the enzyme found in the Gram-negative bacterium S. paucimobilis were the first to elucidate the structure of the enzyme, revealing that PLP cofactor is held in place by several active site residues including Lys265 and His159. Specifically, the S. paucimobilis isoform features an active-site arginine residue (Arg378) that plays a key role in stabilizing the carboxy moiety of the PLP-L-serine external aldimine intermediate. Similar arginine residues in enzyme homologues (Arg370, Arg390) play analogous roles. Other homologues, such as in Sphingobacterium multivorum, feature the carboxy moiety bound to serine and methionine residues via water in place of arginine. Certain enzyme homologues, such as in S. multivorum as well as B. stolpii, are found to be associated with the inner cell membrane, thus resembling the eukaryotic enzymes. The B. stolpii homologue also features substrate inhibition by palmitoyl-CoA, a feature shared by the yeast and mammalian homologues. Clinical significance HSAN1 (hereditary sensory and autonomic neuropathy type 1) is a genetic disorder caused by mutations in either one of SPTLC1 or SPTLC2, genes encoding the two heterodimeric subunits of the eukaryotic serine C-palmitoyltransferase enzyme. These mutations have been shown to alter active site specificity, specifically by enhancing the ability of the enzyme to condense L-alanine with the palmitoyl-CoA substrate. This is consistent with elevated levels of deoxysphingoid bases formed by the condensation of alanine with palmitoyl-CoA observed in HSAN1 patients. Species distribution Serine C-palmitoyltransferase is expressed in a large number of species from bacteria to humans. The bacterial enzyme is a water-soluble homodimer whereas in eukaryotes the enzyme is a heterodimer which is anchored to the endoplasmic reticulum. Humans and other mammals express three paralogous subunits SPTLC1, SPTLC2, and SPTLC3. It was originally proposed that the functional human enzyme is a heterodimer between a SPTLC1 subunit and a second subunit which is either SPTLC2 or SPTLC3. However more recent data suggest that the enzyme may exist as a larger complex, possibly an octamer, comprising all three subunits. References EC 2.3.1 Pyridoxal phosphate enzymes Enzymes of known structure