Hypopigmentation, Melanin, Immunity, Glycosylation

[fritolay66]

Some Important Facts About Glycosylation:

·Genetic disruption of various outer chain determining glycotransferases has shown in animals to give rise to viable animals that experience significant biological effects. In other words, the animal lives with disease. I think one of the significant biological effects includes the manifestation of Morgellon’s. Just MHO.

·Most pathogens and toxins can communicate with host cells (us) by mechanisms including recognition of cell surface glycans.

·Many symbiotic microbes also recognize cell surface glycans as a means to maintain symbiosis in the host (us for the context of this post).

·Molecular mimicry of higher cell surface glycans by pathogens is a highly successful strategy that is mediated primarily by microbial synthesis of cell surface glycans of the host. A great example would be Lyme Borrelia cysts?

·The protective responses of the host to invasion by pathogens is mediated by recognition of the cell surface glycans of the pathogen.

·Many important growth factors of the cell and cytokines interact specifically with their correlation glycans, in turn affecting the stability, movement, concentration, etc,. and there for control mutagenesis

[fritolay66]

Glycans

·Glycans are directly involved along with phosphorylation in directing or modulating signaling pathways.

·Glycans are the major physical components of the extracellular matrix and modulate critical interactions with other matrix components as well as cell matrix interactions.

·Several main gene families of glycan binding proteins are known as lectins. These have been shown to use sugar chains (I have heard others mention sugar snakes?). These sugar chains are what determines the trafficking of protein molecules within cells as well as within the body, and their survival.

·Altered glycosylation is a universal feature of malignancy. The changes are very selective and some of these changes are known to directly control invasion and metastasis.


The following information is directly from Wikipedia and the link will follow. I chose to directly paste this within this text for better information to all than what I myself can relay. I tried to pick out the terms many might not be able to define in order to really understand the significance of my starting this thread. I didn’t define all the terms, but only the ones in which I thought were significant or relevant to my own train of thought, if there are any that remain undefined to anyone, I apologize.

Glycosylation is the enzymatic process that links saccharides to produce glycans, attached to proteins, lipids, or other organic molecules. This enzymatic process produces one of the fundamental biopolymers found in cells (along with DNA, RNA, and proteins). Glycosylation is a form of co-translational and post-translational modification. Glycans serve a variety of structural and functional roles in membrane and secreted proteins. The majority of proteins synthesized in the rough ER undergo glycosylation. It is an enzyme-directed site-specific process, as opposed to the non-enzymatic chemical reaction of glycation. Glycosylation is also present in the cytoplasm and nucleus as the O-GlcNAc modification. Five classes of glycans are produced: N-linked glycans attached to a nitrogen of asparagine or arginine side chains, O-linked glycans attached to the hydroxy oxygen of serine, threonine, tyrosine, hydroxylysine, or hydroxyproline side chains, or to oxygens on lipids such as ceramide; phospho-glycans linked through the phosphate of a phospho-serine; C-linked glycans, a rare form of glycosylation where a sugar is added to a carbon on a tryptophan side chain, and glypiation which is the addition of a GPI anchor which links proteins to lipids through glycan linkages.

In glycosylation the polysaccharide chains attached to the target proteins serve various functions. For instance, some proteins do not fold correctly unless they are glycosylated first. Also, polysaccharides linked at the amide nitrogen of asparagine in the protein confer stability on some secreted glycoproteins. Experiments have shown that glycosylation in this case is not a strict requirement for proper folding, but the unglycosylated protein degrades quickly. Glycosylation may play a role in cell-cell adhesion (a mechanism employed by cells of the immune system), as well.

Glycosylation - Wikipedia, the free encyclopedia

[fritolay66]

Here are some of the defined terms I thought were pertinent for this discussion.

Carbohydrates or saccharides are the most abundant of the four major classes of biomolecules. They fill numerous roles in living things, such as the storage and transport of energy (e.g., starch, glycogen) and structural components (e.g., cellulose in plants and chitin in arthropods). In addition, carbohydrates and their derivatives play major roles in the working process of the immune system, fertilization, pathogenesis, blood clotting, and development.

