The chaperone role of the pyridoxal 5′-phosphate and its implications for rare diseases involving B6-dependent enzymes

Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview

“…In fact, while a gene therapy or an enzyme administration therapy is the only option for patients expressing catalytically inactive variants, pharmacological chaperones, small molecules able to promote the correct folding of a mutant protein [66], could rescue for conformationally-defective variants endowed with catalytic activity. In this regard, the possible application of pyridoxine treatment to mutants displaying folding defects has been claimed based on the chaperone role of the coenzyme [19]. Moreover, the identification of AGT ligands acting as pharmacological chaperones is to be hoped.…”

“…Differential scanning calorimetry studies, besides confirming the stabilizing action of PLP, have indicated that AGT denaturation follows a first-order kinetics that involves a dimeric transition state [17]. Although the absence of reversibility of the AGT unfolding does not allow drawing any thermodynamic conclusion, these results suggest that the coenzyme could have a chaperone role during the AGT folding in vivo [19].…”

Balancing of B6 Vitamers Is Essential for Plant Development and Metabolism in Arabidopsis

“…Despite the fact that PDX3 is necessary for vitamin B 6 homeostasis, we did not observe changes in the expression of the vast majority of PLP-dependent enzymes at the transcriptional level, suggesting that PDX3 effects are mediated at the posttranscriptional level. In this context, a recent study has highlighted that the stability and abundance of certain PLP-dependent enzymes may be directly affected by a low PLP content (de la Torre et al, 2006;Cellini et al, 2014).…”

“…In addition, vitamin B 6 has been shown to be an efficient reactive oxygen species quencher in vitro and is considered to act in the same capacity in vivo (Bilski et al, 2000;Havaux et al, 2009). Furthermore, it was recently suggested that PLP is important for proper folding of certain PLP-dependent enzymes, fulfilling a chaperone role (Cellini et al, 2014).…”

Effects of alanine:glyoxylate aminotransferase variants and pyridoxine sensitivity on oxalate metabolism in a cell-based cytotoxicity assay

“…Studies on normal and mutant forms of purified recombinant AGT have shown that PLP and PMP can increase AGT catalytic activity, stability and dimerization [4,21,22,25,26,51–53]. The decreased survival of cells expressing AGT-MA, AGT-mi and even AGT-170 seen at pyridoxine concentrations of 50 μM and above paralleled the paradoxical decrease in catalytic activity seen previously for AGT-MA and AGT-mi [23,48].…”