Glutamate-1-semialdehyde

Glutamate-1-semialdehyde (GSA), also known as 5-aminolevulinate synthase, is a key enzyme in the biosynthesis of chlorophyll and heme. It is involved in the conversion of glutamate to delta-aminolevulinic acid (ALA), the first step in the biosynthesis of these important biological molecules.

Structure[edit | edit source]

The structure of GSA is complex, with multiple subunits and cofactors. The enzyme is a dimer, with each subunit containing a pyridoxal phosphate (PLP) cofactor. The PLP is essential for the enzyme's activity, as it forms a Schiff base with the glutamate substrate, facilitating its conversion to ALA.

File:Glutamate-1-semialdehyde structure.png

Structure of Glutamate-1-semialdehyde

Function[edit | edit source]

GSA catalyzes the conversion of glutamate to ALA in a two-step reaction. First, the enzyme binds to glutamate and the PLP cofactor, forming a Schiff base. This is then converted to an intermediate, glutamate-1-semialdehyde, through a process known as transamination. The GSA is then converted to ALA through a decarboxylation reaction.

Role in Disease[edit | edit source]

Mutations in the gene encoding GSA can lead to a variety of diseases. For example, defects in GSA are associated with porphyria, a group of rare genetic disorders that affect the nervous system and skin. In addition, GSA has been implicated in the development of certain types of cancer, as it is involved in the biosynthesis of heme, a molecule essential for the function of many proteins, including those involved in cell division and DNA repair.