Carbohydrate - Wikipedia, the free encyclopedia

The term glycan refers to a polysaccharide or oligosaccharide. Glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan. Glycans usually consist solely of
O-glycosidiclinkages of monosaccharides. For example, cellulose is a glycan (or more specifically a glucan) composed of beta-1,4-linked D-glucose, and chitin is a glycan composed of beta-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo or heteropolymers of monosaccharide residues, and can be linear or branched.

Glycan - Wikipedia, the free encyclopedia

Biopolymers are polymers produced by living organisms. Cellulose and starch, proteins and peptides, and DNA and RNA are all examples of biopolymers, in which the monomeric units or linkages are respectively sugars, amino acids, and nucleotides.
Cellulose is both the most common biopolymer and the most common organic compound on Earth. About 33 percent of all plant matter is cellulose (the cellulose content of cotton is 90 percent and that of wood is 50 percent).

Many biopolymers spontaneously fold into characteristic compact shapes (see also protein folding as well as secondary structure and tertiary structure), which determine their biological functions and depend in a complicated way on their primary structures. The primary structure is equivalent to specifying the sequence of its cellular subunits. Secondary structures reflect general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids (DNA/RNA). It does not, however, describe specific atomic positions in three-dimensional space, which are considered to be tertiary structure.

Biopolymer - Wikipedia, the free encyclopedia

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching to it other biochemical functional groups such as acetate, phosphate, various lipids and carbohydrates, by changing the chemical nature of an amino acid (e.g. citrullination) or by making structural changes, like the formation of disulfide bridges.
Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Protein - Wikipedia, the free encyclopedia

[fritolay66]

Ceramides are a family of lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of cells. They are one of the component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. For years, it was assumed that ceramides and other sphingolipids found in the bilayer cell membrane were purely structural elements. This is now known to be not completely true. Perhaps one of the most fascinating aspects of ceramide is that it can act as a signaling molecule. The most well-known functions of ceramides as cellular signals include regulating the differentiation, proliferation, programmed cell death (PCD), and apoptosis (Type I PCD) of cells.

Ceramide - Wikipedia, the free encyclopedia

The salvage pathway

Constitutive degradation of sphingolipids and glycosphingolipids takes place in the acidic subcellular compartments, the late endosomes and the lysosomes. In case of glycosphingolipids, exohydrolases, acting at acidic pH optima, cause the stepwise release of monosaccharide units from the end of the oligosaccharide chains one after the other leading to the generation of ceramide whereas sphingomyelin is converted to ceramide by acid sphingomyelinase.

Ceramide can be further hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to leave the lysosome in contrast to ceramide. The long-chain sphingoid bases released from the lysosome may then re-enter pathways for synthesis of ceramide and/or sphingosine-1-phosphate. The salvage pathway re-utilizes long-chain sphingoid bases to form ceramide through the action of ceramide synthase. Thus, ceramide synthase family members probably trap free sphingosine released from the lysosome at the surface of the endoplasmic reticulum or in endoplasmic reticulum-associated membranes.

It should also be noted that the salvage pathway has been estimated to contribute from 50% to 90% of sphingolipid biosynthesis.

Ceramide - Wikipedia, the free encyclopedia

Apoptosis

One of the most studied roles of ceramide pertains to its function as a proapoptotic molecule. Apoptosis, a form of programmed cell death, is essential for the maintenance of normal cellular homeostasis and is an important physiological response to many forms of cellular stress.

Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents including ionizing radiation, UV light, TNF-alpha, and chemotherapeutic agent. This suggests a role for ceramide in the biological responses of all these agents. Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the “tumor suppressor lipid” . Several studies have attempted to define further the specific role of ceramide in the events of cell death and some evidence suggests ceramide functions upstream of the mitochondria in inducing apoptosis. However, owing to the conflicting and variable nature of studies into the role of ceramide in apoptosis, the mechanism by which this lipid regulates apoptosis remains elusive.

Substances known to induce ceramide generation:

TNF-alpha
Fas ligand
Endotoxin
Chemotherapeutic agents
1,25 dihydroxy vitamin D
gamma interferon
Heat (perhaps this may include infrared)
Ionizing radiation
Ceramidase Inhibitors

It is interesting to note that the substances that can cause ceramide to be generated tend to be stress signals that can cause the cells to go into programmed cell death. Ceramide thus acts as an intermediary signal that connects the external signal to the internal metabolism of the cells.

