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 . 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

Ethanolamine

Ethanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...

 (designated plasmenylethalomines) or choline

Choline

Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....

 (designated plasmenylcholines).

Functions

Plasmalogens are found in numerous human tissues, which particular enrichment in the nervous, immune, and cardiovascular system . 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 .

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. 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 . 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 aldehyde

Aldehyde

An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

s. In turn, the later reacted with a fuchsine

Fuchsine

Fuchsine or rosaniline hydrochloride is a magenta dye with chemical formula C20H19N3·HCl. There are other similar chemical formulations of products sold as fuchsine, and several dozen other synonyms of this molecule....

-sulfurous acid

Sulfurous acid

Sulfurous acid is the chemical compound with the formula H2SO3. There is no evidence that sulfurous acid exists in solution, but the molecule has been detected in the gas phase...

 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 .

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 . 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 Disease, X-linked adrenoleukodystrophy, and Down syndrome

Down syndrome

Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...

.

Plasmalogens and Evolution

In addition to mammals, plasmalogens are also found in invertebrates and single cell organisms protozoans. Among bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 they have been found in many anaerobic species including Clostridia

Clostridia

The Clostridia are a class of Firmicutes, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the genus Clostridium are all Gram-positive and have the ability to...

, Megasphaera, and Veillonella

Veillonella

Veillonella are gram-negative anaerobic cocci. This bacterium is well known for its lactate fermenting abilities. They are a normal bacterium in the intestines and oral mucosa of mammals...

. Plasmalogens have been shown to have a complex evolutionary history based on the fact that their biosynthetic pathways differ in aerobic and anaerobic organisms .

Recently, it has been demonstrated that the red blood cells of humans and great apes (chimpanzees, bonobos

Bonobos

Bonobos is a dub band from Osaka, Japan. They formed in August of 2001. Their current lineup includes; Chunho Sai , Yasuyuki Sasaki , Natsuko Morimoto , Bondo Tsuji and Izumi Matsui...

, gorillas, and orangutans) have differences in their plasmalogen composition . Total RBC plasmalogen levels were found to be lower in humans than bonobos

Bonobos

Bonobos is a dub band from Osaka, Japan. They formed in August of 2001. Their current lineup includes; Chunho Sai , Yasuyuki Sasaki , Natsuko Morimoto , Bondo Tsuji and Izumi Matsui...

, 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.