By Abigail Shields, Year 12
Molecules have a great impact on biological systems, with some able to halt life at a cellular level. Some of these compounds enter the system without detection, subtly interfering with critical biochemical pathways, while others work rapidly to halt critical cellular processes. In this article, we shall look at three of the most notorious poisons: arsenic, cyanide, and thallium. Specifically, their chemistry and how it affects systems to lead to their fatality.
Arsenic is a metalloid with no odour and no colour, which disrupts metabolism in cells by interfering with enzymes necessary to produce energy. The arsenite form of arsenic is attracted to thiol (-SH) groups in lipoic acid, which is part of the pyruvate dehydrogenase enzyme complex, thereby preventing this enzyme from converting pyruvate into Acetyl-CoA and thereby preventing mitochondrial production of ATP. The arsenate form of arsenic is similar in structure to inorganic phosphate and is incorporated into the glycolytic pathway, where it is part of an unstable intermediate called 1-arseno-3-phosphoglycerate, which spontaneously hydrolyses and thereby prevents the production of ATP. The ability of arsenic to masquerade as naturally occurring molecules has allowed it to evade detection in the bloodstream and has made it both a deadly poison and a medicine. Perhaps the most famous use of arsenic as a poison was during the Victorian era, when it was used to murder political opponents and even members of one’s own family. For example, the infamous “Acid Bath Murderer” Thomas Neill Cream, who is purported to have poisoned his victims with arsenic during the 1890s.
Similarly, Cyanide works through immediate and direct disruption of respiration. It binds very securely to cytochrome c oxidase, which is part of the mitochondrial transport chain. The binding of Cyanide to this enzyme stops the transport of electrons to oxygen and hence stops oxidative phosphorylation, thereby ending respiration. The cells are unable to use oxygen, despite the fact that they are still breathing and exhaling through the lungs. This is an example of how a small molecule can cause the collapse of life-sustaining processes. Cyanide has long been infamous in history as being used atrociously by Nazi Germany during World War II, as part of gas chambers using potassium cyanide (Zyklon B), causing immediate and catastrophic cellular oxygen depletion.
Thallium, being a heavy metal, works on the principle of molecular mimicry, utilising its similarity to potassium ions (K+) to gain access into the body’s cells, thereby disrupting the ionic balance critical for membrane potential, nerve impulses, and the activity of enzymes. Thallium (TI+) gains access into the cells via voltage-gated and leak potassium channels. Once inside the cells, thallium interferes with protein synthesis, binds to sulfhydryl groups on enzymes, and affects structural proteins like keratin, thereby causing neurological, gastrointestinal, and characteristic baldness, the hallmark of thallium poisoning. Thallium compounds were used as medicines in the early 1900s to treat infections like syphilis, gonorrhoea, and tuberculosis, due to their antimicrobial properties. However, soon the systemic toxicity, which included organ failure, neuropathy, and the cumulative effects of poisoning with a heavy metal, couldn’t be ignored, and thallium compounds were withdrawn as medicines. Thallium poisoning demonstrates how the replacement of an important ion with one that has similar properties and reactivity can compromise the biochemistry and structure of the body’s cells, ultimately leading to death.
Works Cited
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