Saturday, August 16, 2008
Alterations of fatty acid metabolism and membrane fluidity in peroxisome-defective mutant ZP102 cells
Abstract We investigated lipid composition and FA metabolism in Chinese hamster ovary (CHO-K1) cells and Pex5-mutated CHO-K1 (ZP102) cells to clarify the biochemical bases of peroxisome biogenesis disorders (PBD). ZP102 cells have defective peroxisomes and exhibit impairments of peroxisomal β-oxidation of FA and plasmalogen biosynthesis. In addition, we identified FA metabolic alterations in the synthesis of several classes of lipids in ZP102 cells. The concentration of FFA in ZP102 cells was twice that in CHO-K1 cells, but methyl esters and TAG were decreased in ZP102 cells in comparison with control cells. Also, ceramide monohexoside (CMH) concentration with ZP102 cells was significantly increased compared with the control cells. The FA molecular species, particularly the saturated to unsaturated ratios, of individual lipids also differed between the two cell types. The rate of incorporation of [14C]-labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was lugher than that in CHO-K1 cells. Lignoceric acid incorporated into cells was predominantly utilized for the synthesis of SM at 24 h after removal of [14C] lignoceric acid from the culture medium. ZP102 cells showed higher fluorescence anisotropy of 1,3,5-diphenylhexatriene, corresponding to lower membrane mobility than in CHO-K1 cells. In particular, alteration of lipid metabolism by a Pex5 mutation enhanced metabolism of saturated FA and sphingolipids. This may be related to the reduced membrane fluidity of ZP102 cells, which has been implicated in the dysfunction of membrane-linked processes in PBD.
Subscribe to:
Post Comments (Atom)
1 comment:
Symptoms & Characteristics
Peroxisome biogenesis disorders (PBDs) are comprised of genetic conditions that affect the assembly of peroxisomes. Peroxisomes are small structures within our cells that are important in fat metabolism, destroy toxic substances and recycle worn-out cell parts. Peroxisome biogenesis disorders are part of a larger group of genetic conditions called leukodystrophies. Leukodystrophies are conditions that damage the white matter of the brain and also affect how the body metabolizes particular substances in blood and organ tissues. In general, the signs and symptoms of PBDs can include:
Newborn period:
low muscle tone (hypotonia)
poor feeding
characteristic facial features (such as a flattened face; large, anterior fontanelle; widely-split cranial sutures; and a broad nasal bridge)
seizures
liver cysts and dysfunction
bone stippling (chondrodysplasia punctata) of the knee bone(s) and other long bones
Later childhood:
liver dysfunction
hearing loss/problems
vision problems
developmental delays
low muscle tone (hypotonia)
intracranial bleeding
PBDs can further be divided into separate genetic conditions based on their clinical characteristics. Some of these genetic conditions include:
Zellweger syndrome (ZS)
Symptoms appear in early infancy. Affected infants do not attain any developmental milestones and often die within the first year of life. This is the most severe of the PBDs.
Neonatal adrenoleukodystrophy (NALD)
The clinical course is variable; symptoms may appear in the newborn period or later in childhood. This condition progresses more slowly than ZS.
Infantile Refsum disease (IRD)
The clinical course is variable; symptoms may appear in the newborn period or later in childhood. This condition progresses more slowly than ZS. This is the least severe of the PBDs.
Post a Comment