Monday, 6 July 2009

Little Sun

If you swallow a vitamin B2 supplement, and the amount is more than your body needs, the vitamin is excreted in the urine. The urine will be a very bright yellow - almost fluorescent. Unfortunately though, for those who like to have fun and want to experiment at home, it doesn't mean your piss will glow in the dark. Vitamin B2 is an easily absorbed micronutrient also known as riboflavin. Like the other B vitamins, it plays a key role in energy metabolism, and is required for the metabolism of fats, ketone bodies, carbohydrates, and proteins. Riboflavin is fluorescent under ultraviolet light.

In animals, riboflavin deficiency results in lack of growth, failure to thrive, and eventual death. Experimental riboflavin deficiency in dogs results in growth failure, weakness, ataxia, and inability to stand. The animals collapse, become comatose, and die. During the deficiency state, dermatitis develops together with hair-loss. Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucus membrane of the gastrointestinal tract.

Aqueous solutions of riboflavin are yellow with a yellowish-green fluorescence. Under the influence of light and alkaline pH riboflavin is transformed into lumiflavin, an inactive compound with a yellowish-green fluorescence. Under acid conditions riboflavin is transformed into another inactive derivative, lumichrome and ribitol. This compound has a blue fluorescence.

Probably the oldest known example of a blue-light response is the growth toward light(phototropism) of various fungal and plant structures; examples include the aerial fruiting bodies (sporangiophores) of the fungi Phycomyces.

Sporangiophores of the fungus Phycomyces are exquisitely sensitive to light, the action of which is to induce a transient increase in the velocity of growth of the sporangiophore. When illumination is asymmetric, the lens properties of the sporangiophore focus the light such that a net growth increase occurs on the side away from the light source; this results in growth toward the light, i.e., photo-tropism. A similar mechanism is probably operative in sporangiophores of the related fungus Pilobolus. Phototropism enables the fruiting bodies of these fungi to grow out from the depths of crevices in order to disperse their spores somewhere other than the present home of the organism. It is thus a tremendously valuable ability for these organisms to have.

Thus both riboflavin and g-carotene are molecules which enjoy wide biological prevalence. Carotenoids, in particular ß-carotene, have long been candidates for the role of photoreceptor for the various blue light-controlled pro-cesses. The main points supporting this candidacy were the presence of carotenoids in the blue light-sensitive organisms, the general similarity of the g-carotene absorption spectrum and the various physiological action spectra, and the fact that carotenoids are closely related to retinal, the molecule already well known as the photoreceptor for vision in animals.

The notion that riboflavin, rather than a carotenoid, might be playing the role of blue-light receptor has had its ups and downs since Galston first raised the point three decades ago. However, over the past ten years the consensus has come to be that riboflavin is probably functioning as the receptor for blue light-mediated physiological responses in most of the organisms that have been studied. One strong argument providing support for a flavin rather than a caro-tenoid photoreceptor is the presence of a band in the long.

Among the many organisms that exhibit physiological responses to blue light there may in fact exist several different blue-light receptors with differing mechanisms of action. Retinal was apparently discovered and put to use by life as a photoreceptor at several independent points in evolution, the results being retinal-based vision in animals and retinal-based energy and sensory phototrans-duction in the Halobacteria. Given the ubiquity of riboflavin among living organisms,it would be far less surprising here than it was for retinal that life would put to use the photochemical properties of this molecule at several independent points in evolution.

Some inks glow faintly (fluoresce) when under an ultraviolet lamp. This is a property of many substances, particularly organic substances and body fluids. When the British Secret Intelligence Service (SSB) discovered that semen made a good invisible ink, Sir George Mansfield Smith-Cumming noted of his agents that "Every man carries his own stylo".

There's a popular urban myth that energy drinks contain the ingredient taurine which comes from bull's semen. Taurine is a lesser known amino acid. Adults can produce sulphur-containing taurine from cysteine with the help of pyridoxine, B6. Taurine functions in electrically active tissues such as the brain and heart to help stabilize cell membranes. While taurine is present in both bull semen and urine, the taurine used in energy drinks such as Red Bull is not taken from these sources. If the story were true - could you imagine the ramifications in trying to gather it?

