d ‐amino acid oxidase (DAO) is a peroxisomal enzyme that catalyzes the oxidative deamination of several neutral and basic d ‐amino acids to their corresponding α ‐keto acids. In most mammalian species studied, high DAO activity is found in the kidney, liver, brain and polymorphonuclear leukocytes, and its main function is to maintain low circulating d ‐amino acid levels. DAO expression and activity have been associated with acute and chronic kidney diseases and with several pathologies related to N ‐methyl‐d ‐aspartate (NMDA) receptor hypo/hyper‐function; however, its precise role is not completely understood. In the present study we show that DAO activity can be detected in vivo in the rat kidney using hyperpolarized d ‐[1‐¹³C]alanine. Following a bolus of hyperpolarized d ‐alanine, accumulation of pyruvate, lactate and bicarbonate was observed only when DAO activity was not inhibited. The measured lactate‐to‐d ‐alanine ratio was comparable to the values measured when the l ‐enantiomer was injected. Metabolites downstream of DAO were not observed when scanning the liver and brain. The conversion of hyperpolarized d ‐[1‐¹³C]alanine to lactate and pyruvate was detected in blood ex vivo , and lactate and bicarbonate were detected on scanning the blood pool in the heart in vivo ; however, the bicarbonate‐to‐d ‐alanine ratio was significantly lower compared with the kidney. These results demonstrate that the specific metabolism of the two enantiomers of hyperpolarized [1‐¹³C]alanine in the kidney and in the blood can be distinguished, underscoring the potential of d ‐[1‐¹³C]alanine as a probe of d ‐amino acid metabolism.

中文翻译：

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用超极化 d-[1-13 C] 丙氨酸在体内检测 d-氨基酸氧化酶。

d-氨基酸氧化酶 (DAO) 是一种过氧化物酶体，可催化几种中性和碱性d-氨基酸氧化脱氨为相应的α-酮酸。在研究的大多数哺乳动物物种中，在肾脏、肝脏、大脑和多形核白细胞中发现高 DAO 活性，其主要功能是维持低循环d-氨基酸水平。DAO的表达和活性已经与急性和慢性肾疾病和相关的几个病状相关联Ñ甲基d天冬氨酸（NMDA）受体低/超功能; 然而，它的确切作用尚不完全清楚。在本研究中，我们表明可以在体内检测到 DAO 活性在大鼠肾脏中使用超极化d- [1- ¹³ C] 丙氨酸。在超极化的d-丙氨酸推注后，仅当 DAO 活性不受抑制时才观察到丙酮酸、乳酸和碳酸氢盐的积累。测得的乳酸与d-丙氨酸之比与注射l-对映异构体时测得的值相当。扫描肝脏和大脑时未观察到 DAO 下游的代谢物。在离体血液中检测到超极化的d- [1- ¹³ C]丙氨酸转化为乳酸和丙酮酸，在体内扫描心脏血池时检测到乳酸和碳酸氢盐。; 然而，与肾脏相比，碳酸氢盐与d-丙氨酸的比率显着降低。这些结果表明，超极化[1-的两种对映体的特定代谢¹³在肾脏和血液中的C]丙氨酸可以区分，强调的电位d - [1- ¹³ C]丙氨酸的探针d -氨基酸代谢。