This lesson covers the regulation of glycolysis. The principle regulation occurs at phosphofructokinase, which guards the gate to the first irreversible, committed step to burn glucose for energy. What governs it? Energy. If you need more ATP, you burn more glucose; if you don’t, you don’t. If the cell has glucose beyond its needs for energy, it uses it for the pentose phosphate pathway, which allows the production of 5-carbon sugars and antioxidant defense if needed, or stores it as glycogen if there is room. If not, glucose-6-phosphate accumulates and shuts down hexokinase. This, together with low AMPK levels, causes glucose to get left in the blood. The other key regulated step of glycolysis is pyruvate kinase, where the primary purpose of regulation is to prevent futile cycling between steps of glycolysis and gluconeogenesis. On the whole, glycolysis and glucose uptake are regulated primarily by energy status and secondarily by glucose-specific decisions about the need for glycogen or for the pentose phosphate pathway. Since we mostly use glucose for energy under most circumstances, the key regulation of the pathway is the regulation of phosphofructokinase by energy status. This means glucose uptake is largely driven by energy status, and our decisions about preventing hyperglycemia should center on total energy balance.