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BioMed Research International
Volume 2013 (2013), Article ID 687658, 15 pages
Review Article

Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

1Departamento de Química-Física, Facultad de Ciencias, Universidad de Granada, Avenida Fuentenueva s/n, 18071 Granada, Spain
2Departamento de Cristalografía y Biología Estructural, Instituto de Química Física “Rocasolano”, Consejo Superior de Investigaciones Científicas, Serrano 119, 28006 Madrid, Spain
3Centre for Biomedical Research on Rare Diseases (CIBERER), University Hospital of the Canary Islands, and CIBICAN, University of La Laguna, 38320 Tenerife, Spain

Received 28 April 2013; Accepted 23 May 2013

Academic Editor: Barbara Cellini

Copyright © 2013 Angel L. Pey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.