It’s not often that substitutes can do a satisfactory job at, well, substituting.  In the culinary world, swapping baking powder for baking soda doesn’t work.  Even babysitters who are called upon to substitute in child supervision might be duds.  Substituting one molecule for another in the human body is a certain catastrophe.  Such is the case for the amino acid, serine, and the molecules that try to stand in for it.

Amino acids are the building blocks of proteins, the substances of muscle, tendons, organs, glands, nails and hair.  Growth, repair and maintenance of all cells depend on them.  After water, protein accounts for the body’s largest fraction of mass, about 16%.  Those amino acids that must come from diet are known as essential.  Those that the body can make from other amino acids or from different sources are non-essential.  Serine is one of these.  But being non-essential does not mean unneeded.

Upon completion of the human genome project, science is now attending to the human “proteome,” the catalog of all human proteins.  So intricate and precise is this cavalcade that these molecules seem almost mystical.  The function of a protein depends on its shape.  If the shaping process goes awry, the ensuant malformed proteins cause problems that run from bad to worse.  Bad ones forget to do what they were expected to do; worse proteins form amorphous, sticky clumps inside cells and actually “gum the works.”

There may be as many as a hundred thousand unique proteins within a human cell.  Wow! Proteins are the tireless laborers of a cell, each with a specific task, some structural, some acting as ushers that move substances to specific locations, and some that catalyze the reactions that allow cells to divide and grow.  Talk about diversity.  But they all share a common characteristic…they fold to portray their destiny.

The destiny of serine is to help metabolize fats and fatty acids, to monitor muscle growth, to maintain the immune system, to orchestrate the manufacture of the myelin sheath that covers nerve fibers, and to help DNA and RNA do their jobs.  Of course, serine is a component of phosphatidylserine (PS), the active signaling entity that faces the cytoplasm of a cell and directs the function of myriad other intercellular materials.  Upon extracellular exposure, PS triggers blood clotting and serves as the “eat me” signal for clearance of apoptotic cells.  Inside the cell, PS directs a number of physiological pathways, including the kinases that escort phosphate groups and the G proteins that act as molecular switches.

L-serine may be derived from glycine and, under some circumstances, become essential, thus making it important in maintaining health.  It’s highly concentrated in cellular membranes, where its essential nature is demonstrated in cell proliferation, aberrations of which may be seen in psychiatric and neurological diseases, thereby underscoring the value of L-serine in brain development and function. There exists also a dextro- isomer of serine, D-serine, an anti-psychotic molecule found in the brain, where it modulates synaptic plasticity and memory.  Very low levels of this isomer are implicated in schizoid conditions.

Where substitutions of body parts—amino acids in this case—cause problems, an egregious one involves an analog of arginine called canavanine. This component of alfalfa has the capacity to induce lupus symptoms by the diminution of the mitogenic response to phytohemagglutinin and concanavalin A (that stimulate T cells), and the abrogation of concanavalin A-induced suppressor cell function, which evokes IgG response.  Purveyors of alfalfa supplements who are unaware of a client’s autoimmune status may inadvertently induce an adverse reaction to the product when trying to address conditions for which it is purported to be effective.  Serine has its copycat in an amino acid, β-N-methylamino-L-alanine (BMAA), a toxin postulated to be involved in neuromuscular and neurological disorders such as ALS and Alzheimer’s.  BMAA is known to deplete glutathione and to induce oxidative stress while killing neurons.  A provocateur in the BMAA drama is cyanobacteria, the blue-green algae that have populated the planet for eons.  BMAA has also been found in the diets of several communities indigenous to Pacific islands, where ALS is a common disorder, alleged to follow ingestion of bats whose diets include BMAA-tainted cycads.

By replacing serine, BMAA causes proteins to misfold, unfold and clump, thereby explaining the aggregation that defines neurodegenerative diseases.  What happens here is the reversal of the placement of the hydrophobic and hydrophilic components of the proteins.  They become sticky, adhere to each other, and cluster. Not too surprising, high levels of BMAA have been isolated from post-mortem ALS brain tissue.

In active dementia disease, serine replenishment may not be the panacea science had hoped to realize, but for prophylaxis it appears to be able to prevent faux-amino acids from displacing it.   Prolonged stress to the endoplasmic reticulum upregulates the Caspase-3 enzyme, that which irreversibly initiates apoptosis.  If serine is added to cells already insulted by both BMAA and the Caspase enzyme, the levels of Caspase fall (Main, 2015).  In any pathology, questions abound.  Serine used as a targeted treatment, where the amino is intended to integrate into cellular and neurological membranes, may be speculative.  On the other hand, a phosphorylated compound, such as phosphatidylserine, likely will have a more welcome outcome (Zhang, 2015).

Endogenous PS is formed when phosphatidylethanolamine (PE) swaps its ethanolamine head for a serine head to form PS when glitches in signaling are noted and / or when myelin needs protection from insult.  There is considerable presumption in thinking that serine will eliminate ALS or other neuro-entanglement that incriminates BMAA or lesser-realized causes (The ALS Untangled Group, 2017).  If serine is BMAA-specific, where does it leave neuro- patients whose etiology is otherwise?

BodyBio PC complex embraces a PE fraction that readily prepares itself for exchange of amino acids to create PS, the glycerophospholipid that has an affinity for cerebral tissue to reduce risk of dementia and cognitive function, to improve memory, and to reduce stress*.

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Brownson DM, Mabry TJ, Leslie SW.  The cycad neurotoxic amino acid, beta-N-methylamino-L-alanine (BMAA), elevates intracellular calcium levels in dissociated rat brain cells.  J Ethnopharmacol. 2002 Oct;82(2-3):159-67.

 

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Rachael Anne Dunlop, Paul Alan Cox,  Sandra Anne Banack,  and Kenneth John Rodgers.  The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation.  PLoS One. 2013; 8(9): e75376.

 

Main BJ, Dunlop RA, Rodgers KJ. The use of L-serine to prevent β-methylamino-L-alanine (BMAA)-induced proteotoxic stress in vitro. Toxicon.2016;109:7-12.

 

Moré MI, Freitas U, Rutenberg D.  Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer’s disease and dementia.  Adv Ther. 2014 Dec;31(12):1247-62.

 

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