OXIDATION OF PHENYLALANINE TO OXALATE

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding the pathways of endogenous oxalate synthesis and identifying strategies that decrease oxalate production could be beneficial for individuals with primary hyperoxaluria. Oxalic acid is an end product of metabolism and is synthesized mainly in the liver. The main precursor of oxalate is glyoxylate and it is normally transaminated to glycine by alanine; glyoxylate aminotransferase (AGT) or reduced to glycolate by glyoxylate reductase (GR). In patients with primary hyperoxaluria either AGT or GR is deficient and the amount of oxalate synthesized increases which can cause renal pathology. The possible sources of oxalate identified to date include the amino acids: hydroxyproline, glycine, phenylalanine, tyrosine, and glycolate. Our previous study (IRB#00003128) using 13C-labeled glycine revealed that <5% of urinary oxalate is derived from glycine breakdown. Phenylalanine is an amino acid that has been reported to yield oxalate following its metabolism in rats. We have recently observed that human liver cells in culture can also convert 13 C-1 phenylalanine to 13 C-1 oxalate indicating that this pathway may function in humans. The metabolism of phenyalanine in humans occurs primarily following its conversion to tyrosine but phenylalanine can also be deaminated to form phenylpyruvate. This acid can form an unstable enol and break down to oxalate. Identifying the contribution of phenylalanine oxidation to total body oxalate synthesis could be helpful in developing therapuetic strategies that limit oxalate synthesis.