Chapter 4 - The Chemistry of Life
As we have seen, life originated from replicators made up of some material similar to the current RNA
(ribonucleic acid), swarming around without protection against the environment. With time, natural selection would have
favored those replicators capable of capturing from the environment some sort of protected private milieu, capable of retaining an assortment of prebiotic materials necessary for their replication. The first cells would have then been created, containing the biological soup we call cytosol or cytoplasm, surrounded by a membrane. Within that soup would freely float the filament of genetic material, only later to be packed in the shape of a chromosome. From that moment on, genetic material replication would always be linked to cell duplication, every cell emerging only from another cell, through a standardized process: assimilation of ingredients through the covering membrane, replication of its genetic material, enlargement and bisection of the original
membrane.98 The creation of this special environment, separate from the outside world, seems to have been one of the most primitive and crucial features of life (Morange, 1998).
Although the cellular nature of life was recognized long before, the detailed study of cellular structure and development had to wait until the invention of the electronic microscope, introduced in scientific research after the 2nd World War. Thanks to it, we came to understand most cellular mechanisms, in particular, the singleness of life over the whole extension of our planet. Scientists came to realize that life employs the same basic structures, kind of molecules, chemical reactions, and uniform set of intercellular signals, wherever it occurs on the surface of the Earth. Furthermore, behind the diversity and complexity of the different vital processes, it was established that there exists a small number of basic biophysical actions with universal significance, some of the most important being the transfer of electrons and the transfer of chemical groups. All this has allowed us to conclude that, except for small details, there are no fundamental differences at molecular level between the cells of a human being, a worm, an orchid, or even an amoeba, a yeast or a bacterium, even if there is a vast variety of manners in which that essential plan is implemented in different types of cells or associations thereof.
As Christian de Duve has aptly put it, every living system should be capable of the following feats:
In order to build themselves and operate, living organisms obtain their constituents from simple natural oxides: hydrogen, from water (H2O); carbon, from carbon dioxide (CO2); nitrogen, from the nitrate ion (NO3) and sometimes from atmospheric nitrogen (N2); sulphur, from the sulfate ion (SO4); oxygen mostly from carbon dioxide (CO2), some times from water or other oxides. Autotrophic organisms, i.e., those which can directly live from exclusively mineral resources, manufacture out of them small organic molecules, immediately assembled into macromolecules: amino acids, to proteins; monosaccharides to oligosaccharides, polysaccharides and related substances; pentoses, puric and pyrimidic bases and phosphoric acid, to nucleotides; these in turn to nucleic acids; alcohols and diverse acids, to lipids and other esters; still many other assemblages. Heterotrophic organisms, on their part, mainly use premanufactured molecules, produced directly or indirectly by the above mentioned autotrophic industry. They are modified and combined in varied ways to make macromolecules similar to those build by autotrophs. Often and in both types of beings, macromolecules combine in their turn with each other to give birth to multi-macromolecular complexes, which in particular integrate granules, filaments, tubules, membranes, and other elements, integrating the structures found inside and around cells. These sort of giant aggregates, sometimes reinforced by mineral deposits, constitute the solid scaffoldings cooperatively erected by vegetal and animal cells in their innards and immediate surroundings, up to the molding of all visible structures found in the biosphere.
Notwithstanding the vast complexity of cellular structures, the principles that preside over their construction are surprisingly simple. They can be summarized almost entirely in two fundamental processes, both standing over the notion of transference: reduction-oxidation –electron transfer– and dehydrating condensation –chemical group transfer–.
Two molecules intervene in electron transfer, one richer in electrons than the other. The richer one, known as the reducing agent, cedes electrons to the poorer, known as the oxidized one.99 Autotrophic biosyntheses (such as those occurring in plants) require numerous reductions. Reduction, on the other hand, plays a much lesser role in heterotrophic organisms (such as animals), which mostly feed on already reduced substances. Notice that the electrons or hydrogen atoms required for this transfer do not exist free in nature; they have to be supplied by a particular molecule. The chemical reaction that performs the transfer is then both a reduction and an oxidation, a redox system. In principle, the transfer can take place in either of the two directions, but only the spontaneous one releases energy (it is technically called exergonic reaction); the opposing reaction (in the endergonic direction) cannot take place except in the presence of an energetic contribution.