Ceramide - Wikipedia, the free encyclopedia

Please see the links in Wikipedia for mor info on N and O linked glycosylation as it is very pertitent to this discussion. I chose not to include it here because it is a bit more indepth and the length of this post makes me sleepy even trying to compose and edit it. Although I found the following under another linked glycosylation process besides the N and O, in my train of thought I found it interesting to include here as it has been discussed so extensively precviously on many Morgellons forums. It grabs my attention during a head nod doze due to the length of what I have already posted here…..zzzz

[fritolay66]

Phospho-Serine Glycosylation

Xylose, fucose, mannose, and GlcNAc phospho-serine glycans have been reported in the literature. Fucose and GlcNAc have been found only in Dictyostelium, mannose in Leishmania mexicana, and xylose in Trypanosoma cruzi.

Glycosylation - Wikipedia, the free encyclopedia


Tyrosine

Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid. The word "tyrosine" is from the Greek tyros, meaning cheese.

Functions

Aside from being a proteogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes. It functions as a receiver of phosphate groups that are transferred by way of protein kinases (so-called receptor tyrosine kinases). Phosphorylation of the hydroxyl group changes the activity of the target protein.

Tyrosine, which can be synthesized in the body from phenylalanine, is found in many high protein food products such as soy products, chicken, turkey, fish, peanuts, almonds, avocados, bananas, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds, and sesame seeds. Tyrosine can also be obtained through supplementation. My thoughts on this specifically relate to the use of some posters of bannanas, milk, yogurt, pumpkin, and sesame oil on their lesions and swear it helps. Hmmm….istead of the chitinase, what if it is the tyrosine?

Mammals synthesize tyrosine from the essential amino acid phenylalanine (phe), which is derived from food. The conversion of phe to tyr is catalyzed by the enzyme phenylalanine hydroxylase, a monooxygenase. This enzyme catalyzes the reaction causing the addition of an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine.

Catecholamine hormones ie, epinephrine and nor-epinephrine involved in the fight or flight response are produced from tyrosine metabolism. We know continued stress which induces these hormones results in the long term stimulation for the failure of the adrenal glands. Adrenal Exhaustion. I feel this is pertinent because long term stress and the immune system stress would most definitely contribute to Adrenal exhaustion at the very least.

Phosphorylation and sulphation

Some of the tyrosine residues can be tagged with a phosphate group (phosphorylated) by protein kinases. (In its phosphorylated state, it is referred to as phosphotyrosin). Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine.


Precursor to neurotransmitters and hormones

In dopaminergic cells meaning cells in the brain relating to dopamine neurotransmitters, tyrosine is converted to levodopa by the enzyme tyrosine hydroxylase (TH). TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitter dopamine. In addition, in the adrenal medulla, tyrosine is converted into the catecholamine hormones norepinephrine (noradrenaline), and epinephrine.

The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid also are derived from tyrosine. It is also my understanding that many of us suffering from Morgellons also developed hypothyroidism, whether confirmed by lab or not. I am beginning to find many are T3 deficient by word of mouth if that may be important to any.

Tyrosine is also the precursor to the pigment melanin.

Tyrosine - Wikipedia, the free encyclopedia

[fritolay66]

Melanin in humans

In humans, melanin is the primary determinant of human skin color and also found in hair, the pigmented tissue underlying the iris, the medulla and zona reticularis of the adrenal gland, the stria vascularis of the inner ear, and in pigment-bearing neurons within areas of the brain stem, such as the locus ceruleus and the substantia nigra. Now hear is an interesting thought, did you happen to notice the locations of melanin!! They correlate IMHO to everywhere most Morgellons sufferers manifest symptoms.

Dermal melanin is produced by melanocytes, which are found in the stratum basale of the epidermis. Although human beings generally possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism.

Because melanin is an aggregate of smaller component molecules, there are a number of different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism. I am wondering if Eumelanin is what is happening with my hypopigmented scarring, more similar to vitilgo than porphyria. Perhaps it’s the other way around or maybe even all three. I know a lot of us suffer from hypopigmentation, and although I can’t specifically say what is causing Morgellons in all of us, I am rather trying to define what I think may be happening in my own case from my personal history more so than others.

