Chromium: binding studies with transferrin and peptide eeeegdd and its effect on colorectal cancer

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Date
2016
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University of Alabama Libraries
Abstract

Chromium as the trivalent ion has been proposed as an essential element for decades. Although that status has recently been discredited, doses of Cr3+ have been shown to generate improvements in insulin sensitivity and blood cholesterol levels in animals that have problems with their glucose and lipid metabolism systems, especially in type 2 diabetic rodent models. The mechanism for these effects at a molecular level is unknown. Transferrins are a class of protein that can reversibly bind 2 equivalents of metal ions. Biologically, transferrins are the main iron transport proteins in plasma. A role for transferrin in the delivery Cr3+ from plasma to tissues has been proposed. Studies have shown that Cr3+ readily binds to the two metal-binding sites in the two lobes of apotransferrin. The Cr3+ binding is accompanied by intense changes in the transferrin’s ultraviolet spectrum. This intense changes arises from chromic ion binding to two tyrosine residues in the two iron-binding sites of transferrin and allow the binding of Cr3+ to transferrin to be monitored. The rate at which Cr3+ binds to transferrin and the stability of Cr-transferrin recently has received considerable attention. In vitro spectroscopic studies previously found that the generation of Cr2-transferrin needs two weeks to guarantee a stoichiometric amount of Cr3+ binding. However, this study indicates that in the presence of 25 mM (bi)carbonate, the concentration in human blood, two Cr3+ ions bind rapidly and tightly to apotransferrin. Glycation of transferrin alters how tightly the protein binds iron and may alter the conformation of diferric transferrin, presumably changing its ability to deliver the iron to tissues. Given that Cr3+ complexes has been proposed as nutritional supplements to improve symptoms of type 2 diabetic subjects, understanding the ability of glycated transferrin to bind and transport Cr is significant, especially for determining the appropriate dose of Cr. This study examined the binding ability of Cr3+ to glycated serum transferrin and the transport of Cr in vivo by glycated transferrin. The results suggest that glycation of transferrin in subjects with elevated blood glucose levels should lower the ability of Cr from pharmacological agents to enter tissues. Additionally, these studies with glycated transferrin also indicate that heat treatment of transferrin makes dramatic change on its conformation and Cr binding ability.

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Electronic Thesis or Dissertation
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Chemistry
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