Aberration in de novo ether lipid biosynthesis in peroxisomal disorders.
The Zellweger syndrome is a rare inborn error of metabolism characterized by the absence of morphologically distinguishable peroxisomes. As a consequence tissues and cells from Zellweger patients contain severely reduced levels of ether phospholipids. These are replaced by diacylphospholipids while keeping the polar headgroup composition of the cellular phospholipids constant. Both peroxisomal enzymes involved in glycero-ether lipid bond formation appear to be deficient. The experiments clearly establish that peroxisomes are indispensible for ether lipid biosynthesis. The peroxisomal deficiency in de novo ether lipid biosynthesis in fibroblasts and amniotic fluid cells can be applied in diagnostic assays. The mutation can be by-passed by feeding the cells with alkylglycerol. Similar characteristics as found for plasmalogen biosynthesis in Zellweger syndrome were assessed in other diseases with a general impairment of peroxisomal functions such as infantile Refsum disease and neonatal adrenoleukodystrophy as well as in rhizomelic chondrodysplasia punctata, a disease characterized by the absence of some, but not all, peroxisomal functions. Complementation analysis after somatic cell fusion has revealed that at least three genes must be involved in the biogenesis of fully functional peroxisomes.
van den Bosch
H
H
Biochemistry Laboratory, Utrecht, The Netherlands.
Schalkwijk
C G
CG
Schrakamp
G
G
Wanders
R J
RJ
Schutgens
R B
RB
Schram
A W
AW
Tager
J M
JM
D005995:Glyceryl Ethers / Q000378:metabolism*; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D010955:Plasmalogens / Q000096:biosynthesis; D015211:Zellweger Syndrome / Q000378:metabolism*
D005995:Glyceryl Ethers; D010955:Plasmalogens