Most specimens of bull semen are almost white, but during the course of unrelated studies on spermatozoa it was observed that the semen from one particular bull was quite yellow. The colour was confined to the plasma fraction and ultra-violet light produced a green fluorescence similar to that emitted by riboflavin. Other reports have since been noted which suggest that the yellow pigmentation of bull semen may be attributed to riboflavin, and recently eight bulls producing yellow semen have been located, thus permitting a more critical and extensive investigation.

The pigmentation apparently does not affect the fertility of the semen since the bulls were in use at artificial insemination centres and the spermatozoal concentration and morphology were normal.

Riboflavin also helps our bodies make glutathione, a free radical scavenger that’s produced by cells. Some people simply can’t produce glutathione because of an inherited abnormality, and they have a marked increase in cell damage. Red blood cells break down more easily, while white blood cells and nerves are also affected. With more riboflavin to support the production of glutathione, it seems reasonable to assume that people would experience less cellular damage.

Animal research has led some scientists to believe that people who are deficient in riboflavin are more likely to develop cataracts, because glutathione helps to protect the eyes from damage by sunlight.

In one study on animal tissue, researchers found that riboflavin can help protect tissues from damage from oxygen that occurs when blood flow stops, then starts again. That stop-start pattern is exactly what develops when someone has a heart attack or stroke.

"Glutathione is a very interesting, very small molecule that's [produced by the body and] found in every cell," says Gustavo Bounous, MD, director of research and development at Immunotec and a retired professor of surgery at McGill University in Montreal, Canada. "It's the [body's] most important antioxidant because it's within the cell."

Evidence for the important role that glutathione plays in health comes from studies in people who are severely ill.

"If you look in a hospital situation at people who have cancer, AIDS, or other very serious disease, almost invariably they are depleted in glutathione," says Appleton. "The reasons for this are not completely understood, but we do know that glutathione is extremely important for maintaining intracellular health."

Glutathione is a tripeptide. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Tissue and sperm glutathione concentrations can be raised by increased intake of the precursor cysteine, a necessary building block of glutathione. Worthy of note at this stage perhaps, is that glutathione inhibits and blocks tryrosinase, the enzyme responsible for dark melanin pigments.

Glutathione has recently been used as an inhibitor of melanin in the cosmetics industry. In countries like the Philippines, this product is sold as a whitening soap. Glutathione dose dependently inhibit melanin synthesis in the reaction of tyrosinase and L-DOPA. These results indicate that glutathione inhibits the synthesis and agglutination of melanin by interrupting the function of L-DOPA.

With a thiol side chain, cysteine is classified as a hydrophobic amino acid. Because of the high reactivity of this thiol, cysteine is an important structural and functional component of many proteins and enzyme. Due to the ability of thiols to undergo redox reactions, cysteine has anti-oxidant properties.

Cysteine is a sulfur-containing amino acid. Cysteine is present in keratin, the main protein that makes up nails, skin and hair. It aids in the production of collagen and provides elasticity in the skin. Cysteine is important in energy production because it can be converted to the sugar glucose which the body can burn. Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches.

Cysteine is more easily absorbed by the body than cystine, so most supplements contain cysteine rather than cystine. In nature, E.coli bacteria produce cysteine from sugar, salts and trace elements for their own metabolism. At the present time, the cheapest source of material from which food-grade L-cysteine may be purified in high yield is by hydrolysis of human hair.

The basic building block of hair, responsible for 91 percent of its dry weight, is keratin. A strand of hair consists of 3 primary structures: the cuticle (which is the outermost, shingle-like layer); the cortex (the inside of the hair consisting of bundles of protein filaments; and the medula (a soft spongy-like core in the center of the cortex.) The cortex contains densely packed keratin. The inner part of the hair is sometimes referred to as the "pith"

Keratin, a simple protein of albuminoid nature, is the chief constituent of hair, indeed of all epidermal tissue—nails, feathers, horns and hoofs. Keratin is peculiar, in that it has a high sulphur content, the sulphur being present almost entirely in the form of the amino-acid cystine. No other protein is so high in cystine as the keratin of human hair. It would appear,therefore, that the metabolism of sulphur probably plays an important role in the development and growth of these tissues.

