Selective oxidation of Zn2+ -insulin catalyzed by Cu2+.
The purpose of this study is to quantitate the sensitivity of Zn2+ -insulin to oxidation catalyzed by various redox active transition metals, Cu2+, Fe2+, Mn2+, Ni2+, Co2+, Cr3+. Human recombinant insulin (INS) was subjected to oxidation under various conditions in the presence and absence of Zn2+ and ascorbate. The extent of oxidation was monitored by RP-HPLC. Only Cu2+, but none of the other metals or combination thereof, for example, Ni2+/Co2+, Co2+/Cr3+, and Ni2+/Cr3+, catalyzed INS oxidation, for example, to an extent of 45% when 20 microM INS/8.8 microM Zn2+ were exposed to 8 microM Cu2+ and 50 microM ascorbate for 90 min. The Cu2+ -catalyzed oxidation mainly targeted the B chain of INS, where the two histidine residues are located.
Sadineni
Vikram
V
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Schöneich
Christian
C
D000975:Antioxidants / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D000975:Antioxidants; D007004:Hypoglycemic Agents; D007328:Insulin; D021122:Protein Subunits; D011994:Recombinant Proteins; D006639:Histidine; D003300:Copper; D015032:Zinc; D001205:Ascorbic Acid