NMR metabolomics for understanding the role of alkaline phosphatase in neurotransmission and inflammation processes

Introduction Tissue Non-specific Alkaline Phosphatase (TNAP) is a ubiquitous ectoenzyme located in different body tissues. Mutations of the TNAP gene are responsible for hypophosphatasia, a rare disease characterized mainly by defective bone mineralization caused by pyrophosphate accumulation in bone tissue and accompanied by neurological symptoms (pain, seizure…) [1]. We aimed in identifying metabolic pathways associated with TNAP activity in brain and in exploring its role in the inflammatory process.Technological and methodological innovation Untargeted 1H NMR-based metabolomics was used on tissue extracts from two original models: (i) Akp2 mice, which is the rodent model of hypophosphatasia by invalidation of the TNAP gene and (ii) a model of postprandial inflammation based on food intake [2]. Results and impact Eight metabolites differentiated TNAP-deficient mouse brain (in 7 day-old animals), among which GABA, adenosine and cystathionine were the most discriminant [3]. Metabolic changes were also observed in both liver and brain in the postprandial inflammation model. These metabolic changes suggest that TNAP is (i) involved in the production of anti-inflammatory agents (adenosine) or their precursor (cystathionine, precursor of H2S), (ii) regulated by pro-inflammatory cytokines