As with all other amino acids, the vital role of cysteine is to contribute to the structure of protein, which it does in the form of cystine. Cysteine is in the same class as methionine. When it is exposed to air, cysteine oxidizes to form cystine, which is a dimer of two cysteine molecules joined by a weak disulfide bond. Cystine holds proteins in shape and determines the form and properties of animal and plant proteins.

A decrease in the cystine content of human head hair following moderate bleaching has been found. During hair bleaching the primary consequence of the treatment is oxidation of the melanin. Photochemical degradation of hair proteins occurs primarily near 254 to 350 nm, the primary absorbance region of unpigmented hair. Although several amino acids are degraded by light, the primary degradation occurs at cystine.

Hair pigments function to provide some photochemical protection to hair proteins, especially at lower wavelengths, where both the pigments and the proteins absorb light (254 to 350 nm). Hair pigments accomplish this protection by absorbing and filtering the impinging radiation and subsequently dissipating this energy as heat. However, in the process of protecting the hair proteins from light, the pigments are degraded or bleached.

THE sun can make your hair turn grey, new research shows. The same ultraviolet light in the sun's rays which damages skin can also inflict "genotoxic stress" on the adult stem cells which give hair its colour. Japanese researchers have shown that some types of biological body stress, such as ultraviolet light, some chemicals and ionising radiation, damage our DNA. The "irreparable" DNA damage causes the melanocyte stem cells to change the way thay act.,22606,25623374-5006301,00.html

The color of hair is due to the presence in the cortex of granules of a pigment called melanin, which is formed in special pigment-producing cells (melanocytes) in the hair bulb during the growing phase (anagen) of each hair. The melanin granules lie along the amino acid chains of the proteins, looking under the microscope rather like a string of pearls.

Two types of melanin are produced by melanocytes. Eumelanins are black/brown melanins with high photoprotective properties and pheomelanins are red/yellow sulfur containing pigments that provide no protection against the noxious effects of solar irradiation.

Genes determine hair color by directing the type and amount of pigment that epidermal melanocytes produce. If these cells produce an abundance of melanin, the hair is dark. If an intermediate quantity of pigment is produced, the hair is blond. If no pigment is produced, the hair appears white. A mixture of pigmented and unpigmented hair is usually gray. Another pigment, trichosiderin, is found only in red hair.

The following extract is taken from Harriet Hubbard Ayer’s Beauty Book. Though it contains sound advise "on the sin of dowdiness", I am unsure about the exact science behind Harriet's musings on hair pigments. Hair does contain trace elements of metals but these amount to less than 1%. I've included Harriet's wisdom here because I am absorbed by her name, and her cheeky Victorian bed-side manner. And who knows? Maybe one day we'll find out she was right.

The coloring matter of the hair has been scientifically shown to consist of the mineral ingredients in the pigment of the cells. These minerals change with age and health, and vary in individuals. Very blond hair contains a large proportion of magnesia; iron predominates in black hair; chestnut and browns contain a large amount of sulphur.

When the iron or sulphur pigment fails, the hair becomes gray, and as iron appears to fail earlier than sulphur, black hair is oftener found turning gray in youth than any other color. Sulphur comes next, and the magnesia resists longer than any of the others, for which reason blond hair often retains its youthful beauty and luster far beyond middle age.

The reason the golden hair of little children darkens as they grow older is because the hair pigment changes, the sulphur or iron increasing and becoming more powerful than the magnesia.

Current thinking is that hair pigment plays some role in the incorporation of trace elements and not the other way around. Hair is hydroscopic and the absorption of water is very rapid, enabling liquids (sweat, shampoo, dyes, etc) including ions of trace element pollutants to enter the hair. Some experiments have shown hair to behave, to some extent, as an ion exchanger (Bate 1966).

Trace amounts of metals are needed in the structure of pigments though. Bright red hair contains an iron pigment (trichosiderin) that does not occur in hair of any other colour. There's also copper, which is incorporated into the melanin molecule through the amino acid tyrosine. Tyrosinase, a copper-containing enzyme, converts tyrosine to melanin, which is the pigment that gives hair and skin its color.