The union of two biosynthetic materials occurs almost always through the loss of water according to the following formula:
X and Y represent any molecular groups. It is in this manner that proteins are born from amino
acids, the polysaccharides from sugars, and the nucleic acids from pentoses, bases, and phosphoric acid. Such reactions are the
reverse to the hydrolytic splits produced in the course of digestion, when the disintegration of large molecules into
their parts takes place. In the aqueous environment found in living systems, the exergonic direction, energetically
favored, is the one corresponding to a hydrolysis.100 Dehydrating condensation, on the other hand, is endergonic, it moves against the grain and cannot occur without a contribution of energy. Hence, the biosynthetic reaction must always be accompanied by another complementary reaction which supplies the needed energy: ATP101 hydrolysis, the energetic warehouse of the cell. Moreover, the two reactions must occur in tandem –as a kind of super-reaction– in order to preclude the possibility that the energy produced by the hydrolysis gets absorbed by the environment. The mechanism of this coupling is complicated and varies according to the materials used, but its principle is simple and universal. As a form of illustration, we present one of the possible hydrolyses of ATP:
ADP is adenosine diphosphate and P is a simple inorganic phosphate. To couple this reaction with the previous one we add their two formulas, eliminating the water in opposing sides, what produces
No water or energy is dispersed in the environment. One of the groups has been transferred, resulting in the biosynthesis of a large molecule formed by the X and Y groups. Since the procedure applies –as computer scientists would say– in a recursive way, after successive group transfers the molecule may become enormously large, like most proteins or nucleic acids.
The adenosine part of ATP is made of adenine –one of the four nitrogenous bases with which the genetic alphabet is built– and ribose, a five-carbon sugar. The three phosphate units, each one formed by one phosphoric atom and four oxygen atoms, are chained to the ribose. The links among the three phosphate groups are of high energy and easily yield. Here we show an example of the ATP hydrolysis according to the formula
This formula corresponds to the rupture of the link marked with a gamma in the figure. Such a hydrolysis produces, as we have seen, a certain quantity of energy, degrading the ATP to adenosine diphosphate (ADP) and a simple inorganic phosphate. If the rupture takes place rather at the beta link, we will have an alternative hydrolysis that degrades ATP to adenosine monophosphate (AMP) and a pyrophosphate (double sulfate). By any of these two hydrolyses, the ATP molecule will timely supply –through conversion to ADP or AMP– the necessary energy for all cellular jobs, such as transmission of nervous signals, muscular contraction, protein synthesis, or cellular division. The ADP or the AMP will recover the lost phosphate groups thanks to the respiration process explained immediately below.
Animal cells derive their energy from food, through a process called respiration. Plants, on their part, catch energy directly from solar light, through a different process called photosynthesis. Cytochromes, dark colored proteins that play a vital role in the transport of chemical energy in all cells, are intimately involved in both processes. They consist of a nitrogenous ring surrounding a metallic atom, such as iron or copper, to which they owe their distinctive color. They are embedded in the internal membranes of mitochondria –in vegetal and animal cells– or chloroplasts –in vegetal cells–.102 During respiration and photosynthesis, some of them accept electrons from proteins called coenzymes, in charge of cellular digestion, and then donate them –in cascade– to other cytochromes, through a series of chemical reactions known as the electron transport chain. This is a kind of electrical current, whose final destination is the large energy warehouse –a sort of battery– constituted by the powerful ATP.103
Let us concentrate on aerobic respiration, the one which produces more ATP.104 The first step occurs in the cytosol, the soup that surrounds the nucleus, and it involves the digestion (oxidation) of glucose. Each glucose molecule is composed of six carbon atoms, in addition to hydrogen and oxygen. When the glucose molecule breaks up, two molecules of pyruvic acid are formed, each one containing three carbon atoms. These reactions result in the formation of two ATP molecules. Some hydrogen atoms are also released in the process. In a second step, the pyruvic acid moves from the cytosol to the mitochondria, where subsequent reactions will occur. Each molecule of pyruvic acid combines with a protein known as coenzyme A, to form an acetyl coenzyme-A molecule –with two carbon atoms– and a carbon dioxide molecule –with only one. Hydrogen is also an important sub-product of this reaction. In a third step, the acetyl coenzyme A combines with four-carbon molecules to form citric acid, a six-carbon molecule. The citric acid then suffers a series of reactions that release energy, known as the citric acid cycle or Krebs cycle.105 In the course of this cycle, the citric acid progressively breaks in compounds of five or four carbons. The last compound of four carbons produced in the cycle combines with a new molecule of acetyl-A coenzyme forming citric acid, and the cycle begins again.
During the Krebs cycle, large quantities of energy are released and two ATP molecules are formed. Hydrogen is also released, forming carbon dioxide (with the lost carbon atoms). In the final step of aerobic respiration, the hydrogen atoms released during the first three steps will be received by the electron transport chain, which will proceed to separate the electron and proton of each one of those atoms. The electrons will be transmitted by the chain and will eventually combine with oxygen and protons to form water, with a great release of energy resulting in the formation of 34 ATP molecules, for a total number of 38 ATP molecules for the oxidation of each glucose molecule. The ATP will then be turned loose in the cell cytosol, becoming available for use in endergonic cell reactions. During each one of these energy applications and because of them, ATP will be degraded into ADP, substance which will eventually return to a mitochondrion, where it will take up an additional phosphoryl106 group, being upgraded once more to the triphosphate. This all-important process of regeneration is called, for obvious reasons, phosphorylation.
