Dr. Betty Kamen, Ph.D.

Table Talk Health Hints

The History Of Oxygen On Planet Earth

If Oxygen is so damaging to cells, how did life ever get started on earth? Wouldn't any living cell be wiped out immediately?

The simple answer is that the "prebiotic" atmosphere of earth which gave rise to the earliest forms of life had little or no free oxygen. Four billion years ago, Methane, ammonia, hydrogen, and carbon dioxide were the most likely constituents of our planet's atmosphere. There was no ozone layer to block ultraviolet solar radiation, and there was a high level of electrical energy discharge through lightning. This was the "primordial soup" that produced the first self-replicating chains of molecules, and the first living organisms.

In laboratory experiments that attempt to duplicate these conditions, four important classes of organic chemicals are created by purely chemical reactions: Amino acids, nucleotides, sugars, and fatty acids. Amino acids and nucleotides can also join to each other to form long chains. When amino acids do this they resemble proteins. There are only 20 different amino acids used to assemble proteins. When nucleotides link up into long chains they can form ribonucleic acids (RNA) and deoxyribonucleic acids (DNA). What's more, a chain of nucleotides can be self-replicating: One chain of certain types of nucleotides will cause other chains to be formed with the same sequence of nucleotides, after a few chemical steps. Only four of the many possible nucleotides are used. All very chemical, even mechanical, but amazingly life- like. And even more amazing, RNA can manufacture proteins from amino acids, simply by folding over and binding to itlself to form certain complicated shapes defined by the sequence of those four constituent nucleotides.

In modern cells the process is considerably more complex. Because RNA is fairly easily damaged and altered, the genetic information is stored in DNA, while RNA translates the code into enzymes that do the work of making proteins.

The role of the fatty acids is vital also. Some fatty acids have the property of forming a molecular bilayer, or a film just two molecules thick, when placed in a water environment. This is because one end of these fatty acids is similar to substances that dissolve in water (water-soluble), while the other end is oil-like, and will not dissolve in water (fat-soluble). It's true that "oil and water don't mix." Looking for, and finding, the "easiest" solution to this dilemma, nature assembles the molecules in a double layer with the fat- soluble oil-like ends of the molecules on the inside of the layer, and the water soluble ends outward. So both exposed surfaces of the film get along fine with the surrounding water. This film ends up being about 5 nanometers thick - that's about one five-millionth of an inch. But what to do about the edges? Easy answer - wrap the film into a bubble, so there are no edges. And so is born the cell membrane. A water solution outside, a water solution inside, and fat-like substances within the molecular bilayer.

Once primitive RNA found its way inside the fatty acid membrane, then RNA could evolve to more complicated forms, protected from competing reactants. It could also protect itself from the changing external environment, because now there is an "inside" and an "outside." Remember that all this early development of living cells takes place in an environment of essentially no oxygen. The energy to run the processes that create these chemical building blocks comes directly from the environment - from heat, light, and radiation on the primitive earth. Some of the available hydrocarbons, including some sugars, are more stable in somewhat different forms than how they are found in the prebiotic soup, and so there is energy available on the chemical level as these materials are broken down. Glycolysis, for example, is the process of breaking down glucose into lactic acid or ethanol, and energy. It's a fundamental function of every living cell, and is part of one process by which adenosine triphosphate (ATP) is produced. More about ATP later. It's one of the most common and versatile sources of chemical energy at the cellular level.

All this happens without oxygen. Free oxygen in this picture would not only be unnecessary - it would be incredibly destructive. Compared to the complacent rates of chemical reaction in the prebiotic environment, a reaction with free oxygen would be like putting a blow torch to the blueprints. Life could never have gotten started on earth if there was oxygen in the atmosphere! At least - at the risk of sinking into an over-worn cliché - not "life as we know it."

Where did all this oxygen come from, then, and why doesn't it destroy all forms of life in an instant?