Melanin or an associated product in the retinal pigment epithelium (RPE) regulates retinal maturation, because in albino mammals the central retina is underdeveloped and there is a cell specific deficit in the rod population.

Melanin means 'black amino' and is a color pigment composed of a hydrocarbon chain which has various amino (nitrogen-based) compounds attached to it. It is carbon that gives melanin its blackness. Carbon is the organizing molecule that gives melanin its structure. It is carbon that gives melanin the ability to absorb energy and bind with other molecules while retaining stability and coherence. Another element important to the structure of melanin is sulphur.

Sulphur is incorporated into the melanin molecule through the amino compound cysteine. Cysteine is an amino compound that is organized around sulphur, nitrogen, and carbon. This amino acid facilitates melanin’s heat and energy transference. In other words, it allows melanin to create or release heat as is needed for the body. Cysteine also cleanses and purifies melanin by ‘burning off’ toxic elements that have been absorbed within melanin.

Cystine is created when two cystines oxidize and bond together. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the bladder or kidney. Cystine crystals are transparent and hexagonal and their solubility is increased in an alkaline medium. The crystals have a brilliant silvery birefringence when viewed under polarized light.

Cystinosis is a rare genetic disorder that causes an accumulation of cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes. The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal (kidney) epithelial cells.

A symptom of cystinosis is the accumulation of cystine crystals in the eyes, leading to damage to the retina and loss of sight. With the continued build-up of cystine crystals, the cornea becomes opacified, resulting in decreased vision and the need for corneal transplantation in some patients. The deposition of cystine crystals in the cornea causes photophobia (sensitivity to bright light). Patients endure disabled vision, blurring, redness, pain, irritation, and itching in their eyes. The following paragraph is taken from a story about four-year-old Tina, who has been diagnosed with cystinosis:

Cystine crystals are clearly building up in Tina’s eyes, as is evident by her growing sensitivity to sunlight. Bright light causes the eye crystals to act as a prism, causing severe eye pain and discomfort. Eventually, Tina will start on cysteamine eye drops, which will keep her from developing retinopathy, or blindness. The eye drops must be taken every waking hour and sting considerably. They must remain refrigerated at all times. They are not FDA approved, making them difficult to purchase.

I was blown away by Tina's courage. I am starting to appreciate that cystinosis is not simply a problem with the eyes and kidneys. It is something which effects Tina "from head-to-toe". Sadly, cystinosis disrupts Tina's quality of life. Cystinosis, and the treatment of her cystinosis, is something that consumes practically every moment of Tina's life. I have nothing but admiration for Tina, and her parents.

Light sensitivity is usually due to too much light entering the eye, which causes over stimulation of the photoreceptors in the retina and subsequent excessive electric impulses to the optic nerve. This leads to a reflex aversion to light, and discomfort or pain. Some cystinosis patients have been known to display an unusual accompanying reflex - sneezing when exposed to a sudden bright light (photic sneezing). The stimulus might not only be sunlight, but also artificial light, and UV.

The role of intra-orbital trigeminal nerve stimulation was proposed by Katz et al, who found a high incidence of photic sneezing in patients with corneal crystals secondary to nephropathic
cystinosis. They suggested that cystine crystal deposition results in dysfunction of the peripheral branches of the trigeminal nerve, leading to supersensitivity and hence photophobia and photic sneezing.

The theory of parasympathetic generalisation invokes co-activation by one stimulus of neighbouring parasympathetic branches. Light falling on the retina stimulates pupillary constriction (via the third cranial nerve) and lacrimation (via the seventh). A stimulus of
sufficient intensity could generate enough parasympathetic activity to cause nasal congestion and secretions, and stimulate sneezing by an effect on the maxillary branch of the trigeminal nerve.

Patients with infantile cystinosis have hypopigmentation with, for Caucasian subjects, blond hair, blue eyes and a clear skin. However it seems that some patients, in particular African American patients, but also few Caucasian patients have no hypopigmentation. Unfortunately no correlation between cutaneous phenotype, severity of renal disease and genotype has been carried out. The causes of hypopigmentation have not been so far elucidated. In humans, pigmentation results from the synthesis and distribution of melanin in skin, hair bulbs, and eyes.

