Abnormal groups phospholipids

Lysosomes are in effect a cellular waste-bin, and play an important role in the turnover and degradation of cytoplasmic organelles and phago-cytosed particles. They facilitate receptor-mediated endocytosis of many macromolecules from the cell membrane. Lysosomes carry hydrolases that degrade nucleotides, proteins, lipids and phospholipids they also remove carbohydrate, sulphate, or phosphate groups from molecules. Lysosomes store iron, either as soluble ferritin or as products of ferritin degradation, such as haemosiderin. Abnormalities associated with lysosomal function cause a variety of storage disorders such as Tay-Sachs disease [9]. 

The apoproteins are distinct physically, chemically, and immunochemically and have important roles in lipid transport and metabolism (Table 20-1). In keeping with their individual metabolic functions, they have specific structural domains. Amino acid substitutions or deletions in critical domains result in functional abnormalities. The apoproteins share a common structure in the form of an amphipathic helix, in which the amino acid residues have hydrophobic side chains on one face of the helix and hydrophilic polar residues on the other. The hydrophilic face is believed to interact with the polar head groups of the phospholipids, while the hydrophobic residues interact with their fatty acid portions. 

There is now substantial evidence from several groups that, although plasma levels of AA and other HUFAs are normal or near normal, red cell membrane phospholipid levels are reduced, particularly in patients with the negative syndrome (Peet, Laugharne, Horrobin, Reynolds, 1994 Yao, van Kammen, Welker, 1994 Glen etal., 1994). The abnormality may become more evident if red cells are not frozen immediately at very low temperatures, such as -70°C. Maintenance for a period at room temperature or for long periods at -20°C rather than -70°C is associated with loss of AA from membrane phospholipids in samples from schizophrenic patients but not from controls. This indicates increased loss of AA from membranes, a process that may continue in stored samples. 

The deleterious effect of phospholipid removal appears to be the exposure of apolar regions of the membrane protein to a polar environment. This may lead to retractions of these apolar regions with simultaneous exposure of polar groups normally buried inside. The protein molecule may thus be locked in an abnormal, inactive conformation. Reconstitution through addition of phospholipids and temporary exposure to detergent seems to allow the peptide chain to refold to its natural conformation in association with the amphi-pathic lipids, leading to normalization of the functional parameters. 

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