PHOSPHATIDYLSERINE DECARBOXYLASE

Phosphatidylserine decarboxylase (PSD) is an important enzyme in the s ynthesis of phosphatidylethanolamine in both prokaryotes and eukaryote s. The cloned bacterial gene encodes an integral membrane protein that is first made as a proenzyme, and subsequently proteolyzed to an alph a subunit, containing a pyruvoyl prosthetic group, and a beta subunit. Two types of decarboxylases an found in yeast, PSD1 and PSD2, that lo calize to the inner mitochondrial membrane and the Golgi/vacuole membr ane, respectively. The mammalian enzyme is also found in the inner mit ochondrial membrane. The yeast genes and mammalian cDNA have been clon ed and sequenced. The yeast genes contain 5' sequences associated with regulation of expression by inositol and choline. The yeast PSD1 and the mammalian PSD both contain an LGST amino acid motif that identifie s the site of proteolysis and pyruvoyl prosthetic group attachment in the bacterial enzyme. The yeast PSD1 and mammalian PSD also have mitoc hondrial targeting and inner membrane sorting sequences. Processing in termediates have been defined in the mammalian enzyme that correspond to the sequential removal of the mitochondrial targeting and inner mem brane sorting sequence, followed by formation of the alpha and beta su bunits. In contrast, the PSD2 enzyme contains a putative Golgi localiz ation/retention sequence and a C2 homology domain, in addition to pred icted alpha and beta subunits. The transport requirements for substrat e access to the PSD enzymes have provided important information about lipid trafficking, and the availability of yeast mutants is likely to provide important new genetic selections in the future. (C) 1997 Elsev ier Science B.V.