Wednesday, December 12, 2012

A Gift Worth Its Weight In Gold

Biology concepts – toxicity, trace elements

Say hello to the Holterman nugget of New South
Wales, Australia, supposedly the largest gold
nugget ever found. Strictly speaking, it isn’t a nugget,
but rather a huge vein of gold in a piece of quartz.
And Bernhardt didn’t find by himself, but he was a
shameless media hound and built himself a legend.
In 2nd century Rome, practitioners of Mithraism, a popular pagan religion of the time, had a feast on December 25 to celebrate the god Mithras, the “Invincible Sun.” This also coincided with other feasts for Saturn and the winter solstice. People gave gifts to one another during these holiday celebrations. This practice of gift giving was adopted by Christians when the pagan and Christian traditions were merged, as they often were.

Today, Christmas presents are most often associated with the gifts of the three kings who came to see the baby wrapped in swaddling clothes (although by the time they arrived, Jesus was already a toddler – camels will never be confused with jet planes). Their gifts were gold – a gift for a king, frankincense – a gift for a priest, and myrrh – a gift for one who was to die (used in burial rights).

These three gifts are not exempt from our search for biologic exceptions and amazement. In terms of biology, they are indeed gifts.  This week we will talk about gold, with the others to follow on successive posts, like the ghosts of Christmas past, present, and future.

At December 2012 prices, a 150 lb (69 kg) person has about 37 cents worth of gold in his/her body, excluding any dental work. Hardly worth trying to harvest, but nice to know you’re worth more than you thought. How did the gold get there and is it doing anything?

Living organisms rely on small amounts of some metals and other elements in order to carry out their metabolic reactions. As such, these elements that are needed in small amounts are called trace elements. Examples of important trace elements include selenium, iron, copper, iodine, and zinc. Zinc is probably the king of the trace elements, as it is used in over 200 different reactions in mammalian physiology.

Copper is used in many biochemical pathways,
and it is showing promise as an anti-inflammatory
agent. But NO! people - you can’t get the anti-
inflammatory effects by wearing the copper
bracelets or copper-impregnated compression
wear! On the other hand, copper impregnated
clothes are antimicrobial.
Zinc works to control what genes are activated to make proteins (zinc finger transcription factors), as well as DNA and RNA production and destruction. It is stored in the brain to control just how active some neurons become when stimulated, and plays an important role in neural plasticity – the reordering of neuron connections after experiences and sleep, you may know it as learning and memory. Make sure you take your zinc before studying for that big test!

Because you need only a “trace” of these substances to maintain growth, development and health, they are also called micronutrients. Their functions can be quite diverse. Iron is the oxygen carrier in hemoglobin, but you only need a trace in your diet because you are so good at preserving what you already have. Selenium is contained in a non-traditional amino acid called selenocysteine, which is important for antioxidant proteins (selenium replaces sulphur in the traditional cysteine).

The biologic rule is that gold is not a trace element! Supposedly, no living organism uses gold in its physiology, but you know there has to be an exception. In 2002, Russian scientists investigating a membrane bound enzyme of the aurophilic (au = gold, and philic = loving) bacteria, Micrococcus luteus, showed that the enzyme contained gold in its active site (the area that binds the molecule to be chemical reacted). The gold was important for converting methane to methanol, giving the bacteria a way to produce energy when traditional food sources were scarce.

But we, and presumably ever other organism don’t have this system, so why is there gold in our body? It turns out that we have many things in our body that we don’t use, they just accumulate, things like lead, mercury, cobalt, arsenic. Some are toxic at low levels and some are useful unless we get too much of them. We have discussed the problems associated with having too much iron, and copper excess can be toxic as well. We said zinc is important for many reactions, but too much zinc can hinder copper absorption and you can end up with a copper deficiency. This is just as dangerous as copper excess.

The liver is the site of much detoxification in the body.
Two systems are at work, one to break down or modify
fat soluble toxins, and the other to prepare them and
water soluble toxins for elimination in the bile or urine.
Toxic heavy metals often just get stored in the liver and
cause damage later.
If the element itself or amount of the element is toxic, then we have to get rid of some; this is the job of the liver. In some cases even gold can be toxic; as we accumulate more and more gold in the liver and kidney, it can disrupt their functions. Poor liver and/or kidney function – you die. The classic form of toxic gold found in nature is called gold chloride or “liquid gold,” which causes organ damage in humans and severe toxic effects in other organisms, but there is an exception.

A microbiologist and a professor of electronic art at Michigan State University have worked with a bacterium that can withstand gold chloride levels that would kill every other known organism. They found that Cupriavidus metallidurans was hundreds of time more resistant to gold chloride than any other organism.

C. metallidurans takes in the gold chloride and processes it to pure 24 karat gold, and then deposits it in a thin layer as part of the community of proteins and insoluble products that the bacteria builds around its colony. These organized layer of proteins, lipids and carbohydrates are called biofilms, and are being recognized as very important in bacteria ecology and pathology. In the case of C. metallidurans, the biofilm is intrinsically valuable to Wall Street.

