Phosphorolysis

Phosphorolysis is a chemical reaction in which a bond is cleaved by inorganic phosphate (Pi), resulting in the incorporation of a phosphate group into one of the products. It is distinct from hydrolysis, in which water is the attacking nucleophile and typically yields a free sugar or alcohol and a phosphate or phosphate ester.

In carbohydrate metabolism, phosphorolysis is exemplified by glycogen phosphorylase, which cleaves α-1,4-glycosidic bonds in glycogen to produce glucose-1-phosphate and a shortened glycogen chain. Similar reactions occur with starch, where starch phosphorylase generates glucose-1-phosphate from starch polymers. The glucose-1-phosphate can be converted to glucose-6-phosphate and enter glycolysis or other pathways, providing an energy-yielding route that avoids free glucose formation.

In nucleotide and nucleoside metabolism, nucleoside phosphorylases catalyze phosphorolysis of nucleosides to a free base and ribose-1-phosphate or deoxyribose-1-phosphate. This salvage pathway enables reutilization of nucleosides for nucleotide synthesis and energy metabolism, particularly in tissues that rely on recycling rather than de novo synthesis.

Mechanistically, Pi acts as a nucleophile that attacks a targeted bond, leading to cleavage and transfer of the phosphate to one fragment. The resulting products are typically a sugar phosphate or a phosphorylated sugar and a released leaving group, rather than a free molecule produced by hydrolysis.

Phosphorolysis plays a key role in energy metabolism, carbohydrate breakdown, and nucleotide salvage, offering an alternative route to bond cleavage that preserves phosphate groups for subsequent metabolic use.