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Abstract

We aimed to characterize the function of ADP-dependent glucokinase (adpgk), a novel glucokinase in the embryonic development of zebrafish. Our study is the first study reporting the importance of adpgk in fine-tuning glucose metabolism during the early developmental process. Knockdown of adpgk in zebrafish embryos significantly induced hexokinase1 expression and increased the glucose consumption, indicated by decreased free glucose and increased glucose-6-phosphate levels. The adpgk knockdown embryos underwent an adaptive glucose metabolism with activated pentose phosphate pathway, exhibiting a reduction in one-carbon metabolism and hexosamine biosynthesis pathway. The dysregulated N-glycans synthesis further caused malfunctioning of proteins in the developmental signaling pathways which led to deformed convergent extension during the embryonic development of zebrafish. In concert with the altered glucose homeostasis, the adpgk knockdown embryonic cells endure an acid-base imbalance and compromised anti-oxidant systems. Furthermore, the metabolic disturbance induced the activation of cell cycle checkpoints, indicated by increased cdkn1a and gadd45aa expression and apoptosis, which in turn, exacerbated the deformed embryonic body patterning. Overall, adpgk seems to act as a key regulator of glucose metabolism in the cell and thereby plays an important role in the embryonic development of zebrafish