Structural Biochemistry/Enzyme Catalytic Mechanism/pingpong mechanism
Ping Pong is also called the double placement reaction and it means that one or more products are released before all substrates bind the enzyme. One key character of this reaction is the existence of a substituted enzyme intermediate, in which the enzyme is temporarily modified. Classic examples of this mechanism are reactions that shuttle amino groups between amino acids and a-ketoacids.
The enzyme aspartate aminotransferase catalyzes the transfer of an amino group from aspartate to a-ketoglutarate. After aspartate binds to the enzyme, the enzyme accepts aspartate’s amino group to form the substituted intermediate. The first product, oxaloacetate, departs after that. Glutamate is released as the final product after the second substrate, a-ketoglutarate binds to the enzyme and accepts the amino group from this modified enzyme.
Enzymes with a ping-pong mechanism can exist in two states, E and a chemically modified form of the enzyme E*; this modified enzyme is known as an intermediate. In such mechanisms, substrate A binds, changes the enzyme to E* by, for example, transferring a chemical group to the active site, and is then released. Only after the first substrate is released can substrate B bind and react with the modified enzyme, regenerating the unmodified E form.
Enzymes with ping–pong mechanisms include some oxidoreductases such as thioredoxin peroxidase, transferases such as acylneuraminate cytidylyltransferase, and serine proteases such as trypsin and chymotrypsin. Serine proteases are a very common and diverse family of enzymes, including digestive enzymes (trypsin, chymotrypsin, and elastase), several enzymes of the blood clotting cascade and many others. In these serine proteases, the E* intermediate is an acyl-enzyme species formed by the attack of an active site serine residue on a peptide bond in a protein substrate. A short animation showing the mechanism of chymotrypsin is linked here.
The name pingpong reaction came for the substrates appearing to bounce on and off the enzyme to a pingpong ball in the Cleland notation.