1):4–12.

Suhartono E, Komari N, Siahaan SC. Interaksi Merkuri dan Kadmium terhadap Enzim Kunci pada Glikolisis in Silico. Jurnal Ilmiah Kedokteran Wijaya Kusuma. 2021;10(2):253-60.

Tsai TL, Kuo CC, Pan WH, Wu TN, Lin P, Wang SL. Type 2 diabetes occurrence and mercury exposure – From the National Nutrition and Health Survey in Taiwan. Environ Int]. 2019;126:260–7.

Xu X, Mathieu C, Boitard SE, Dairou J, Dupret JM, Agbulut O, et al. Skeletal muscle glycogen phosphorylase is irreversibly inhibited by mercury: Molecular, cellular and kinetic aspects. FEBS Lett. 2014;588(1):138–42.

How to Cite
Lahdimawan, A., Bulan, S., Suhartono, E., & Setiawan, B. (2022). DAMPAK KADMIUM DAN MERKURI TERHADAP METABOLISME KARBOHIDRAT: KAJIAN IN SILICO PADA ENZIM GLIKOGEN SINTASE DAN FOSFOFRUKTOKINASE. Jurnal Ilmiah Ibnu Sina, 7(1), 109-115. https://doi.org/10.36387/jiis.v7i1.836