Primary hyperoxaluria type 1: AGT mistargeting highlights the fundamental differences between the peroxisomal and mitochondrial protein import pathways.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type 1 (PH 1 ) is an atypical peroxisomal disorder , as befits a deficiency of alanine :glyoxylate aminotransferase (AGT ), which is itself an atypical peroxisomal enzyme . PH 1 is characterized by excessive synthesis and excretion of the metabolic end-product oxalate and the progressive accumulation of insoluble calcium oxalate in the kidney and urinary tract . Disease in many patients is caused by a unique protein trafficking defect in which AGT is mistargeted from peroxisomes to mitochondria , where it is metabolically ineffectual , despite remaining catalytically active . Although the peroxisomal import of human AGT is dependent upon the PTS 1 import receptor PEX 5 p , its PTS 1 is exquisitely specific for mammalian AGT , suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule . This and many other functional peculiarities of AGT are probably a consequence of its rather chequered evolutionary history , during which much of its time has been spent being a mitochondrial , rather than a peroxisomal , enzyme . Analysis of the molecular basis of AGT mistargeting in PH 1 has thrown into sharp relief some of the fundamental differences between the requirements of the peroxisomal and mitochondrial protein import pathways , particularly the properties of peroxisomal and mitochondrial matrix targeting sequences and the different conformational limitations placed upon importable cargos .

Diseases
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Diseases presenting "as befits a deficiency of alanine" symptom

primary hyperoxaluria type 1

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