Eumelanin polymers have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymers; recent research into the electrical properties of eumelanin, however, has indicated that it may consist of more basic oligomers adhering to one another by some other mechanism. Thus, the precise nature of eumelanin's molecular structure is once again the object of study. Eumelanin is found in hair and skin, and colors hair grey, black, yellow, and brown. In humans, it is more abundant in peoples with dark skin. There are two different types of eumelanin, which are distinguished from each other by their pattern of polymer bonds. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is in mostly non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans. A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.

Pheomelanin is also found in hair and skin and is both in lighter skinned humans and darker skinned humans. In general women have more pheomelanin than men, and thus women's skin is generally redder than men's. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hair. Pheomelanin is particularly concentrated in the lips, nipples, glans of the penis, and vagina. Pheomelanin also may become carcinogenic when exposed to the ultraviolet rays of the sun. Chemically, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine units which are produced instead of DHI and DHICA when the amino acid L-cysteine is present.

Neuromelanin is the dark pigment present in pigment bearing neurons of four deep brain nuclei: the substantia nigra (in Latin, literally "black substance") - Pars Compacta part, the locus ceruleus ("blue spot"), the dorsal motor nucleus of the vagus nerve (cranial nerve X), and the median raphe nucleus of the pons. Both the substantia nigra and locus ceruleus can be easily identified grossly at the time of autopsy due to their dark pigmentation. In humans, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood. Although the functional nature of neuromelanin is unknown in the brain, it may be a byproduct of the synthesis of monoamine neurotransmitters for which the pigmented neurons are the only source. The loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease there is massive loss of dopamine producing pigmented neurons in the substantia nigra. A common finding in advanced Alzheimer's disease is almost complete loss of the norepinephrine producing pigmented neurons of the locus ceruleus. I know of one whom has shared their MRI scans results and she said they were showing lesions within the brain. I don’t remember if Alzheimer’s patients also show this, perhaps it’s a PET scan I am thinking of?

Melanin in other organisms

Melanins have very diverse roles and functions in various organisms. A form of melanin makes up the ink used by many cephalopods (see cephalopod ink) as a defence mechanism against predators. Melanins also protect microorganisms, such as bacteria and fungi, against stresses that involve cell damage by solar UV radiation or generation of reactive oxygen species. These include high temperature as well as chemical (e.g. heavy metals and oxidizing agents), and biochemical (e.g., host defenses against invading microbes) stresses. Therefore, in many pathogenic microbes (for example, in Cryptococcus neoformans, a fungus) melanins appear to play important roles in virulence and pathogenicity by protecting the microbe against immune responses of its host. A potentially novel role of melanin as a photosynthetic pigment in some fungi, enabling them to capture gamma rays and harness its energy for growth has recently been described. (See radiotrophic fungus) In invertebrates, a major aspect of the innate immune defense system against invading pathogens involves melanin. Within minutes after infection, the microbe is encapsulated within melanin (melanization), and the generation of free radical byproducts during the formation of this capsule is thought to aid in their killing.

[fritolay66]

Biosynthetic pathways

The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed by tyrosinase:

Tyrosine → DOPA→ dopaquinone

Dopaquinone can combine with cysteine by two pathways to benzothiazines and pheomelanins

Dopaquinone + cysteine → 5-S-cysteinyldopa → benzothiazine intermediate → pheomelanin
Dopaquinone + cysteine → 2-S-cysteinyldopa → benzothiazine intermediate → pheomelanin

Alternatively, dopaquinone can be converted to leucodopachrome and follow two more pathways to the eumelanins

Dopaquinone → leucodopachrome → dopachrome → 5,6-dihydroxyindole-2-carboxylic acid → quinone → eumelanin
Dopaquinone → leucodopachrome → dopachrome → 5,6-dihydroxyindole → quinone → eumelanin

Microscopic appearance

Under the microscope melanin is brown, non-refractile and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments which are larger, chunky and refractile and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach.


Melanin in genetic disorders and disease states

Melanin deficiency has been connected for some time with various genetic abnormalities and disease states.