Other organisms accumulate gold as well – bacteria, fungi, algae, fish, etc., but as does everything else in biology, it starts with the bacteria. It turns out that some bacteria excrete high levels of acidic amino acids – aspartate and glutamate (ate means acid). Yes, amino acids that are used to build proteins are organic acids, hence the name.

To dissolve gold out of powdered and broken rock,
many mines like this one in Brazil spray the ore with
sodium cyanide in water. They collect the runoff and
precipitate out the purer gold. I guess they don’t worry
about all the living things contaminated with the
cyanide.
The bacterium Chromobacterium violaceum actually makes and excretes cyanide. Cyanide binds stably to gold and silver, so it is used in gold mining to bind and concentrate very fine gold particles in rocks. Then the gold can be collected and precipitated. These examples show that if gold is in the immediate environment of these various organisms, it can be dissolved by the organic molecules and taken up by the bacteria when they feed.

Once gold is consumed and stored by the bacteria, it enters the food chain; millions of organisms feed on bacteria, and millions of organisms feed on the feeders, and so on. Eventually, we end up eating a little gold as well. This is similar to how fish that ingest food and swim in water contaminated by mercury runoff can end up increasing the human levels of mercury – the difference is that mercury is much more toxic than gold.

The accumulation of gold in sedentary organisms may provide someone with a gold rush. A 2010 study showed that the saprobic fungi (those that feed on decaying material) around an existing gold mine contain much higher levels of gold than ectomycorrhizal fungi (those that are parasitic) in the same area.  The accumulation of gold in soil bacteria and fungi may be able to provide scientifically astute miner with clues as to where they should dig the next mine!

The blue toadstool  (Entoloma hochstetteri) is an
example of a saprobic fungus. It gains all the
nutrients it needs from the soil and from decaying
organic material. Therefore, it picks up and
accumulates other things in the soil – like gold maybe.

 Bacteria may prove even more important to miners. December 2012 evidence indicates bacteria that dissolve and ingest gold in the rocks and soil purify it to some degree. When they form biofilms, the gold becomes insoluble again, and nuggets or flakes are formed. Veins of gold may be due to bacterial byproducts and corpses flowing into cracks in the rocks. Makes you look at your gold ring differently, doesn’t it.

We might be able to thank gold-loving bacteria for more than our jewelry – gold is finding its way into medical treatments and tests these days.  Because gold was rare, pure, inert, and costly, early physicians thought it just had to be good for you. Many remedies had gold incorporated into them, including a popular cure for alcoholism called the Keely cure.

The cure was so widely accepted (and patented by Dr. Keely) that even Theodore Roosevelt himself sent his brother, Elliott, to Dr Keely’s clinic in Dwight, IL to be cured of his addiction. It didn’t work, Elliott drank to the point of depression, and died from injuries that resulted from his jumping from a window.

More recent uses of gold include as an anti-inflammatory agent rheumatoid arthritis, including a compound called aurothiomalate. Just how this works remains a mystery, but a 2010 study in chondrocytes (the cells that make cartilage and are present in joints) showed that this drug down-regulates a signaling enzyme (MAP kinase phosphatase 1) that is important for expression of several inflammatory proteins, including cyclooxygenase, p38 MAP kinase, matrix metalloproteinase-3 and interleukin-6.

The aquatic or semi-aquatic plant Bacopa caroliniania can
be loaded with gold nanoparticles and made to give off
light.  Depending on the energy of the UV light shone on
it, it can glow from green to gold to red. Someday, maybe
our tree lined streets will have natural streetlights.
Gold is finding a home as a treatment in other conditions as well including in cancer, viral infections, and parasitic diseases. But gold is being used most often as a carrier. Because gold is practically inert, nanoparticles of gold can be used to carry drugs to specific targets or to be used as imaging agents to illuminate very small structures.

Most spectacularly, gold may help light a dark world. Plants can now be grown with gold nanoparticles that are small enough to be taken up into the leaf cells. When exposed to UV light, the gold releases energy at a wavelength that stimulates chlorophyll to bioluminesce. The plants actually give off light like natural street lights.

That’s a lot of biology for a hunk of metal used for wedding rings and retirement watches – a way cool gift for any biologist. Next week, the biology of frankincense.

  Nieminen, R., Korhonen, R., Moilanen, T., Clark, A., & Moilanen, E. (2010). Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugs Arthritis & Rheumatism, 62 (6), 1650-1659 DOI: 10.1002/art.27409

 Levchenko, L., Sadkov, A., Lariontseva, N., Koldasheva, E., Shilova, A., & Shilov, A. (2002). Gold helps bacteria to oxidize methane Journal of Inorganic Biochemistry, 88 (3-4), 251-253 DOI: 10.1016/S0162-0134(01)00385-3