Affinity of zinc and copper ions for insulin monomers

• Published in: Metallomics Vol. 6; no. 7; p. 1296
• Main Authors: Gavrilova, Julia, Tõugu, Vello, Palumaa, Peep
• Format: Journal Article
• Language: English
• Published: England 01.01.2014
• Subjects: Cations, Divalent - chemistry; Copper - chemistry; HEPES - administration & dosage; Insulin - chemistry; Insulin - metabolism; Kinetics; Protein Binding - drug effects; Protein Structure, Quaternary; Spectrometry, Fluorescence; Zinc - chemistry
• ISSN: 1756-591X
• DOI: 10.1039/c4mt00059e

Zinc is an essential trace element involved in the correct packing and storage of insulin. Total zinc content in the pancreatic β-cells is among the highest in the body and changes in the Zn(2+) levels have been found to be associated with diabetes. The most common form of the Zn-insulin complex is a hexamer containing two zinc ions. However, zinc can also form other complexes with insulin, whereas dissociation constants of these complexes are not known. We have determined that the dissociation constant value of the monomeric 1 : 1 Zn-insulin complex is equal to 0.40 μM. The apparent binding affinity decreases drastically at higher insulin concentrations where the peptide forms dimers. Cu(2+) ions also bind to monomeric insulin, whereas the apparent Cu(2+)-binding affinity depends on HEPES concentration. The conditional dissociation constant of the Cu(2+)-insulin complex is equal to 0.025 μM. The analysis demonstrates that insulin cannot form complexes with zinc ions in circulation due to the low concentration of free Zn(2+) in this environment.