title: PLP-dependent enzymes as entry and exit gates of sphingolipid metabolism.
abstract: Sphingolipids are membrane constituents as well as signaling molecules involved in many essential cellular processes. Serine palmitoyltransferase (SPT) and sphingosine-1-phosphate lyase (SPL), both PLP (pyridoxal 5'-phosphate)-dependent enzymes, function as entry and exit gates of the sphingolipid metabolism. SPT catalyzes the condensation of serine and a fatty acid into 3-keto-dihydrosphingosine, whereas SPL degrades sphingosine-1-phosphate (S1P) into phosphoethanolamine and a long-chain aldehyde. The recently solved X-ray structures of prokaryotic homologs of SPT and SPL combined with functional studies provide insight into the structure-function relationship of the two enzymes. Despite carrying out different reactions, the two enzymes reveal striking similarities in the overall fold, topology, and residues crucial for activity. Unlike their eukaryotic counterparts, bacterial SPT and SPL lack a transmembrane helix, making them targets of choice for biochemical characterization because the use of detergents can be avoided. Both human enzymes are linked to severe diseases or disorders and might therefore serve as targets for the development of therapeutics aiming at the modulation of their activity. This review gives an overview of the sphingolipid metabolism and of the available biochemical studies of prokaryotic SPT and SPL, and discusses the major similarities and differences to the corresponding eukaryotic enzymes.
authors.affiliation: Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Bourquin
authors.forename: Guido
authors.initials: G
authors.lastname: Capitani
authors.forename: Markus Gerhard
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051102:Serine C-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D051102:Serine C-Palmitoyltransferase; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase); D013110:Sphingosine