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Purine Biosynthesis Enzymes in Hippocampal Neurons

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Abstract

Despite reports implicating disrupted purine metabolism in causing a wide spectrum of neurological defects, the mechanistic details of purine biosynthesis in neurons are largely unknown. As an initial step in filling that gap, we examined the expression and subcellular distribution of three purine biosynthesis enzymes (PFAS, PAICS and ATIC) in rat hippocampal neurons. Using immunoblotting and high-resolution light and electron microscopic analysis, we find that all three enzymes are broadly distributed in hippocampal neurons with pools of these enzymes associated with mitochondria. These findings suggest a potential link between purine metabolism and mitochondrial function in neurons and provide an impetus for further studies.

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Abbreviations

PFAS:

Phosphoribosylformylglycinamidine synthase

PAICS:

Phosphoribosyl aminoimidazole succinocarboxamide synthetase

ATIC:

5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase

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Acknowledgements

We thank Drs. James P. Lata and Stephen J. Benkovic for discussions in the initial stage of this work. We also thank Dr. Fred E. Indig for assistance in confocal Airyscan imaging. This study was supported by the Intramural Research Programs of the National Institutes of Health, National Institute on Aging, and the National Institutes of Health, National Institute on Deafness and Other Communication Disorders. The Advanced Imaging Core code is ZIC DC000081.

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Authors and Affiliations

  1. Laboratory of Neurosciences, NIA/NIH, Baltimore, MD, 21224, USA

    Julie Williamson, Mark P. Mattson & Pamela J. Yao

  2. Advanced Imaging Core, NIDCD/NIH, Bethesda, MD, 20892, USA

    Ronald S. Petralia & Ya-Xian Wang

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  1. Julie Williamson
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  2. Ronald S. Petralia
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  3. Ya-Xian Wang
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  4. Mark P. Mattson
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  5. Pamela J. Yao
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Correspondence to Pamela J. Yao.

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Williamson, J., Petralia, R.S., Wang, YX. et al. Purine Biosynthesis Enzymes in Hippocampal Neurons. Neuromol Med 19, 518–524 (2017). https://doi.org/10.1007/s12017-017-8466-6

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  • DOI: https://doi.org/10.1007/s12017-017-8466-6

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