The Three Main Functions of Plasmalogens (C102)

Plasmalogens neutralize peroxides, they modulate membrane structure and the function of membrane proteins, and they modulate the efficiency and ease of vesicular release of neurotransmitters. They are obligate to life.   

To access the FREE seminars with full presentations and videos please visit Dr. Goodenowe’s resource site here. This is the article for seminar C102, Supplements (Series C).

Plasmalogens are a type of glycerophospholipid. Glycerophospholipids are the building material your body uses to make biological walls, or membranes. Your body contains trillions of cells, and each cell is like a suite in a high-rise apartment building. Each unit is separated from the others by a strong outer wall. Also, each cell contains internal compartments called organelles, such as mitochondria or peroxisomes, and these organelles are also separated from each other by membranes. The body compartmentalizes its activities much like we separate our kitchen from our bathroom from our bedroom. Just like in our house, these internal walls are less rigid. All the cells are connected to our circulatory system and all the intracellular organelles are connected to the internal cytoplasm of the cell.  

Many types of glycerophospholipids exist. But they all share common characteristics. They are all built on a glycerol backbone molecule. Think of glycerol as a 3-outlet power strip to which you can connect various attachments. The olive oil in your pantry is a glycerolipid that has the essential omega-9 fatty acid, oleic acid, plugged into each of the three outlets. Olive oil is a triacylglycerol. Glycerophospholipids have a polar phosphate group plugged into the end outlet, called the sn-3 position. This is called the head group. Several types of phosphate head groups exist, but the two main ones are phosphocholine and phosphoethanolamine. The polar head groups like the water part of a cell and are called hydrophilic (the vinegar part of an oil and vinegar dressing). The other two positions contain fatty acids (like olive oil) and they like to associate with the lipid or oily part of the cell and are called lipophilic. The first position, the sn-1 position, contains one of three anchor fatty acids (palmitic, stearic, or oleic). The middle position contains the bioactive fatty acid and is where the body stores most of its omega-3 fatty acids, like DHA. Together the sn-1 and sn-2 positions are called the tails. A glycerophospholipid that does not contain an sn-2 fatty acid is called a lysophospholipid.  

Glycerophospholipids self-organize into membranes by forming a phospholipid bilayer where the lipophilic tails mingle together to form an impermeable oily center, and the polar head groups face out from each other into the aqueous environment. Proteins are embedded in the membrane and they act like doors and vents that allow materials to pass through the membrane and move in and out of the cells and the compartments within the cells. These doors and vents are key coded so that only glucose can go through a glucose door, for example. Each of these proteins is anchored in the membrane; the membrane holds them in place. The fluidity of these membranes is tightly regulated. The yin and yang are cholesterol/phosphatidylcholine (PC) and polyunsaturated fatty acid (PUFA) containing ethanolamine plasmalogens (PLE) and phosphatidylethanolamines (PE). Higher levels of cholesterol and PC result in stiffer, more rigid membranes. Higher levels of PUFA-PLE and PUFA-PE result in more fluid membranes. 

Plasmalogens are a unique type of glycerophospholipid. Plasmalogens have a fatty alcohol at the sn-1 position instead of a fatty acid like other glycerophospholipids. All the building blocks for regular glycerophospholipids can be easily obtained from our diet. However, only minimal amounts of plasmalogens can be obtained from the diet. Plasmalogens are synthesized in a unique organelle called the peroxisome. Virtually all the cells of the body contain peroxisomes. This same organelle also performs the final step in synthetizing the essential long-chain omega-3 fatty acid, docosahexaenoic acid, otherwise known as DHA. The unique physiochemical properties that give plasmalogens their special powers also make them unstable outside the body. When you eat food containing plasmalogens, most of them get degraded by the strongly acidic environment in your stomach before they can be absorbed.  

The unique sn-1 vinyl ether bond in plasmalogens gives them three special powers. The first special power makes them the body’s dominant free radical scavenger. The unique vinyl ether bond is exquisitely sensitive to free radicals and reactive oxygen species, especially peroxides. Your body does not depend on getting plasmalogens from your diet because you can typically make as many of them as you need. Plasmalogens are designed to be sacrificed to protect nutrients that must be obtained from your diet, such as essential omega-3 and omega-6 fatty acids that your body cannot make. Other antioxidants, like vitamin E, are only lipid soluble. So, they only prevent oxidation on the inside of the membrane, but the plasmalogen vinyl ether bond is positioned close to the polar head group so that it is located near the border between the membrane and the aqueous environment. Therefore, plasmalogens are the first line of defense, and internal membrane antioxidants like vitamin E are the last line of defense. 

