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Water: The Molecule of Life
Mar 1, 2008

The sustenance of all known life-forms relies heavily on water, and almost all living things are mostly composed of water. The chemistry of biological reactions is based on water, which renders conditions suitable for living things also on the global scale. Because water is indispensable for maintaining life, scientists first look for traces of it when searching for extraterrestrial life. As the habitat for many life-forms, seventy-five percent of the earth’s surface is covered with water, which is one of the most abundant substances on earth. Ironic as it may seem, water-one of the simplest and undoubtedly the most ubiquitous liquids -proves itself perhaps the most unusual molecule on our blue planet.

Most, if not all, of water’s anomalous properties make life possible. To name a few of its many oddities, water is the only material that naturally exists in all possible forms (solid, liquid, and gas) on earth. Of all known chemical compounds, water has the second highest capacity to store heat, which is crucial for climate regulation and keeping living organisms’ body temperatures constant. Water is the second best heat-conducting liquid (after mercury), and this helps large masses of water to reach uniform temperatures quickly. Water has an astonishingly high heat of vaporization which eases body temperature regulation for humans and animals via providing a cooling system through sweating. This high heat of vaporization also prevents dehydration.

The absorption coefficient of water is a million times lower for the visible region of light than the rest of spectrum, a property which enables passage of the useful and prevention of the harmful rays from the sun, and makes the earth amenable to the accommodation of biological life. Furthermore, the greenhouse effect which keeps the Earth’s climate at moderation also stems from this aspect of water. Because the sunlight that is reflected from the Earth is mostly in the infrared region, it is effectively absorbed by the water vapor in the atmosphere due to water’s higher absorption of light within the non-visible regimes, and hence the heat does not escape from the earth.

Water is one if the best solvents, which is very important for cleansing. Finally (and thankfully), water does not display its peculiarity when it comes to taste. Such a “famously odd” molecule is somewhat ironically tasteless and odorless, and extremely easy to drink and consume.

“If We so willed, We would make it bitter and salty. Then should you not give thanks?” Waqi‘ah (56:70)

Although each of the aforementioned physical aspects of water deserves mentioning in its own right, from here on we will focus on water’s properties from a biological standpoint. To this end, we will first introduce some aspects of water, look at the interaction of water with bio-molecules, and finally elaborate on three particular biological examples (protein folding, cellular membranes and water channels), which demonstrate how such interactions provide the bases for life.

Life based on water

“We made every living thing from water.” Anbiya 21:30

Thanks to its abundance on earth, water is easily accessible and inexpensive. However, in the summer of 1986, Professor Michael Levitt of Stanford University spent almost half a million dollars on a tiny amount of water, that would hardly wet the point of a pin. Certainly, the money was not spent on the water itself, but the expenditure (it now costs about 50 cents to run such a simulation) reflected the cost of running a simulation on a cluster of supercomputers for two weeks to understand the interaction between water molecules and a particular protein. Eventually, the money turned out to be well spent. Although the same protein had been modeled before by a research group at Harvard University in 1977, the simulation had been carried out as if the protein were in a vacuum. Levitt and his co-workers realized that the previous attempt to model the proteins in the absence of water was a poor predictor of the real-life scenario. Likewise, earlier DNA simulations meant to model the double helical DNA in the absence of water had failed, Levitt and his colleagues also succeeded in simulating the DNA by adding water in the environment, and the water molecules were found to be interacting with nearly every part of the DNA. Levitt’s groundbreaking discoveries not only revealed the importance of the interaction between water and biological molecules, but also paved the way for computational biologists to simulate biological entities in the presence of their native watery media.

When a drop of oil is placed in water, it does not mix with water. Hence, oil and water are said to be immiscible. In contrast, sugar easily dissolves in water and forms a homogenous mixture upon mixing. Although not as obvious at first sight, the underlying principles which govern this phenomenon can explain how water can interact with biological molecules.

