OXIDATION OF PHENYLALANINE TO OXALATE

苯丙氨酸氧化成草酸盐

• 批准号: 7951419
• 负责人: ROSS P HOLMES
• 金额: $ 0.97万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951419
• 关键词: Acids; Alanine-glyoxylate aminotransferase; Amino Acids; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Funding; Glycine; Glycolates; Glyoxylates; Grant; Hepatocyte; Human; Hydroxyproline; Individual; Institution; Kidney; Label; Liver; Metabolism; Oxalates; Oxalic Acids; Pathology; Pathway interactions; Patients; Phenylalanine; Primary Hyperoxaluria; Production; Rattus; Reporting; Research; Research Personnel; Resources; Source; Tyrosine; United States National Institutes of Health; enol; glyoxylate; glyoxylate reductase; oxidation; phenylpyruvate; urinary

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 了解内源性草酸合成的途径并确定减少草酸生成的策略可能对患有原发性高草酸尿症的人有利。草酸是新陈代谢的最终产物，主要在肝脏中合成。草酸的主要前体是乙醛酸，通常通过丙氨酸转氨酶(AGT)或乙醛酸还原酶(GR)还原为甘氨酸。在原发性高草酸尿症患者中，AGT或GR缺乏，草酸合成量增加，这可能导致肾脏病理。到目前为止，草酸的可能来源包括：羟脯氨酸、甘氨酸、苯丙氨酸、酪氨酸和乙醇酸。我们之前的研究(IRB#00003128)使用13C标记的甘氨酸显示，尿草酸中有5%来自甘氨酸分解。苯丙氨酸是一种氨基酸，据报道在大鼠体内代谢后会产生草酸。我们最近观察到，培养的人肝细胞也可以将13C-1苯丙氨酸转化为13C-1草酸，这表明这一途径可能在人类中起作用。苯丙氨酸在人体内的代谢主要发生在其转化为酪氨酸之后，但苯丙氨酸也可以脱氨基形成苯丙酮酸。这种酸可以形成一种不稳定的烯醇，并分解成草酸。确定苯丙氨酸氧化对全身草酸合成的贡献可能有助于开发限制草酸合成的治疗策略。