The second special power of plasmalogens is their membrane modulation effect. Depending on the sn-2 fatty acid, plasmalogens can create either a very tightly packed membrane or a very fluid membrane and everything in-between. For example, all your neurons are encased by a myelin sheath that performs a similar function to the insulating coating that encases an electrical cord in your house. This myelin sheath performs two functions. First, it protects your neurons from being damaged by external oxidative degradation and secondly, it prevents the internal transmission of the nerve impulse from leaking out. A neuron impulse can travel long distances in the body without losing its intensity due to its myelin sheath. Myelin contains the highest concentration of plasmalogens in the body. Approximately 80% of the ethanolamine content of the myelin sheath is plasmalogen, and the vast majority of these plasmalogens contain the monounsaturated omega-9 fatty acid oleic acid at the sn-2 position. In this situation, the plasmalogens create a very solid impervious coating, just like the insulation you have on a regular copper wire. On the opposite side of the spectrum and described in greater detail in Chapter 12, the level of DHA-plasmalogens in cellular membranes modulate the fluidity of the membrane and regulate the functions of proteins embedded in the membrane. Two important examples are the ability of a cell to efflux cholesterol and the ability of a neuron to properly metabolize the amyloid precursor protein (APP).  

The third and final special power of plasmalogens is their ability to form an inverse hexagonal phase. As I introduced in Chapter 3, the formation of this phase is a biophysical process, and it is necessary for neuronal transmission and for the brain to create its quantum computing powers. Your brain can only maintain that activity level if it has sufficient levels of plasmalogens in the synapse to enable the fusion and release of neurotransmitters and sufficient levels of plasmalogens in the myelin sheath to enable signal transmission from one neuron to another. This basic physiological process, common to all neurons in the human brain, is independent of the type of neuron, neurotransmitter, or postsynaptic receptor. Over 100 different presynaptic neurotransmitters have been identified. Most neurons are identified by the type of neurotransmitter used by that neuron. Each type of neuron can communicate with a multiplicity of different types of neurons. Accordingly, each neuron type contains receptors from multiple different types of neurotransmitters. Most neurotransmitters react with many different types of postsynaptic receptors. You can think of neurotransmitters as master keys that can open many different doors and the neurotransmitter receptors as these different doors. These neurotransmitters and their receptors have been the targets of decades of pharmaceutical research which has resulted in a cornucopia of psychoactive agents. All these drugs modify brain neuron action. Depending on the target, they either enhance or inhibit specific neuron activities. None of these drugs affect the basic physiology of the brain. Their activities are dependent upon the basic physiology of the brain being intact. 

At its most fundamental level, the brain is controlled by negative feedback or inhibitory mechanisms. I often tell people to think of the brain as a team of racing horses pulling a wagon and to imagine themselves restraining the horses with a tight hold on the reigns. If you want to turn the horses to the right, all you have to do is slightly release your hold on the left-hand side reins and vice versa. We have such fine motor skills and quick wit because the brain is like a pre-compressed spring, always ready and waiting to be released. Neurological decline affects both the loading or pre-compressing of the spring and the ability to control the spring. Impairments in cognition and mobility happen when the excitatory neuron system (the team of horses or pre-compressed spring) is weakened. This is manifested when normal functioning becomes stilted or lacks its normal smoothness or readiness of function. Mood impairments or uncontrolled motor activity occur when the inhibitory neuron system (the reigns) is weakened. These excitatory and inhibitory systems become increasingly in tune with each other as we develop from infants to children to adults. The human brain does not fully mature until our 50s. By then, the balance in these systems has become the most efficient it will ever be. However, this efficiency comes at the cost of plasticity. It is harder to teach old dogs new tricks, but they are really good at the old ones. 

Reduced cognition is one of the first, most prevalent, and most noticeable functional declines of the human brain. Around age 60, we start to see neuropathological changes in the brain. Accordingly, the neuropathological changes that correlate with and are associated with reduced mental function have been the most studied. 

Dr. Goodenowe explains the relevant research and literature regarding three main biological functions of plasmalogens in seminar C102 – The Three Main Function of Plasmalogens.