Materials can be classified according to their “water tendency”: the ones that tend to avoid water (e.g. oil), are considered hydro-phobic (hydro: “water,” phobic: “fearing”), whereas materials that mix well with water (e.g. alcohol) are called hydro-philic (or water-loving). Water’s particular molecular structure turns out to yield a non-uniform electron distribution, and thus makes water molecule highly “polar” (see Figure 1.a). As a consequence, polar or charged molecules prefer being close to water molecules, whereas the apolar or neutral ones tend to avoid them.

Many curious aspects of water stem from another fact-that water molecules can interact with each other through “hydrogen bonding” (see Figure 1b). Although the molecules in a liquid are highly disordered, hydrogen bonding gives water molecules some order even in the liquid phase. A molecule’s ability to cooperate in hydrogen bonding is very important for breaking (or formation) of hydrogen bonds, and affect two parameters (i.e. the “order” and the “energy”) of the system which determine the feasibility of a certain chemical reaction.

Actually, most, if not all, of the oddities of water are due to these two properties (water-tendency and hydrogen bonding). Furthermore, these two aspects determine a great deal of how water interacts with other molecules, and the way water enables the proliferation of life. We will now elaborate on some biological phenomena and try to understand them in the light of these aspects of water.

Protein folding

Proteins are biological molecules that carry out the vital tasks of life. In the cell, proteins are initially synthesized as linear chains of amino acids ranging in size from a few to several thousand amino acids in length. Subsequent to synthesis, a linear chain spontaneously folds into a particular three-dimensional (3D) form (see Figure 2). This precise fold is essential for the execution of protein’s specific function (see Figure 3). As simple as it may sound, protein folding is currently one of the biggest questions in biophysics.

Researchers are working hard to be able to devise principles to estimate which 3D fold a certain linear amino acid sequence adopts, and what functions the eventual 3D structures execute. Although these questions related to the protein folding phenomenon are still far from being totally understood, some clues have been discovered.

In 1969 Cryus Levinthal stated that an average size protein would fold within about 1030 times longer than the expected lifetime of the universe if it were to fold via sampling all possible conformations even if the conformational sampling is very fast (e.g. a millionth of a millionth of a second for each conformation). This obviously is not what happens in reality, and the experimentally observed folding times are within milliseconds (a thousandth of a second) – second regime. This discrepancy between the estimated and the measured timescales is referred to as the “Levinthal Paradox.”

Consequently, proteins cannot rely on randomly sampling all the possible conformations to fold, but the folding must rather be a driven and directed process. Scientists hypothesize that water comes to the rescue at this point. As the linear protein chain is being synthesized, water-hating amino acids try to bury themselves away from water as soon as possible. This leads to the rapid collapse of the linear amino acid chain into a compact structure where hydrophobic regions are protected from water (see Figure 2c). This initial compaction which is provided by the interaction with the ambient aqueous medium is thought to be the key step in achieving folding within reasonable timescales. After the first rapid compaction, the protein adapts its final structure by sampling a much smaller number of possible conformations.

Simultaneously, hydrogen bonding helps the stabilization of certain folds with respect to other possible structures and contributes to the folding process. Eventually, the functional 3D fold is thus realized from the nascent linear protein chain.

Cellular compartmentalization

“He has let flow forth the two large bodies of water, they meet together, (but) between them is a barrier, which they do not transgress (and so they do not merge).” (Rahman 55:19-20)

Compartmentalization is an important feature of life. First of all, the boundary of a cell must be well-defined and well-controlled. Secondly, different tasks are carried out by specialized compartments (so called organelles) within most of the cells. The major design principle of the cellular boundaries depends on the immiscibility of water and oil. The subunits of cellular membranes are “lipids” which simply are oil-based molecules. A lipid molecule has two parts: A water-loving “headgroup” and two water-fearing “tails”. Because of the dual water-tendency of lipids, they can self assemble into bi-layers (see Figure 4 a and b), which eventually form enclosed structures. Thanks to the properties of water, this compartmentalization is readily achieved.

