The initial steps of
ether phospholipid biosynthesis take place in peroxisomes. Alkyl-dihydroxyacetonephosphate synthase, the peroxisomal
enzyme that actually introduces the
ether linkage, has been purified from guinea pig liver in this laboratory. With the amino acid sequences obtained from this
protein, the authors were able to clone the cDNAs encoding this
enzyme from both guinea pig and human liver. In both cases, the
enzyme appears to be synthesized as a precursor
protein with a N-terminal cleavable presequence containing a
peroxisomal targeting signal (PTS) type 2. Levels of the
enzyme protein were found to be strongly reduced in human fibroblasts derived from
Zellweger syndrome and
rhizomelic chondrodysplasia punctata patients. The molecular basis of an isolated alkyl-dihydroxyacetonephosphate synthase deficiency was resolved. A clone encoding a Caenorhabditis elegans homolog of the mammalian
enzymes was characterized. In contrast to the mammalian
enzymes, this C. elegans
enzyme lacks a N-terminal PTS type 2 motif, but carries a C-terminal PTS type 1.