Abstract

Pyridoxal 5′‐phosphate, the vitamin B6 derivative, acts as the coenzyme of many enzymes involved in amino acid metabolism. Exceptionally, this compound was found covalently bound to glycogen phosphorylase, the key enzyme in the regulation of glycogen metabolism. Although it is essential for the function of phosphorylase, its direct role has remained an enigma. We have recently found that the glucose moiety of pyridoxal (5′)diphospho (1)‐α‐D‐glucose, a conjugate of pyridoxal 5′‐phosphate and glucose 1‐phosphate through a pyrophosphate linkage, is transferred to the nonreducing end of glycogen, forming a new α‐1,4‐glucosidic linkage. This finding emphasizes the importance of the direct phosphate‐phosphate interaction between the coenzyme and the substrate in the phosphorylase catalytic reaction. We have proposed a catalytic mechanism for phosphorylase in which the phosphate group of pyridoxal 5′‐phosphate acts as an electrophile to the phosphate group of glucose 1‐phosphate. This appears to represent the first instance of the direct involvement of a phosphate group in catalysis by enzymes.