Serine C-palmitoyltransferase

In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction: palmitoyl-CoA + L-serine CoA + 3-dehydro-D-sphinganine + CO2 Thus, the two substrates of this enzyme are palmitoyl-CoA and L-serine, whereas its 3 products are CoA, 3-dehydro-D-sphinganine, and CO2. This reaction is a key step in the biosynthesis of sphingosine which is a precursor of many other sphingolipids. This enzyme participates in sphingolipid metabolism. It employs one cofactor, pyridoxal phosphate. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating). Other names in common use include: serine palmitoyltransferase, SPT, 3-oxosphinganine synthetase, and acyl-CoA:serine C-2 acyltransferase decarboxylating. Serine C-palmitoyltransferase is a member of the AOS (a-oxoamine synthase) family of PLP-dependent enzymes, which catalyse the condensation of amino acids and acyl-CoA thioester substrates. The human enzyme is a heterodimer consisting of two monomeric subunits known as long chain base 1 and 2 (LCB1/2) encoded by separate genes. The active site of LCB2 contains lysine and other key catalytic residues that are not present in LCB1, which does not participate in catalysis but is nevertheless required for the synthesis and stability of the enzyme. As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes and . The PLP (pyridoxal 5′-phosphate)-dependent serine C-palmitoyltransferase carries out the first enzymatic step of de novo sphingolipid biosynthesis. The enzyme catalyses a Claisen-like condensation between L-serine and an acyl-CoA thioester (CoASH) substrate (typically C16-palmitoyl) or an acyl-ACP (acyl-carrier protein) thioester substrate, to form 3-ketodihydrosphingosine. Initially PLP cofactor is bound to the active-site lysine via a Schiff base to form the holo-form or internal aldimine of the enzyme.