Comparative Analysis of the Interaction of Silver Nanoparticles with Hexokinase from Trypanosoma brucei and Humans

• Published in: International journal of nanomedicine Vol. 18; pp. 1399 - 1411
• Main Authors: Mlozen, Madalitso M, Van Marwijk, Jacqueline, Wilhelmi, Brendan Shane, Whiteley, Chris
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2023; Dove; Dove Medical Press
• Subjects: Comparative analysis; Enzymes; hexokinase; Hexokinase - metabolism; Histidine; Humans; Kinetics; Metal Nanoparticles - chemistry; nanomedicine; Nanoparticles; Original Research; Silver; Silver - pharmacology; Trypanosoma brucei brucei - enzymology; trypanosomiasis; trypanosomiasis; nanomedicine; nanoparticles; hexokinase
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S401319

Regardless of the efforts to ease cases of human African trypanosomiasis (HAT), an increased number of cases get reported annually. This is because of drug resistant (Tb), the causative agent of the illness. This has renewed the need for creative methods to find new anti-trypanosomal drugs. The blood stream form (BSF) of the parasite depends exclusively on the glycolytic pathway for energy production while it is in the human host. Interruptions in this pathway efficiently kills the parasite. hexokinase ( HK) is the first enzyme in glycolysis, and any effectors or inhibitors of HK would have potential as anti-trypanosomal agents. HK and human glucokinase ( GCK) were over-expressed with a 6 histidine-tag in BL21(DE3) cells having the pRARE2 plasmid. HK had thermal and pH stability between 30°C and 55°C and 7.5 and 8.5, respectively, while GCK exhibited thermal and pH stability between 30°C and 40°C and 7.0 and 8.0, respectively. Kinetically, HK had a K of 39.3 µM, V of 0.066 µmol.min .mL , k of 2.05 min and k /K of 0.0526 min .µmol . GCK exhibited a K of 4.5 µM, V of 0.032 µnmol.min .mL , k of 11.25 min , and k /K of 2.5 min .µmol . Interaction kinetic studies of silver nanoparticles (AgNPs) (0.1 µM) of average size of 6 nm with HK and GCK were conducted. AgNPs selectively inhibited HK over GCK. HK showed a non-competitive inhibition with a 50% and 28% decrease in V , and k /k , respectively. GCK showed a 33% increase in affinity, 9% decrease in V , and a 50% increase in enzyme efficiency. The observed pattern of hGCK and AgNPs falls under the uncompetitive inhibition. The observed highly selective inhibitory effects of AgNPs between HK and GCK may be used in development of new anti-trypanosomal drugs.