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In vivo detection of d ‐amino acid oxidase with hyperpolarized d ‐[1‐ 13 C]alanine
Author(s) -
Radaelli Alice,
Gruetter Rolf,
Yoshihara Hikari A. I.
Publication year - 2020
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4303
Subject(s) - d amino acid oxidase , alanine , chemistry , oxidative deamination , in vivo , amino acid , oxidase test , bicarbonate , biochemistry , enzyme , biology , microbiology and biotechnology , organic chemistry
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‐ 13 C]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‐ 13 C]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‐ 13 C]alanine in the kidney and in the blood can be distinguished, underscoring the potential of d ‐[1‐ 13 C]alanine as a probe of d ‐amino acid metabolism.