Effect of glycation on human serum albumin–zinc interaction: a biophysical study
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Zinc deficiency is common in diabetes. However, the cause of this phenomenon is largely unknown. 80% of the absorbed zinc is transported through the blood in association with human serum albumin (HSA). Under persistent hyperglycemia, HSA frequently undergoes non-enzymatic glycation which can affect its structure and metal-binding function. Hence, in this study, we have examined the interaction of zinc with native and glycated HSA. The protein samples were incubated either in the presence or in the absence of physiologically elevated glucose concentration for 21 days. The samples were then analyzed for structural changes and zinc-binding ability using various spectrometric and calorimetric approaches. The study reveals changes in the three-dimensional structure of the protein upon glycation that cause local unfolding of the molecule. Most such regions are localized in subdomain IIA of HSA which plays a key role in zinc binding. This affects zinc interaction with HSA and could in part explain the perturbed zinc distribution in patients with hyperglycemia. The varying degree of HSA glycation in blood could explain the observed heterogeneity pertaining to zinc deficiency among people suffering from diabetes.
KeywordsZinc Human serum albumin (HSA) Diabetes Glycation Micronutrient
The authors are thankful to Shumaila Khan for helping with protein studies and in editing the manuscript. Sarah Iqbal is funded through UGC-SRF Scheme, Govt. of India and acknowledges the grant support.
Author contribution statement
SI and IN designed the study. SI designed the protocols. Experiments were carried out by SI, FAQ, and MA. SI and FAQ analyzed the data and wrote the manuscript with inputs from IN.
Compliance with ethical standards
Conflict of interest
Authors declare no conflict of interest.
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