At ordinary temperatures and pressures, it is a liquid metal. More importantly, it is a reactive element. Since it was first isolated, mankind has developed and increasingly vast array of uses for mercury. Over time we have slowly become aware of the dangers of occupational mercury poisoning, but only recently have we deduced some of the actual mechanisms involved. The advances in mercury toxicology have led us full circle: we now know that the real danger for the general public lies in naturally occurring mercury compounds that accumulate in the food chain. This danger presents itself as a chronic, low-level intake of mercury compounds. However, most of our knowledge of mercury poisoning comes from studies of cases of acute poisoning. There is very little known about chronic exposure.
What Forms Does Mercury Exist In? Most people are familiar with mercury in its elemental, liquid state. Liquid mercury can be found right in your home, either in the house's thermostat, or in a thermometer. Amalgams of mercury have been used for metallurgical purposes, and more recently for dental fillings. In fact, you probably have mercury amalgam fillings right in your mouth! Mercury also exists in many forms in nature, both as mercury vapor and in many compounds and minerals. Mercury also exists as monomethylmercury (MeHg). This form of mercury is particularly toxic, as is participates directly in biochemical reactions. MeHg is created both by humans and by the environment. Industry uses MeHg, and in the past there have been poisonings due to industrial discharge. MeHg is also created through biomethylation processes in the environment, and this MeHg bioaccumulates primarily in fish. The greatest source of MeHg is natural biomethylation, and fish consumption is the principal source of MeHg intake for most people.
How do mercury compounds enter the human body? Mercury compounds vapor can enter the body through various pathways, including inhalation of vapor, ingestion, and skin contact. Most of our exposure to elemental mercury comes from inhalation of mercury vapor, while most of our exposure to MeHg comes from ingestion. If we keep in mind that mercury vapor is a nonpolar, monatomic gas, and therefore lipid-soluble, it is easier to follow its journey through the body and to the brain. For example, let's follow the path of inhaled mercury vapor. From the lungs it dissolves in blood plasma, and from there it has access to diffuse into any cell in the body. Once inside a cell, mercury vapor, itself unreactive, is oxidized to the highly toxic mercury (+2) ion. This is also known as divalent mercury. This oxidation process is mediated by the enzyme catalase. Catalase normally functions in a two-step process to remove hydrogen peroxide from cells. However, in the second step of this process, mercury vapor can be oxidized to divalent mercury. Although this seems to be an unfortunate reaction, it helps to protect the brain from mercury exposure. This is because a lot of the mercury vapor we inhale is oxidized by, and trapped in, red blood cells. This keeps most inhaled mercury vapor from ever reaching the brain. However, some elemental mercury vapor does reach the brain, and there it is also oxidized to divalent mercury. This divalent mercury in the brain leads to strange symptoms, including erethism (mad hatterís disease). However, the process by which this happens is still not known. It is believed that divalent mercury attaches to receptors in the brain, but this is only a piece in the puzzle linking mercury in the brain to behavioral symptoms.
What does MeHg do in the human brain? Monomethylmercury (MeHg) is an estimated 100 to 1000 times more toxic (than elemental mercury) to humans. In fact, MeHg seems to specifically target the advanced Central Nervous System (CNS). Until recently, this was a mystery, as the CNS enjoys the protection of the Blood Brain Barrier (BBB). The BBB consists of tightly packed endothelial cells that line the walls of the blood capillaries in the CNS. The key to understanding why MeHg is so toxic is to see that structural similarities in biochemical reactions can lead to active transport of toxins. In the case organisms with a highly advanced CNS, like humans, this active transport can lead a brain accumulation of MeHg. As mentioned before, most of our exposure to MeHg comes from bioaccumulations in fish. When we eat contaminated fish, this ingested MeHg easily passes through the intestines and into the bloodstream. The pathway of MeHg from the bloodstream to the brain is complicated, and we think it is easiest to understand the pathway through a list of the various processes involved:
MeHg in blood plasma can combine with cysteine, forming a compound that is structurally similar to the amino acid methionine
This MeHg-cysteine compound is actively transported into the endothelial cells in the BBB, on the methionine carrier.
A high level of reduced glutathione is maintained in the endothelial cells, and the MeHg switches from a cysteine carrier to a glutathione carrier.
MeHg-glutathione is actively transported out of the endothelial cells and into the brain.
In the brain, the hydrolysis of MeHg-glutathione generates MeHg-cysteine.
This MeHg-cysteine can now enter nerve cells in the brain, where it accumulates. The reason why it accumulates is unknown, but it is known that reduced glutathione levels are low in some neurons. It is thought that this low level of reduced glutathione might allow MeHg-cysteine to remain in the cells, unlike in the endothelial cells. Furthermore, since MeHg-cysteine is structurally similar to the amino acid methionine, it may interfere with protein synthesis in nerve cells. This is especially likely, since methionine is always the first amino acid involved with protein synthesis. However, the exact process is not yet fully understood. The toxicity of MeHg in the developing brain is even more complicated. MeHg has been shown to affect proteins that are involved in the assembly of microtubules in the nerve cell's cytoskeleton. By noting that microtubules are essential for nerve cell division and migration, we see how MeHg can affect brain growth and development. This is why the fetal brain is particularly sensitive to MeHg. Also, the BBB of the fetal brain is about three times more active in amino acid transport, which only makes the MeHg brain concentration rate higher. MeHg also produces subtle changes in the production and secretion of neurotransmitters in the developing brain, which alters brain development in subtle ways. For example, MeHg has been shown to accumulate in astrocyte cells in the developing brain. One role of astrocytes is to regulate levels of the amino acid glutamate in the developing brain. It happens that glutamate is toxic to the developing brain. Since an inhibition of astrocyte cell function will enchance glutamate levels, we can see an indirect path for mercury poisoning in the brain. This is a very complex subject, and very little is known about the exact developmental changes that are expected from MeHg contamination.
How can we detect mercury in the body? The standard methods for determining the concentration of mercury compounds in the body involve urine, blood, and hair samples. The problem with these methods is that they only show a recent history of mercury exposure, whereas mercury is a cumulative toxin. Since these tests cannot account for past exposures, they are only valid indicators of recent, acute exposure. This is part of the reason that there is so little known about chronic, low-level MeHg contamination.
Can we treat mercury poisoning? Unfortunately, by the time symptoms appear, usually the damage is already done. This is complicated by the fact that mercury poisoning is difficult to diagnose. However, when mercury contamination is diagnosed and there is still a concentration of mercury in the body, chelation therapy may help. Chelation therapy involves the formation of a complex of mercury with a chelate ligand. EDTA is such a chelating ligand, and it has been used in the treatment of mercury poisoning. Doses of chelating agents increase the blood and urine concentrations of mercury, and thus help eliminate it from the body.