Revisiting the Glucose Kinase Superfamily: From Origins to the Evolution of Metabolism

The glucose kinase superfamily, which includes enzymes such as hexokinases and glucokinases, plays a central role in energy metabolism across all domains of life. This study explores their evolutionary origins, functional diversity, and adaptation to ecological niches, tracing their journey from early life forms to modern organisms. Recent advances reveal how these enzymes have diversified, with some retaining broad specificity, while others evolved high substrate specificity, reflecting the metabolic demands of their environments. By integrating phylogenetic, structural, and functional analyses, this work sheds light on the evolutionary pressures that shaped these enzymes and their role in metabolic innovation, not only deepening our understanding of life's biochemical evolution but also connecting ancient metabolic pathways to contemporary cellular processes.