We live in a toxic world, and most people would agree we have no one to blame but ourselves. After all, as far back as 1981 more than 100,000 industrial chemicals were already registered with the European Inventory of Existing Commercial Chemical Substances. (1) And, with industry busily churning out 150 to 200 new chemicals every year – usually after conducting only the most rudimentary pre-market toxicity testing – it’s easy to understand why our planet is awash in potentially harmful substances.
However, while humankind has done more than all other species combined to defile the only habitable orb within spitting distance, it must be acknowledged that Earth has always been a challenging place to live. Long before Homo sapiens was so much as a cipher on the celestial drawing board, single-celled organisms drifting about in Earth’s primordial environs were contending with deadly gases, noxious chemicals, and hazardous radiation. These simple organisms couldn’t flee from such threats or modify their surroundings to ameliorate them, so they had to develop the metabolic machinery to deal with them.
Take ultraviolet light, for instance. Early in Earth’s history, when the atmosphere was still relatively thin, UV light represented a major deterrent to a cell’s survival and successful reproduction. Some experts believe that microorganisms living in the upper layers of Earth’s ancient seas, where UV light was most intense, used cholecalciferol (vitamin D3) to shield their delicate DNA from the pernicious effects of the sun’s rays. In an elegant example of evolutionary adaptation, early microbes acquired the means to exploit the very entity that could injure their chromosomes – UVB light – to synthesize cholecalciferol. Later, with the arrival of multicellular organisms, vitamin D3 became important in intra- and intercellular signaling. Still later, vitamin D3 assumed additional roles in calcium metabolism, skeletal maintenance and immunity. (2) The metabolic pathway used to manufacture cholecalciferol has persisted through billions of years of evolution.
Oxidation, an inevitable consequence of living in Earth’s atmosphere, is another force that can wreak havoc on a cell’s chromosomes, as well as it enzymes, structural proteins, and other vital components. Unfettered oxidation causes derangements in most biological processes and ultimately leads to cellular death. Paradoxically, oxidation is also the process cells employ for catabolizing carbohydrates, fats, and amino acids to produce adenosine triphosphate (ATP), which is the principal source of energy required by all living cells. Furthermore, oxidation is a necessary step in the neutralization of many toxic substances, as well as the synthesis or activation of a variety of useful ones. Hence, in order to survive a cell must be able to capitalize on the oxidative processes that are beneficial while simultaneously harnessing those that are inherently harmful. As is the case with cholecalciferol synthesis, the metabolic machinery needed to channel the power of oxidation has survived for eons and is strikingly similar in all living organisms. According to the ruminations of the evolutionary biologists, about 3.5 billion years ago an assortment of molecules called cytochromes first appeared in primitive life forms, most likely in prokaryotic bacteria. (3) Cytochromes are a diverse group of proteins that share a common central feature: an iron-containing heme group that allows them to transfer electrons from one molecule to another. Since electron transfer is crucial to the process of oxidation (as well as its inverse operation, reduction), cytochromes have been recruited to perform a multitude of metabolic tasks through the ages. The fundamental importance of cytochromes is reflected in their persistence through millennia of evolution and their presence in all species lines. Cytochrome c, the key to oxidative phosphorylation and ATP production in all aerobic cells, is found in the most primitive as well as the most advanced organisms. Likewise, the cytochrome P450 system (CYP450) is a family of metabolic enzymes found throughout the biosphere; CYP450 enzymes drive the oxidation and hydroxylation reactions that can either detoxify harmful substances or initiate the synthesis of compounds that are critical to life.
Most cells in the human body are endowed with a full contingent of cytochromes, in addition to the genes needed to regenerate these indispensable enzymes. (Red blood cells, which shed their nuclei and organelles during maturation, are the exception; the few cytochrome-like molecules found in red blood cells cannot be renewed and must last for the lifetime of the cell.) Cytochromes are usually closely associated with cellular membranes, which provide an architectural framework that allows a given group of cytochromes to function more efficiently. Cytochrome c – the cytochrome involved in energy production – is primarily located along the inner membranes of mitochondria. (Mitochondria are intracellular organelles where the lion’s share of a cell’s energy is produced.) The CYP450 enzymes, which participate in the metabolism of the astonishing array of substances that enter our bodies each day, are typically linked to a cell’s endoplasmic reticulum, Golgi apparatus and similar structures. Liver cells, which are subjected to higher toxic exposures than other cells, are particularly rich in CYP450 enzymes.
Nearly every foreign substance – whatever we eat, drink, inhale, or absorb through our skin – is a potential substrate for the CYP450 system. Without this protective array of enzymes, our cells would quickly succumb to the direct and indirect effects of the myriad chemicals we encounter as we proceed through life. Indeed, the mere act of consuming a meal (even one composed entirely of organic foods) would overwhelm our cells with an unmanageable burden of toxins. The beauty of the CYP450 system rests in its ability to detoxify such a wide variety of compounds, including many that are novel to our environment (i.e., industrial chemicals, drugs, etc.). Unfortunately, cytochromes cannot protect us from every potential threat. Many natural and manmade toxins are not effectively neutralized by cytochromes, and some compounds – certain drugs and insecticides, for example – can actually become more poisonous when they are metabolized by cytochromes. Still other toxins exert their deleterious effects by altering the activity of one or more cytochromes: cyanide kills by interfering with cytochrome c’s electron-transferring capability, thereby halting oxidative phosphorylation and terminating all cellular energy production.
Although living organisms (including people) have a surprising capacity for detoxifying whatever we throw at them, that capacity cannot be infinite. The mechanisms cells rely on to protect themselves (and us) from toxic influences evolved in more pristine circumstances. While there is obviously some room for accommodation within these systems, we may be reaching the limits of their ability to adapt. We are unquestionably witnessing some of the effects of our inveterate irresponsibility: scientists point to manmade toxins as an underlying cause for extinctions of non-human species and for increasingly prevalent health problems among human populations. It isn’t clear how long we can continue on our current course until we overtax our already burdened planet. Despite the strident claims of those who advocate for a larger human presence in the only home we’ll ever know, it would be prudent to preserve and protect what we have.
1. Chemicals in the European Environment: Low Doses, High Stakes? The EEA and UNEP Annual Message 2 on the State of Europe’s Environment (October 1998)
2. Carlberg C. Genome-wide (over)view on the actions of vitamin D. Front Physiol. 2014;5:167
3. Deng J, Carbone I, Dean RA. The evolutionary history of cytochrome P450 genes in four filamentous Ascomycetes. BMC Evol Biol. 2007 Feb 26;7:30