Living cells are thought to have appeared some 3.5 billion years ago, but it was only 1.5 billion years ago that cells began to use oxygen for energy. Photosynthesis, however, is thought to have begun a mere hundred million years or so after the first living cells. This is the process of obtaining energy directly from sunlight, and it was motivated by the need to get carbon and nitrogen from increasingly stable compounds, as the supply of more reactive substances diminished. But carbon from carbon dioxide (CO2) and reactive nigtrogen from the two-atom nitrogen molecule (N2) are hard to get. Both forms are already fully "oxidized" and very stable - takes a lot of energy to get the carbon or nitrogen out. Radiant energy from sunlight provides this concentrated energy source. In a multi-step process involving chlorophyll, hydrogen split from water molecules (H2O), and the reactive hydrogen is able to break the carbon and nitrogen free of the stable molecules. provides the necessary energy to free the carbon or nitrogen. The major by-product is oxygen, released in molecular form as O2. The first anti-oxidants probably evolved at exactly the same time, to prevent the reactive oxygen from undoing the work of the photosynthesis process.

Actually, the earliest form of photosynthesis probably used H2S to obtain those energetic hydrogen atoms, and the waste product was Sulfur. Sulfur is also an "oxidizing agent" in the more general sense, because it bonds to other atoms by "stealing" two extra electrons. Zinc seems to be one of the most effective antioxidants when sulfur is involved, and its use as an antioxidant may go all the way back to these first photosynthesizing cells. But as the available H2S diminished over many millions of years, photosynthesis involving water became the dominant process, and the major waste product was free oxygen.

What happened to this free oxygen?

Everything went along fine for about a billion years. There was a a significant amount of free iron in the earth's oceans, and the O2 released from photosynthesis combined with the iron to form iron oxide and fell to the ocean floor. But then, "suddenly," the supply of iron ran out. The oxygen levels in the oceans and the atmosphere began to rise. (see figure 1, "Oxygen History") This was actually bad news for most existing life forms, because oxygen is of course highly toxic to the anaerobic life forms of the time, neutralizing enzymes and damaging DNA and RNA. Cells began to evolve with protective structures to keep oxygen out.

When this happened, symbiotic relations developed between cells that were good at performing photosynthesis and cells that provided the necessary protection from a hostile environment. A whole new and more complex kind of cell evolved, where one cell eventually engulfed the other. Chloroplasts, the organelles or sub-structures within modern cells that engage in photosynthesis, are the result of this relationship. Chloroplasts still retain some of their own DNA, and it bears a traceable relationship to simpler forms of photosynthesizing single-cell organisms.

The story doesn't end here, though. As oxygen levels continue to rise, a powerful new source of energy was available to be exploited. Instead of the relatively inefficient glycolisis process, glucose could now be broken down all the way down to CO2 and H2O, if only the oxygen could be handled safely. Certain bacteria evolved that specialized in this process, but as the oxygen concentration in the environment continued to increase, they too sought protection within the "castle walls" of other cells.

In animal cells, all the reactions involving oxygen take place in organelles called mitochondria. Like chloroplasts, mitochondria have their own enclosing membrane, their own DNA, manufacture some of their own proteins, and can reproduce by dividing in two. Without mitochondria, the cells would be virtually anaerobic, as none of the chemical reactions involve oxygen. In fact, free oxygen remains extremely toxic to just about every part of the modern animal cell except the mitochondria, and to the mechanism for getting oxygen in and out.

So we see what an unlikely combination of chemical accidents we are made of. Respiration, the cellular process by which most ATP is now produced, and the mechanism for powering just about everything our bodies do, is delegated to a the evolved remnants of a symbiotic oxygen-using bacteria. It came about only because other sunlight-utilizing bacteria and algae made enough oxygen to use up the ocean's supply of free iron, and that happened only because earlier life forms found ways to get free carbon and nitrogen out of the materials at hand. What a long strange trip it's been!

Thankfully, oxygen levels tapered off and stabilized about a billion years ago, and now comprise 21% of the air we breathe.

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