There are approximately ten different types of oculocutaneous albinism, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of black African descent. It is an autosomal recessive disorder characterized by a congenital reduction or absence of melanin pigment in the skin, hair and eyes. The estimated frequency of OCA2 among African-Americans is 1 in 10,000, which contrasts with a frequency of 1 in 36,000 in white Americans.[9] In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000. Another form of Albinism, the "yellow oculocutaneous albinism", appears to be more prevalent among the Amish, who are of primarily Swiss and German ancestry. People with this IB variant of the disorder commonly have white hair and skin at birth, but rapidly develop normal skin pigmentation in infancy.

Ocular albinism affects not only eye pigmentation, but visual acuity, as well. People with albinism typically test poorly, within the 20/60 to 20/400 range. Additionally, two forms of albinism, with approximately 1 in 2700 most prevalent among people of Puerto Rican origin, are associated with mortality beyond melanoma-related deaths.

Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease (pulmonary fibrosis), inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.

The role that melanin deficiency plays in such disorders remains under study.

The connection between albinism and deafness has been well known, though poorly understood, for more than a century and a half. In his 1859 treatise On the Origin of Species, Charles Darwin observed that "cats which are entirely white and have blue eyes are generally deaf". In humans, hypopigmentation and deafness occur together in the rare Waardenburg's syndrome, predominantly observed among the Hopi in North America. The incidence of albinism in Hopi Indians has been estimated as approximately 1 in 200 individuals. Interestingly, similar patterns of albinism and deafness have been found in other mammals, including dogs and rodents. However, a lack of melanin per se does not appear to be directly responsible for deafness associated with hypopigmentation, as most individuals lacking the enzymes required to synthesize melanin have normal auditory function. Instead the absence of melanocytes in the stria vascularis of the inner ear results in cochlear impairment,[14] though why this is not fully understood. It may be that melanin, the best sound absorbing material known, plays some protective function. Alternately, melanin may affect development, as Darwin suggests.

In Parkinson's disease, a disorder that affects neuromotor functioning, there is decreased neuromelanin in the substantia nigra as consequence of specific dropping out of dopaminergic pigmented neurons. This results in diminished dopamine synthesis. While no correlation between race and the level of neuromelanin in the substantia nigra has been reported, the significantly lower incidence of Parkinson's in blacks than in whites has "prompt[ed] some to suggest that cutaneous melanin might somehow serve to protect the neuromelanin in substantia nigra from external toxins.

In addition to melanin deficiency, the molecular weight of the melanin polymer may be decreased due to various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal matrix proteins, changes in pH or in local concentrations of metal ions. A decreased molecular weight or a decrease in the degree of polymerization of ocular melanin has been proposed to turn the normally anti-oxidant polymer into a pro-oxidant. In its pro-oxidant state, melanin has been suggested to be involved in the causation and progression of macular degeneration and melanoma.

Higher eumelanin levels also can be a disadvantage, however, beyond a higher disposition toward vitamin D deficiency. Dark skin is a complicating factor in the laser removal of port-wine stains. Effective in treating white skin, lasers generally are less successful in removing port-wine stains in people of Asian or African descent. Higher concentrations of melanin in darker-skinned individuals simply diffuse and absorb the laser radiation, inhibiting light absorption by the targeted tissue. Melanin similarly can complicate laser treatment of other dermatological conditions in people with darker skin.

[fritolay66]

Freckles and moles are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin. Here is my thought on this. If the invading pathogen utilizes melanin as well, then wherever it invades the skin is where we tend to develop our freakles. Just a thought, it has been very similar to my own experience and that of watching my sons skin over the last couple of years.

Nicotine has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or its irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals. Well no wonder it is so hard to quit smoking.

Melanin and human adaptation

Melanocytes insert granules of melanin into specialized cellular vesicles called melanosomes. These are then transferred into the other skin cells of the human epidermis. The melanosomes in each recipient cell accumulate atop the cell nucleus, where they protect the nuclear DNA from mutations caused by the ionizing radiation of the sun's ultraviolet rays. People whose ancestors lived for long periods in the regions of the globe near the equator generally have larger quantities of eumelanin in their skins. This makes their skins brown or black and protects them against high levels of exposure to the sun, which more frequently results in melanomas in lighter skinned people.

