PMID- 10553003
OWN - NLM
STAT- MEDLINE
DCOM- 20000119
LR  - 20091103
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 11
DP  - 1999 Nov
TI  - Ether lipid biosynthesis: alkyl-dihydroxyacetonephosphate synthase protein
      deficiency leads to reduced dihydroxyacetonephosphate acyltransferase activities.
PG  - 1998-2003
AB  - Recent studies have indicated that two peroxisomal enzymes involved in ether
      lipid synthesis, i.e., dihydroxyacetonephosphate acyltransferase and
      alkyl-dihydroxyacetonephosphate synthase, are directed to peroxisomes by
      different targeting signals, i.e., peroxisomal targeting signal type 1 and type
      2, respectively. In this study, we describe a new human fibroblast cell line in
      which alkyl-dihydroxyacetonephosphate synthase was found to be deficient both at 
      the level of enzyme activity and enzyme protein. At the cDNA level, a 128 base
      pair deletion was found leading to a premature stop. Remarkably,
      dihydroxyacetonephosphate acyltransferase activity was strongly reduced to a
      level comparable to the activities measured in fibroblasts from patients affected
      by the classical form of rhizomelic chondrodysplasia punctata (caused by a defect
      in peroxisomal targeting signal type 2 import). Dihydroxyacetonephosphate
      acyltransferase activity was completely normal in another
      alkyl-dihydroxyacetonephosphate synthase activity-deficient patient. Fibroblasts 
      from this patient showed normal levels of the synthase protein and inactivity
      results from a point mutation leading to an amino acid substitution. These
      results strongly suggest that the activity of dihydroxyacetonephosphate
      acyltransferase is dependent on the presence of alkyl-dihydroxyacetonephosphate
      synthase protein. This interpretation implies that the deficiency of
      dihydroxyacetonephosphate acyltransferase (targeted by a peroxisomal targeting
      signal type 1) in the classic form of rhizomelic chondrodysplasia punctata is a
      consequence of the absence of the alkyl-dihydroxyacetonephosphate synthase
      protein (targeted by a peroxisomal targeting signal type 2).
FAU - de Vet, E C
AU  - de Vet EC
AD  - Centre for Biomembranes and Lipid Enzymology, Institute for Biomembranes, Utrecht
      University, Utrecht, The Netherlands.
FAU - Ijlst, L
AU  - Ijlst L
FAU - Oostheim, W
AU  - Oostheim W
FAU - Dekker, C
AU  - Dekker C
FAU - Moser, H W
AU  - Moser HW
FAU - van Den Bosch, H
AU  - van Den Bosch H
FAU - Wanders, R J
AU  - Wanders RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Phospholipid Ethers)
RN  - 0 (Plasmalogens)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.42 (glycerone-phosphate O-acyltransferase)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.26 (alkylglycerone-phosphate synthase)
SB  - IM
MH  - Acyltransferases/metabolism
MH  - Adult
MH  - Alkyl and Aryl Transferases/deficiency
MH  - Child, Preschool
MH  - Chondrodysplasia Punctata, Rhizomelic/enzymology/pathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Phospholipid Ethers/*metabolism
MH  - Plasmalogens/*biosynthesis
EDAT- 1999/12/20 00:00
MHDA- 1999/12/20 00:01
CRDT- 1999/12/20 00:00
PHST- 1999/12/20 00:00 [pubmed]
PHST- 1999/12/20 00:01 [medline]
PHST- 1999/12/20 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Nov;40(11):1998-2003.