Phosphatidylserine decarboxylases, key enzymes of lipid metabolism.
Phosphatidylserine decarboxylases (PSDs) (E.C. 4.1.1.65) are enzymes which catalyze the formation of phosphatidylethanolamine (PtdEtn) by decarboxylation of phosphatidylserine (PtdSer). This enzymatic activity has been identified in both prokaryotic and eukaryotic organisms. PSDs occur as two types of proteins depending on their localization and the sequence of a conserved motif. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha- and beta-subunits. The S-residue set free by this cleavage serves as an attachment site of a pyruvoyl group which is required for the activity of the enzymes. Moreover, PSDs harbor characteristic binding sites for the substrate PtdSer. Substrate supply to eukaryotic PSDs requires lipid transport because PtdSer synthesis and decarboxylation are spatially separated. Targeting of PSDs to their proper locations requires additional intramolecular domains. Mitochondrially localized type I PSDs are directed to the inner mitochondrial membrane by N-terminal targeting sequences. Type II PSDs also contain sequences in their N-terminal extensions which might be required for subcellular targeting. Lack of PSDs causes various defects in different cell types. The physiological relevance of these findings and the central role of PSDs in lipid metabolism will be discussed in this review.
Schuiki
Irmgard
I
Institute of Biochemistry, Graz University of Technology, Graz, Austria.
Daum
Günther
G
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D003653:Decarboxylation; D005057:Eukaryotic Cells / Q000378:metabolism; D005544:Forecasting; D050356:Lipid Metabolism / Q000235:genetics*; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000096:biosynthesis / Q000235:genetics; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity / Q000235:genetics
D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase