ENTPD3, also known as nucleoside triphosphate diphosphohydrolase-3 (NDPTase3) or CD39L3, is a plasma membrane-bound metabolic enzyme. It converts extracellular nucleotides into nucleosides and is involved in various pathophysiological processes such as cellular adhesion, metabolism, activation, and migration. It is part of the ectonucleotidase family and modulates purinergic signaling [1,2,3].

In gene knockout studies, Entpd3-/-mice showed no reduction in histochemical staining when ATP, ADP, AMP, or UTP were used as substrates in DRG and spinal cord tissues, indicating that deletion of Entpd3 does not impair ATP or ADP hydrolysis in primary somatosensory neurons or dorsal spinal cord [1]. Global deletion of Entpd3 (Entpd3-/-) protected against diet-induced obesity in mice. These mice consumed more calories daily, had less fecal calorie loss, and an increased basal metabolic rate on a high-fat diet, along with improved glucose tolerance [3].

In conclusion, ENTPD3 is a key enzyme in nucleotide metabolism and plays a role in processes like energy metabolism and nucleotide hydrolysis. Gene knockout mouse models have been crucial in revealing its functions in the context of obesity and neural nucleotide hydrolysis, contributing to our understanding of related physiological and disease processes.

References:

1. McCoy, Eric, Street, Sarah, Taylor-Blake, Bonnie, Wightman, Mark, Zylka, Mark. 2014. Deletion of ENTPD3 does not impair nucleotide hydrolysis in primary somatosensory neurons or spinal cord. In F1000Research, 3, 163. doi:10.12688/f1000research.4563.2. https://pubmed.ncbi.nlm.nih.gov/25717362/

2. Mo, Dan, Zeng, Zhonghong, Lin, Mingmei, Li, Rong, Yang, Yihua. 2024. Expression and Hormonal Regulation of Entpd3 at Various Estrous Cycle Stages in the Mouse Uterus. In Reproductive sciences (Thousand Oaks, Calif.), 32, 1033-1041. doi:10.1007/s43032-024-01750-1. https://pubmed.ncbi.nlm.nih.gov/39567465/

3. Sandhu, Bynvant, Perez-Matos, Maria C, Tran, Stephanie, Robson, Simon C, Jiang, Z Gordon. 2021. Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism. In Metabolism: clinical and experimental, 118, 154731. doi:10.1016/j.metabol.2021.154731. https://pubmed.ncbi.nlm.nih.gov/33631144/