Metabolism of Oxalate in Humans: A Potential Role Kynurenine Aminotransferase/Glutamine Transaminase/Cysteine Conjugate Betalyase Plays in Hyperoxaluria

Abstract

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.

Cysteine conjugate beta-lyase 2 (CCBL2) expression as a prognostic marker of survival in breast cancer patients

“…According to previous studies, CCBL2 facilitated the clearance of nephrotoxic substances [ 26 ]. The expression of CCBL2 was also decreased in patients with hyperoxaluria [ 27 ]. Moreover, CCBL2 expression was positively correlated with the occurrence of hospital-acquired VTE [ 19 ].…”

Metabolic Heterogeneity, Plasticity, and Adaptation to “Glutamine Addiction” in Cancer Cells: The Role of Glutaminase and the GTωA [Glutamine Transaminase—ω-Amidase (Glutaminase II)] Pathway

“…Mammalian tissues exhibit at least four enzymes capable of catalyzing transamination of l -kynurenine (KAT1 through KAT4). KAT4 is identical to mitochondrial aspartate aminotransferase (AspAT), whereas KAT1 and KAT3 are identical to GTK and GTL, respectively [ 2 , 3 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 ]. The l -glutamine transaminase activities of KAT1 and KAT3 are discussed in more detail below ( Section 5 ).…”

“…Failure to convert glyoxylate to glycine by an aminotransferase (peroxisomal alanine aminotransferase) mistargeted to mitochondria results in hyperoxaluria type 1 and potentially the formation of renal calculi (calcium oxalate stones) ([ 88 ] and references cited therein). The l -glutamine transaminases may play a role in preventing the accumulation of potentially toxic oxalate in the kidneys by removing the precursor, glyoxylate [ 40 ].…”

Oxalate (dys)Metabolism: Person-to-Person Variability, Kidney and Cardiometabolic Toxicity

“…The putative involvement of mitochondrial kynurenine aminotransferase-III in glyoxylate-to-glycine conversion was also recently postulated and merits careful further examination [ 35 ].…”