12.2 Transamination

In the degradation of most standard amino acids, an early step in degradation consists in transamination, which is the transfer of the α-amino group from the amino acid to an α-keto acid. There are several different aminotransferases, each of which is specific for an individual amino acid or for a group of chemically similar ones, such as the branched amino acids leucine, isoleucine, and valine. The α-keto acid that accepts the amino group is always α-ketoglutarate (Figure 12.1-1). Transamination is freely reversible; therefore, both glutamate and α-ketoglutarate are substrates of every single transaminase. If amino groups are to be transferred between two amino acids other than glutamate, this will still occur by transient formation of glutamate (Figure 12.1-1b).

The mechanism of transamination is depicted in Figure 12.2-2 for alanine, yet is the same with all transaminases. The reaction occurs in two stages:

Transfer of the amino group from alanine to the enzyme, which releases pyruvate, and
Transfer of the amino group from the enzyme to α-ketoglutarate, which releases glutamate.

In Figure 12.2-2, only the first half-reaction is shown, since the second half-reaction is the exact reversal of the first one; this also implies that the entire reaction is reversible. Overall, the mechanism consists in the first substrate arriving and leaving before the second substrate enters and leaves; this is dubbed a Ping Pong Bi Bi reaction (Figure 12.2-1).¹ While two different substrates must be used for the the reaction to have a net effect, it is of course possible for amino acid 1 and amino acid 2 to be identical—the reaction will work just fine but achieve no net turnover.

The reaction mechanism revolves around the coenzyme pyridoxal phosphate (PLP):

At the outset of the reaction, PLP is bound as a Schiff base to the ε-amino group of a lysine residue in the active site (Figure 12.2-2a).
The bond between PLP and the enzyme is separated, and PLP forms a Schiff base with the amino acid substrate instead (Figure 12.2-2b, steps 1 and 2).
The liberated lysine residue abstracts the α hydrogen as a proton (step 3), and the electron left behind travels all the way down the PLP ring. PLP is often said to act as an 'electron sink'. This has the effect of turning the bond between the α carbon and the α nitrogen into a Schiff base.
The Schiff base is hydrolyzed to yield the α-keto acid and the amino derivative of the PLP (called pyridoxamine phosphate; steps 4 and 5).

The PLP in its various forms stays within the the active site throughout, even when not bound to the enzyme covalently. As stated above, the second half reaction is the exact reversal of the first, and you might want to draw the individual steps for yourself.

1: The mind boggles when one tries to figure out what kind of greek nomenclature Old World biochemists could have dreamed up for this.