With humans, exposure to sunlight stimulates the skin to produce vitamin D. Because high levels of cutaneous melanin act as a natural sun screen, dark skin can be a risk factor for vitamin D deficiency in regions of the Earth known as cool temperate zones; i.e. above 36 degrees latitude in the Northern hemisphere and below 36 degrees in the Southern hemisphere. As a result of this, health authorities in Canada and the USA have issued recommendations for people with darker complexions (including people of southern European descent) to consume between 1000-2000 IU (International Units) of vitamin D, daily, through Autumn to Spring.

Melanin in the eyes, in the iris and choroid, helps protect them from ultraviolet and high-frequency visible light; people with gray, blue, and green eyes are more at risk for sun-related eye problems. Further, the ocular lens yellows with age, providing added protection. However, the lens also becomes more rigid with age, losing most of its accommodation—the ability to change shape to focus from far to near—a detriment due probably to protein crosslinking caused by UV exposure.

Recent research by J.D. Simon et al. suggests that melanin may serve a protective role other than photoprotection. Melanin is able to effectively ligate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). It may thus serve to sequester potentially toxic metal ions, protecting the rest of the cell. This hypothesis is supported by the fact that the loss of neuromelanin observed in Parkinson's disease is accompanied by an increase in iron levels in the brain.

I also feel this may be why some of us are generating metal like paticles from our skin.

Physical properties and technological applications

I thought it interesting and chose to also include this little tidbit.

Melanins, in the synthetic sense, are "rigid-backbone" conductive polymers composed of polyacetylene, polypyrrole, and polyaniline "Blacks" and their mixed copolymers. The simplest melanin is polyacetylene, and some fungal melanins are pure polyacetylene.

Melanin - Wikipedia, the free encyclopedia

[fritolay66]

Other little tidbits:

In melanocytes, melanosomes (vesicles containing the pigment melanin) are transported on microtubules. They are then bound by Rab27A which recruits Slac2-a and myosin Va. This complex then transfers the melanosomes from the microtubules to actin filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation.

However, these three proteins do not work together in other cells and Rab27A effectors may be 'mix and match' For example the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cells (something that also depends on vesicle transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A.

Griscelli syndrome - Wikipedia, the free encyclopedia

I found the following syndromes in relation to the train of thought I was pursuing in this post and perhaps future discussion may be warranted.

Griscelli syndrome
Chediak-Higashi syndrome
Elejalde syndrome
Hermansky-Pudlak syndrome
Disorders of neutrophilic function such as chronic granulomatous disease of childhood (CGC), myeloperoxidase deficiency, hyper-IgE syndrome and Wiskott-Aldrich syndrome.

So in summary, my train of thought originally started with the hypopigmentation of my skin in which the dermis is composed of melanocytes. Within the body of this text, I tried to cover the pertinent verified or hypothesized functions of the melanocytes. I also established a connection of human melanin and that of other species. And also the hypothesized correlation of Morgellons manifest in myself and the deposition of melanin or lack thereof in my own skin.

Melanin is synthesized from the amino acid tyrosine, which is synthesized from phenylalanine. Glycosylation of tyrosine is an n-linked process. Through this work, I have become aware of phorphorlyation as being the primary pathway for tyrosine and will follow up with phorphorlyation as soon as I can. The sulfation pathway I also believe to be pertinent here due to my own experiences and ditto there too. If anybody has more time than I, feel free to add to this.

I felt it easier to understand my train of thought with my post in reverse order of my train of thought. Basics before the hypothesis type of thing. I hope I have made the right decision.

Again, this post is only a working hypothesis to what may correlate my symptoms with the disease Morgellons. I welcome the feedback of others, as symptoms do vary and any head more than one is better.

I have been working on this post since talking with you TC. I am damn tired of it by now, and sure apologize for the length but I felt it needed to be in one piece, uninterrupted. Who knows, could be nothing at all, but I was wondering if anyone else had similar thoughts?

Frito

[sarothra]

I haven't gone through all of your writings yet, but I noticed you said you had HYPOpigmentation. In my case I exhibit areas of HYPERpigmentation. I am very light skinned. Are you dark skinned or light skinned? Melanin being of issue here.

thanks.

sar