Characterization of zinc amino acid complexes for zinc delivery in vitro using Caco-2 cells and enterocytes from hiPSC

Biometals. 2017 Oct;30(5):643-661. doi: 10.1007/s10534-017-0033-y. Epub 2017 Jul 17.


Zn is essential for growth and development. The bioavailability of Zn is affected by several factors such as other food components. It is therefore of interest, to understand uptake mechanisms of Zn delivering compounds to identify ways to bypass the inhibitory effects of these factors. Here, we studied the effect of Zn amino acid conjugates (ZnAAs) on the bioavailabilty of Zn. We used Caco-2 cells and enterocytes differentiated from human induced pluripotent stem cells from a control and Acrodermatitis enteropathica (AE) patient, and performed fluorescence based assays, protein biochemistry and atomic absorption spectrometry to characterize cellular uptake and absorption of ZnAAs. The results show that ZnAAs are taken up by AA transporters, leading to an intracellular enrichment of Zn mostly uninhibited by Zn uptake antagonists. Enterocytes from AE patients were unable to gain significant Zn through exposure to ZnCl2 but did not show differences with respect to ZnAAs. We conclude that ZnAAs may possess an advantage over classical Zn supplements such as Zn salts, as they may be able to increase bioavailability of Zn, and may be more efficient in patients with AE.

Keywords: Absorption; Acrodermatitis enteropathica; Enterocyte; Gastro-intestinal; Zip4; hIPSC.

MeSH terms

  • Acrodermatitis / drug therapy*
  • Acrodermatitis / metabolism
  • Acrodermatitis / pathology
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Amino Acids / pharmacokinetics*
  • Animals
  • Biological Availability
  • Biological Transport
  • Caco-2 Cells
  • Carrier Proteins / metabolism
  • Cell Differentiation
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacokinetics*
  • Enterocytes / cytology
  • Enterocytes / drug effects*
  • Enterocytes / metabolism
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Primary Cell Culture
  • Zinc / chemistry
  • Zinc / deficiency*
  • Zinc / metabolism
  • Zinc / pharmacokinetics*


  • Amino Acids
  • Carrier Proteins
  • Coordination Complexes
  • Zinc

Supplementary concepts

  • Acrodermatitis enteropathica