Ether lipid synthesis and its deficiency in peroxisomal disorders.
This paper deals with the discovery of plasmalogen deficiency in the cerebro-hepato-renal (Zellweger) syndrome and discusses how this has led to the development of postnatal and prenatal diagnostic procedures for this and a number of related peroxisomal disorders in man that show a general impairment in the biosynthesis of ether glycerophospholipids. The results have clearly shown an indispensable role for peroxisomes in the total process of ether lipid synthesis as evidenced by a description of the cellular topography of this process. Platelet-activating factor is a bioactive phospholipid in which the glycero-ether linkage is essential for its biological activities. The deficient formation of this lipid mediator can be correlated to the residual amounts of ether phospholipids found in patients with impaired ether lipid production. Evidence is provided to demonstrate that the extent to which cells upon stimulation produce platelet-activating factor and its 1-acyl counterpart is not caused by enzyme selectivities for ether-linked versus ester-linked phospholipid species. Rather, the relative production of these compounds appears to be mainly governed by the relative abundance of ether-linked and ester-linked precursor molecules and the activity of cellular enzymes, such as lysophospholipases, that catabolize the acyl analog of platelet-activating factor through deacylation.
van den Bosch
H
H
Centre for Biomembranes and Lipid Enzymology, Utrecht, Netherlands.
Schrakamp
G
G
Hardeman
D
D
Zomer
A W
AW
Wanders
R J
RJ
Schutgens
R B
RB
D006801:Humans; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011296:Prenatal Diagnosis / Q000379:methods; D013379:Substrate Specificity; D015211:Zellweger Syndrome / Q000175:diagnosis / Q000378:metabolism
D010742:Phospholipid Ethers; D010955:Plasmalogens; D010972:Platelet Activating Factor