phosphorylation

Meaning: Phosphorylation transfers a phosphate group (PO₃²⁻), usually from ATP, onto another molecule. Kinases catalyze the addition and phosphatases remove the phosphate by hydrolysis. On proteins, the target is the hydroxyl group of serine, threonine, or tyrosine. The added negative charges change the protein's shape and interactions, so activity can go up or down. Glycogen phosphorylase is activated by phosphorylation, while glycogen synthase is inhibited. Related uses include: substrate-level phosphorylation, where a high-energy substrate such as phosphoenolpyruvate gives its phosphate to ADP; oxidative phosphorylation, where ATP synthase makes ATP using the proton gradient; phosphorylation of glucose to glucose-6-phosphate, which traps it in the cell.

On the MCAT: Passages describe signaling cascades, such as a receptor tyrosine kinase or cAMP-activated protein kinase A. You are asked to predict what happens when a kinase or phosphatase is inhibited or mutated, or to say whether an enzyme is on or off after a signal. Gel-shift or blot data may show a phosphorylated band. Reversible covalent modification is the key idea.

Common confusion: Phosphorylation does not always activate. The effect depends on the protein. Also keep kinase (adds phosphate, usually using ATP) separate from phosphatase (removes it) and from phosphorylase (cleaves a bond using inorganic phosphate).