Pyridoxal Phosphate and the Vitamin B6 Family

 
Vitamin B₆ is actually a family of related molecules consisting of a six-membered ring with a single nitrogen atom. The various members differ only in the group attached to position 4 of the ring. The ring is called a pyridine ring and the various derivatives are named after the pyridine ring (see below and Monday's Molecule #41). The most common vitamin B₆ molecules are pyridoxal or pyridoxamine. They are widely available from plant and animal sources and it's unusual for human diets to be deficient in vitamin B₆.


By definition, a vitamin is a compound that humans can no longer synthesize. Some vitamins act directly as cofactors or coenzymes but many them serve as precursors for the synthesis of the final product. This is true of the B₆ vitamins. They are rapidly converted to pyridoxal 5′-phosphate (PLP). Humans have retained the ability to catalyze this conversion.

PLP is a cofactor that's bound to many enzymes in the cell where it participates in a number of different reactions. The most important reactions are those involving transfer of amino groups from one molecule to another. There is a large class of transaminases that require PLP.

The transaminases are required for amino acid synthesis and for synthesis of many neurotransmitters such as serotonin and epinephrine. An example of a transamination reaction is shown below. Note that PLP is covalently bound to the enzyme through a lysine side chain. An amino acid donates its amino group to PLP in an exchange reaction giving rise to pyridoxamine phpsphate (PMP), which remains firmly bound to the enzyme. The entire sequence of reactions can then be reversed using any α-keto acid as a substrate to generate a new amino acid.

Many of the transaminases are evolutionarily related. Similarly, the transaminases are often related to enzymes that catalyze different PLP-reactions such as isomerizations and decarboxylations. The evidence indicates that a primitive PLP-enzyme gave rise to a number of different enzymes that make use of the basic mechanism shown below. The enzymes differ in a few amino acids that bind the substrates.