Mammalian mismatches in nucleotide metabolism: Implications for xenotransplantation

Zain I Khalpey, Ada H Y Yuen, Marialuisa Lavitrano, Christopher G A McGregor, Kameljit K. Kalsi, Magdi H. Yacoub, Ryszard T. Smolenski

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Acute humoral rejection (AHR) limits the clinical application of animal organs for xenotransplantation. Mammalian disparities in nucleotide metabolism may contribute significantly to the microvascular component in AHR; these, however remain ill-defined. We evaluated the extent of species-specific differences in nucleotide metabolism. HPLC analysis was performed on venous blood samples (nucleotide metabolites) and heart biopsies (purine enzymes) from wild type mice, rats, pigs, baboons, and human donors. Ecto-5′-nucleotidase (E5′N) activities were 4-fold lower in pigs and baboon hearts compared to human and mice hearts while rat activity was highest. Similar differences between pigs and humans were also observed with kidneys and endothelial cells. More than 10-fold differences were observed with other purine enzymes. AMP deaminase (AMPD) activity was exceptionally high in mice but very low in pig and baboon hearts. Adenosine deaminase (ADA) activity was highest in baboons. Adenosine kinase (AK) activity was more consistent across different species. Pig blood had the highest levels of hypoxanthine, inosine and adenine. Human blood uric acid concentration was almost 100 times higher than in other species studied. We conclude that species-specific differences in nucleotide metabolism may affect compatibility of pig organs within a human metabolic environment. Furthermore, nucleotide metabolic mismatches may affect clinical relevance of animal organ transplant models. Supplementation of deficient precursors or application of inhibitors of nucleotide metabolism (e.g., allopurinol) or transgenic upregulation of E5′N may overcome some of these differences.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume304
Issue number1-2
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Heterologous Transplantation
Metabolism
Swine
Nucleotides
Papio
Animal Structures
5'-Nucleotidase
Blood
Rats
Animals
AMP Deaminase
Adenosine Kinase
Inosine
Transplants
Allopurinol
Hypoxanthine
Adenosine Deaminase
Biopsy
Endothelial cells
Adenine

Keywords

  • Adenosine
  • Cytoprotection
  • Ecto-5′-nucleotidase
  • Xenotransplantation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Khalpey, Z. I., Yuen, A. H. Y., Lavitrano, M., McGregor, C. G. A., Kalsi, K. K., Yacoub, M. H., & Smolenski, R. T. (2007). Mammalian mismatches in nucleotide metabolism: Implications for xenotransplantation. Molecular and Cellular Biochemistry, 304(1-2), 109-117. https://doi.org/10.1007/s11010-007-9491-9

Mammalian mismatches in nucleotide metabolism : Implications for xenotransplantation. / Khalpey, Zain I; Yuen, Ada H Y; Lavitrano, Marialuisa; McGregor, Christopher G A; Kalsi, Kameljit K.; Yacoub, Magdi H.; Smolenski, Ryszard T.

In: Molecular and Cellular Biochemistry, Vol. 304, No. 1-2, 10.2007, p. 109-117.

Research output: Contribution to journalArticle

Khalpey, ZI, Yuen, AHY, Lavitrano, M, McGregor, CGA, Kalsi, KK, Yacoub, MH & Smolenski, RT 2007, 'Mammalian mismatches in nucleotide metabolism: Implications for xenotransplantation', Molecular and Cellular Biochemistry, vol. 304, no. 1-2, pp. 109-117. https://doi.org/10.1007/s11010-007-9491-9
Khalpey, Zain I ; Yuen, Ada H Y ; Lavitrano, Marialuisa ; McGregor, Christopher G A ; Kalsi, Kameljit K. ; Yacoub, Magdi H. ; Smolenski, Ryszard T. / Mammalian mismatches in nucleotide metabolism : Implications for xenotransplantation. In: Molecular and Cellular Biochemistry. 2007 ; Vol. 304, No. 1-2. pp. 109-117.
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