Hyperoxaluria, excessive urinary oxalate excretion, is a significant health problem
worldwide. Disrupted oxalate metabolism has been implicated in hyperoxaluria and accordingly,
an enzymatic disturbance in oxalate biosynthesis can result in the primary hyperoxaluria.
Alanine-glyoxylate aminotransferase-1 and glyoxylate reductase, the enzymes involving
glyoxylate (precursor for oxalate) metabolism, have been related to primary hyperoxalurias.
Some studies suggest that other enzymes such as glycolate oxidase and alanine-glyoxylate
aminotransferase-2 might be associated with primary hyperoxaluria as well, but evidence of a
definitive link is not strong between the clinical cases and gene mutations. There are still
some idiopathic hyperoxalurias, which require a further study for the etiologies. Some
aminotransferases, particularly kynurenine aminotransferases, can convert glyoxylate to glycine.
Based on biochemical and structural characteristics, expression level, and subcellular
localization of some aminotransferases, a number of them appear able to catalyze the transamination
of glyoxylate to glycine more efficiently than alanine glyoxylate aminotransferase-1.
The aim of this minireview is to explore other undermining causes of primary hyperoxaluria
and stimulate research toward achieving a comprehensive understanding of underlying
mechanisms leading to the disease. Herein, we reviewed all aminotransferases in the liver for
their functions in glyoxylate metabolism. Particularly, kynurenine aminotransferase-I and III
were carefully discussed regarding their biochemical and structural characteristics, cellular
localization, and enzyme inhibition. Kynurenine aminotransferase-III is, so far, the most efficient
putative mitochondrial enzyme to transaminate glyoxylate to glycine in mammalian
livers, which might be an interesting enzyme to look for in hyperoxaluria etiology of primary
hyperoxaluria and should be carefully investigated for its involvement in oxalate metabolism.
Perspectives in primary hyperoxaluria — historical, current and future clinical interventions