The cell membrane thus formed is impermeable to ions, and many chemical agents important for sustaining the cellular functions. Although such a barrier is essential for holding the cell contents as well as maintaining intracellular balance, material exchange between inside and outside of the cell is also an indispensible trait for carrying out the vast majority of vital processes (nerve impulse formation and transmission, cell signaling, nutrition, etc.). In order to achieve well-controlled material transport across the membrane, the cell membrane is decorated with various proteins that function as “channels” (see Figure 4c). These channel proteins come in different flavors and show specificity towards different chemicals. For instance, the channel protein for the potassium ion (K+) only allows the passage of potassium ions, whereas the sodium channel only lets sodium (Na+) through. Other channels have “gating” mechanisms that enable the channel to be “open” or “closed” depending on the need for the transport to happen. Although the specificity and gating mechanism of every channel protein relies on a unique ingenious design principle which deserves detailed mention in its own right, in the rest of the article we will focus on the water channel, for it once again exemplifies the perfect harmony between water and the bio-molecules.

Aquaporin: The water channel

Almost 170 liters of water is recycled in the human kidney on a daily basis, and this requires that kidney tissue possesses high water permeability. Since water cannot diffuse in and out of the cell membrane very rapidly for the reasons given above, reconciliation of the enormous daily flux of water in the kidneys has been a long-standing puzzle. The discovery of water channels (also known as “aquaporin”) by Peter Agre in 1992 resolved the mystery, and this finding was awarded the Nobel Prize in Chemistry in 2003. It is now known that the recycling machinery in the kidney chiefly consists of millions of aquaporins. Like other channel proteins, aquaporins also display selectivity: water is effectively transported across aquaporins, whereas the passage of other ions and miscellaneous agents is not permitted.

However, how this selectivity is achieved presented another riddle: Hydrogen is smaller than water and can move through the smallest opening. How, then, is the hydrogen selected against, while water is allowed? It was also well known that water molecules which are ordered within the channel constriction (see Figure 5) normally form a “proton wire” through which the hydrogen ions (i.e. protons) can easily flow just like an electrical current flows along an electrical wire. Thus, as water is transported across aquaporins, hydrogen ions should in principle move rapidly in and out of the cells through the chain of ordered water molecules (i.e. the proton wire) in an uncontrollable manner. This would cause an imbalance in the cellular environment, and most likely would lead to cell death.

The answer came from a computer simulation of aquaporin by Emad Tajkhorshid and Klaus Schulten at the University of Illinois at Urbana Champaign. They found that the water molecules change their orientation (see Figure 5) as they spun through the water channel. This rotation was achieved via water molecules’ specific interactions with the amino acid residues in the channel. Thanks to this orientation, the formation of the proton wire is disrupted (just like a break in an electric circuit) and the hydrogen ions are not permitted through the channel, while rapid water diffusion takes place. The interaction between water and aquaporin thus provides just another reason water is rightfully considered the cradle of life.

Conclusion

"There are only two ways to live your life. One is as though nothing is a miracle. The other is as though everything is a miracle." Albert Einstein

… and that He sends down water from the sky, and revives with it the earth after its death. Surely in this are signs for people who will reason and understand. Rum 30:24 

References

1. Gedik, N. “The Miracles of Water,” The Fountain, Issue 43, January–March 2005.

2. Ileri, R. “Water and Vitality,” The Fountain, Issue 2, April-June 1993.

3. Unal, Ali. The Qur’an: An Annotated Interpretation in Modern English, The Light, Inc. NJ: 2005.

4. “Simulating Water and The Molecules of Life,” Scientific American, November 1998.

5. Errington, J. R. & Debenedetti, “P.G.” Nature, 409, 318–321, 2001.

6. Water, Wikipedia.

7. “Mysteries of Water,” Physics Today, June 2003.

8. Sener, Hamdi. “Mikroalemdeki Canli Motorlar” (Living Engines in the Micro World), Sizinti, September 2005.

9. Figures are modified from: Chemical polarity, Wikipedia
Hydrogen bond, Wikipedia
http://www.ccl.net/cca/documents/dyoung/water/
http://www.helsinki.fi/~jtvaara/images/water.gif
“Inner Life of The Cell” animation, http://multimedia.mcb.harvard.edu/
“Molecular Biology of the Cell,” 4th Edition; Bruce Alberts et al.
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http://www.mja.com.au/public/issues/179_11_011203/van10722_fm-5.jpg