Hypopigmentation is the loss of skin colour. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin. Hypopigmentation of the skin and hair can result from copper deficiency in humans; the depigmentation associated with chronic excessive molybdenum intake is related to a decreased storage of copper in the liver.

Under the trade name Cystagon, cysteamine is used in the treatment of disorders of cystine excretion. Cysteamine is a cystine-depleting agent. It works by reducing the amount of cystine in the body. Cysteamine was first used in the cold war for radiation treatment. Cysteamine is currently under investigation as a protective agent in radiation therapy. A lot of experiments have been done on mice which reveal that cysteamine has a tendency to protect normal healthy tissue from radiation damage, without protecting the tumour tissue.

It is well known that when cells become hypoxic they become radioresistant. Hypoxia is where the body as a whole, or a region of the body, is deprived of oxygen. Increasing the oxygen concentration above atmospheric levels leads to increased radiation sensitivity in most mammals, and is known as the "oxygen effect".

It has been reported that the intracellular level of cAMP in moderately hypoxic cells markedly increases, therefore the radioresistance of hypoxic cells may, in-part, be related to a rise in cellular cAMP. Cysteamine is known to elevate intracellular levels of cAMP.

Cyclic adenosine monophosphate (cAMP) is a second messenger that is important in many biological processes. Many water soluble hormones do not cross the cell membrane, but instead cause effects within the cell via a second messenger. cAMP is used for intracellular signal transduction, such as transferring the effects of hormones like glucagon and adrenaline, which cannot get through the cell membrane. It is involved in the activation of protein kinases and regulates the effects of adrenaline and glucagon. It also regulates the passage of Ca2+ through ion channels.

A possible mode of action of cysteamine is that it might react with extracellular cystine to form cysteine which then is readily taken up into the cell and transformed into glutathione (gamma-glutamyl-cysteinyl-glycine; GSH)

Glutathione itself is does not enter easily into cells, even when given in large amounts. However, glutathione precursors do enter into cells and have been shown to be effective in the treatment of conditions such as acetaminophen toxicity by preventing significant GSH depletion (Prescott & Critchley, 1983). Examples of GSH precursors include cysteine, N-acetylcysteine, methionine and other sulphur-containing compounds such as cysteamine (Prescott, Park & Proudfoot, 1976).

Glutathione, as you may remember, is an antioxidant which inhibits and blocks tyrosinase, the enzyme responsible for dark melanin pigments. Melanin reduces the penetration of UV radiation through the epidermal layers, and scavenges reactive oxygen species that are generated in the skin on sun exposure. It's a reminder that in the early 19th century, when ultraviolet wavelengths were first being discovered, some knew them as "deoxidizing rays".

A hallmark of sun exposure is increased melanin synthesis by cutaneous melanocytes which protects against photodamage and photocarcinogenesis. Irradiation of human keratinocytes or melanocytes with ultraviolet (UV) rays stimulates the synthesis and releaseof a-melanotropin (a-MSH) and adrenocorticotropic hormone (ACTh), which induce cyclicAMP (cAMP) formation and increase the proliferation and melanogenesis of human melanocytes. We report that stimulation of cAMP formation is obligatory for the melanogenic response of cultured normal human melanocytes to UVB radiation. In the absence of cAMP inducers, UVB radiation inhibited, rather than stimulated, melanogenesis....

...Our results underscore the importance of the CAMP pathway and its physiological inducers in mediating the response of human melanocytes to UV radiation.

Although the entire process of pigment formation involves many complex interactions - the crucial element of the melanogenic pathway is the action of the principal oxidizing enzyme, tyrosinase.

Protection against UV rays is guaranteed by the tanning response in which UV radiation triggers the production of melanin in the melanocytes. These are specialized cells localized in the basal layer of the epidermis that synthesize melanin in organelles called melanosomes. The melanosomes are transferred via dendrites to the neighboring keratinocytes where they generate a protective screen around the cell nucleus.

