Alkaline phosphatase superfamily members: new pieces of the choline metabolism puzzle
Abstract
Choline is an essential nutrient required for the synthesis of key molecules, such as phosphatidylcholine, sphingomyelin, acetylcholine, and S-adenosylmethionine. Choline metabolism encompasses two phases, namely the postprandial and postabsorptive states. The former enables the digestion, absorption, distribution, and storage of choline derivatives after a meal, while the latter allows the cellular utilization of choline and the mobilization of stored choline-containing molecules during fasting. Understanding choline metabolism is fundamental to the study of lipid disorders such as steatohepatitis or atherosclerosis, as well as neurodegenerative diseases, including Alzheimer's disease, and inflammatory signaling pathways. Members of the alkaline phosphatase (AP) superfamily are prominent contributors to extracellular choline metabolism. Within this family, several APs and ectonucleotide pyrophosphatases/phosphodiesterases (ENPP) members are required for physiological choline metabolism. While intestinal alkaline phosphatase (IAP) and alkaline sphingomyelinase/ ENPP7 both participate in the digestion of choline-containing derivatives in the gut during the postprandial phase, circulating ENPP2, ENPP6, and tissue-nonspecific alkaline phosphatase (TNAP) act during the postabsorptive phase to generate choline. In this review we first provide a comprehensive overview of choline metabolism and then describe how APs and ENPPs have functionally and structurally co-evolved to catalyze sequential reactions within this metabolic pathway.
Biological functions of cholineCholine is a nutrient that is required for multiple essential biological functions. It is particularly necessary for the synthesis of phosphatidylcholine, sphingomyelin, methyl donors such as S-adenosyl methionine, and acetylcholine [1]. While a fraction of choline can be endogenously
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BibTeX
@article{lecornu2026alkaline,
title = {{Alkaline phosphatase superfamily members: new pieces of the choline metabolism puzzle}},
author = {Félix Lecornu and Eva Drevet Mulard and Laurence Bessueille and Dalia Gerardin and Gilles Jean Philippe Rautureau and Lionel Ballut and David Magne},
journal = {Metabolism},
year = {2026},
month = oct,
doi = {10.1016/j.metabol.2026.156625},
url = {https://hal.science/hal-05791680v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Alkaline phosphatase superfamily members: new pieces of the choline metabolism puzzle
AU - Félix Lecornu
AU - Eva Drevet Mulard
AU - Laurence Bessueille
AU - Dalia Gerardin
AU - Gilles Jean Philippe Rautureau
AU - Lionel Ballut
AU - David Magne
PY - 2026
DA - 2026/10/11
JO - Metabolism
DO - 10.1016/j.metabol.2026.156625
UR - https://hal.science/hal-05791680v1
AB - Choline is an essential nutrient required for the synthesis of key molecules, such as phosphatidylcholine, sphingomyelin, acetylcholine, and S-adenosylmethionine. Choline metabolism encompasses two phases, namely the postprandial and postabsorptive states. The former enables the digestion, absorption, distribution, and storage of choline derivatives after a meal, while the latter allows the cellular utilization of choline and the mobilization of stored choline-containing molecules during fasting. Understanding choline metabolism is fundamental to the study of lipid disorders such as steatohepatitis or atherosclerosis, as well as neurodegenerative diseases, including Alzheimer's disease, and inflammatory signaling pathways. Members of the alkaline phosphatase (AP) superfamily are prominent contributors to extracellular choline metabolism. Within this family, several APs and ectonucleotide pyrophosphatases/phosphodiesterases (ENPP) members are required for physiological choline metabolism. While intestinal alkaline phosphatase (IAP) and alkaline sphingomyelinase/ ENPP7 both participate in the digestion of choline-containing derivatives in the gut during the postprandial phase, circulating ENPP2, ENPP6, and tissue-nonspecific alkaline phosphatase (TNAP) act during the postabsorptive phase to generate choline. In this review we first provide a comprehensive overview of choline metabolism and then describe how APs and ENPPs have functionally and structurally co-evolved to catalyze sequential reactions within this metabolic pathway. Biological functions of cholineCholine is a nutrient that is required for multiple essential biological functions. It is particularly necessary for the synthesis of phosphatidylcholine, sphingomyelin, methyl donors such as S-adenosyl methionine, and acetylcholine [1]. While a fraction of choline can be endogenously
SN - 0026-0495
SN - 1532-8600
ER -