Protein homeostasis defects of alanine-glyoxylate aminotransferase: new therapeutic strategies in primary hyperoxaluria type I.

[primary hyperoxaluria type 1]

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 .

Diseases
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Diseases presenting "severe inborn error" symptom

primary hyperoxaluria type 1

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