Plasmalogen

Plasmalogens are a type of ether phospholipid characterized by the presence of a vinyl ether linkage at the sn-1 position and an ester linkage at the sn-2 position.[1][2][3] In mammals, the sn-1 position is typically derived from C16:0, C18:0, or C18:1 fatty alcohols while the sn-2 position is most commonly occupied by polyunsaturated fatty acids (PUFAs). The most common head groups present in mammalian plasmalogens are ethanolamine (designated plasmenylethalomines) or choline (designated plasmenylcholines). Contents 1 Functions 2 History 3 Pathology 4 Possible Links to Common Diseases 5 Plasmalogens and Evolution 6 External links 7 References Functions Plasmalogens are found in numerous human tissues, with particular enrichment in the nervous, immune, and cardiovascular system.[1][2][3] In human heart tissue, nearly 30-40% of choline glycerophospholipids are plasmalogens. Even more striking is the fact that almost 30% of the glycerophospholipids in the adult human brain and up to 70% of myelin sheath ethanolamine glycerophospholipids are plasmalogens.[4] Although the functions of plasmalogens have not yet been fully elucidated, it has been demonstrated that they can protect mammalian cells against the damaging effects of reactive oxygen species.[1][2][3] In addition, they have been implicated as being signaling molecules and modulators of membrane dynamics. History Plasmalogens were first described by Feulgen and Voit in 1924 based on studies of tissue sections.[1] They treated these tissue sections with acid or mercuric chloride as part of a method to stain the nucleus. This resulted in the breakage of the plasmalogen vinyl-ether bond to yield aldehydes. In turn, the later reacted with a fuchsine-sulfurous acid stain used in this nuclear staining method and gave rise to colored compounds inside the cytoplasm of the cells. Plasmalogens were named based on the fact that these colored compounds were present in the "plasmal" or inside of the cell.[1] Pathology Peroxisome biogenesis disorders are autosomal recessive disorders often characterized by impaired plasmalogen biosynthesis. In these cases, the peroxisomal enzyme GNPAT, necessary for the initial steps of plasmologen biosynthesis, is mislocalized to the cytoplasm where it is inactive. In addition, genetic mutations in the GNPAT or AGPS genes can result in plasmalogen deficiencies, which lead to the development of rhizomelic chondrodysplasia punctata (RCDP) type 2 or 3, respectively.[5] In such cases, both copies of the GNPAT or AGPS gene must be mutated in order for disease to manifest. Unlike the peroxisome biogenesis disorders, other aspects of peroxisome assembly in RCDP2 and RCDP3 patients are normal as is their ability to metabolize very long chain fatty acids.Individuals with severe plasmalogen deficiencies frequently show abnormal neurological development, skeletal malformation, impaired respiration, and cataracts. Possible Links to Common Diseases Reduced levels of brain tissue plasmalogens have been associated with Alzheimer's Disease,[6][7][8][9] X-linked adrenoleukodystrophy,[10][11] and Down syndrome.[12] Plasmalogens and Evolution In addition to mammals, plasmalogens are also found in invertebrates and single cell organisms protozoans. Among bacteria they have been found in many anaerobic species including Clostridia, Megasphaera, and Veillonella. Plasmalogens have been shown to have a complex evolutionary history based on the fact that their biosynthetic pathways differ in aerobic and anaerobic organisms.[13] Recently, it has been demonstrated that the red blood cells of humans and great apes (chimpanzees, bonobos, gorillas, and orangutans) have differences in their plasmalogen composition.[3] Total RBC plasmalogen levels were found to be lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. Gene expression data from all these species caused the authors to speculate that other human and great ape cells and tissues differ in plasmalogen levels. Although the consequences of these potential differences are unknown, cross-species differences in tissue plasmalogens could influence organ functions and multiple biological processes.