Two key upstream components of the melanin cascade process are the α-melanocyte-stimulating hormone (α-MSH) and its receptor, the G-protein coupled melanocortin-1 receptor
(MC1R). The expression of their genesis UV-inducible. Binding of α-MSH to MC1R increases the intracellular level of cAMP, which finally leads to an increased expression of the tyrosinase gene that encodes the rate-limiting enzyme in the synthesis of melanin.

[Researchers] showed Mc1r-deficient mice (i.e., mice analogous to red-haired humans) to be incapable of tanning in response to ultraviolet radiation (UVR). When these mice were exposed to topical forskolin, a compound that permeates cells and increases intracellular cAMP levels, their skin darkened dramatically (which correlates with profound eumelanin production). Thus, when nature cannot generate cAMP in response to UVR because of defects in MSH signaling, compounds that directly increase cAMP offer a pharmacologic approach to eumelanization.

In vivo, Phycomyces shows a positive growth response to blue light. It is demonstrated that blue light can increase the chitin synthetase activity in vitro. The following extract also shows a marked effect upon cAMP levels by blue light:

At the University of Florida, I initiated several lines of biochemical and biochemical genetic investigations of Phycomyces. We studied the chemistry of the cell wall and the enzymology of chitinase and chitin synthetase to try to obtain a clue about the regulation of cell growth...

...We also showed that cAMP and cGMP levels were quickly changed by blue light.

The following extract is taken from a paper entitled the "History of Ultraviolet Photobiology". It was written by Philip E. Hockberger. I thought the paper to be a fantastic read. Below, a few paragraphs taken from the paper seem to tie together the elements that I've drawn out in this post. I feel like it's gone full circle. The post was certainly longer than I thought it would be. I am, as yet, unable to draw any real conclusions. I feel like this post needs to be condensed, squashed up like an accordion, and injected into my brain, before I can begin to formalise ideas.

Webb (15) reviewed the literature showing that UVA rays cause lethal and mutagenic effects in microorganisms even in the absence of exogenous photosensitizers. Unlike UVB effects, UVA effects are oxygen-dependent. In 1980, D'Aoust and colleagues (298) showed that flavins are endogenous photosensitizers which underly the damaging effect of visible light in bacteria. Hartman (299) reported that irradiation of E. coli with UV rays (300-400 nm) induced hydrogen peroxide production, a process that probably involves flavins (300).

Curry & Gruen (326) demonstrated positive phototropism to violet-blue light using Phycomyces (fungus). In 1960, Delbrück & Shropshire (327) showed that the action spectrum for phototropism in Phycomyces corresponded to the absorption spectrum of flavinoids.

Most studies of UVA and violet-blue light responses have implicated carotenoids and flavins as molecular photoreceptors. In 1935-37, Castle (332) and Bünning (333) proposed that carotenes were involved in phototropism in the fruiting bodies of Phycomyces and Pilobolus (fungi) and in the coleoptiles of the plant Avena. In 1950, Galston (334) proposed the alternative "flavin hypothesis" in which riboflavin acts as a photosensitizing agent in the photooxidation and stimulation of the growth hormone (auxin) indole acetic acid. Forty years later, Galland (335) reported that flavins are still regarded as the most common photoreceptors in blue light responses, although carotenoids and pterins have been implicated in some cases.

But if I was asked to leave a final thought here today, it would be something about pressure. If I was trying to simplify the above post I might be tempted to say that it all has something to do with pressure.... pressure inside cells .... blood pressure ... aether field pressures.... ????

Many, many thanks:

Chemical and physical behavior of human hair By Clarence R. Robbins
The invertebrates By Richard Stephen Kent Barnes, Peter Calow, Peter Olive
Nutrient requirements of dogs and cats By National Research Council (U.S.). Ad Hoc Committee on Dog and Cat Nutrition, National Research Council
Harley's pediatric ophthalmology By Robison D. Harley, Leonard B. Nelson, Scott E. Olitsky
International review of cytology By Geoffrey Howard Bourne, International Society for Cell Biology
Handbook of radiobiology By Kedar N. Prasad

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