We need to become familiar with some basic concepts of genetics to orient ourselves in the contemporary scientific doctrines concerning life. Let us begin by recalling that modern genetics has its roots in the research involving pea crossings performed in 1865 by the Austrian monk Gregor Mendel (1822-1884) in the gardens of his monastery. That research led him to postulate that there were pairs of units in each plant representing hereditary traits. Those double units came from its parent plants, one from each parent and trait. Today, we call those units genes. We know they are located in the chromosomes, the complex structures furnished at each generation with genetic material coming at equal parts from each immediate progenitor.107
Chromosomes were described for the first time in 1872 by the German biologist Walther Flemming who followed their formation process during cellular division. In the year 1902, the American scientist W.S. Sutton pointed out the connection between chromosome activity during the division of sexual cells (meiosis) and the transmission of hereditary traits. The ease with which chromosome details can be observed in the salivary gland cells of the fruit fly (drosophila) allowed the study of their composition during the first part of the 20th century. On that basis, it was later determined that their active component was the giant molecule of deoxyribonucleic acid (DNA), the material conveyor of genetic information.
Within the DNA molecule, the part which contains genetic information is a sequence of substances called nucleotides. There are four types of them, the letters of a living alphabet which represent genetic information in digital form, each three-letter sequence specifying, apart from punctuation marks, one of the alpha amino acids.108 These are the molecular pieces that constitute proteins, blocks of which living beings are built as well as tools with which they perform their functions within the organism. Amino acids belong to a class of relatively simple organic109 molecules, called monomers. As such, they can react with similar molecules to form double ones (called dimers), or even chains of indefinite extension (polymers). The process of forming these organic chains is called polymerization.
The essential feature of a monomer is its polyfunctionality, i.e., its ability to chemically link with other organic compounds. There are bifunctional ones, able to form long linear chains, as well as other of higher functionality, capable of forming complex chemical webs. Polymers are macromolecules, multiples of monomers. They constitute the vast majority of the living-beings materials, including proteins, cellulose, and nucleic acids. Cellulose, which the stronger parts of plants are made of, is a polysaccharide, i.e., a polymer composed of sugar molecules. Proteins, on their part, are amino-acid polymers; nucleic acids (the components of chromosomal DNA) are polymers composed of nucleotides, complex molecules integrated by nitrogenous bases (the letters of the genetic code) plus sugar and phosphoric acid (the scaffolding which supports the text written in the code).
This is the way in which atoms join together within one of the four kinds of nucleotides:
molecule110 may be thought of as composed of two halves: a message part (bold font on the right side of the previous image) and a skeleton part (regular font on the left side). Each nucleotide has the same skeleton part, but its message part is either adenine (A) or guanine (G) or thymine (T) or cytosine (C). Below the remaining three letter structures:
One of the great findings of the 20th century in the field of biological sciences was the
determination of the DNA molecular structure. It was discovered that it is a double helix, i.e., two mutually
complementing strands, each one containing, as just mentioned, a chain of nucleotides integrated by a phosphoric acid, a
sugar (desoxyribose), and a nitrogenous base. The cellular machinery is able to interpret a sequence of three consecutive
bases as a letter of an alphabet. The phosphates and sugars in each strand coil around its counterpart, forming a double
helix, the nitrogenous bases coupling weakly the two strands. These bases are either puric ones (adenine and guanine) or
pyrimidic ones (cytosine and thymine). The corresponding bases of the two chains have a reciprocal affinity
which keeps them united, although they easily separate with the torsion applied by the polymerase enzyme. These weak
unions, technically known as hydrogen bonds, associate a puric base from one strand with a complementary pyrimidic
base from the other (A-T, G-C). Hence, from the composition of one of the DNA strands necessarily follows the composition
of its complement and only one of the strands needs to be read as blueprint for the construction of proteins.
A fascinating aspect in the DNA molecule, which kept researchers perplexed for years, is its non monotonic character. That is, the order of bases along the chain varies in a seemingly random way, apparently nonsensical but in fact resulting from the mechanics of sexual inheritance and hence determining the uniqueness of each individual of any particular species. The DNA examination of a complete human chromosome, for instance, corresponds to a sequence of many thousands of bases, unique for each individual phenotype. Both the uniqueness of each living being and the reciprocal belonging of all of them rests assured upon the grounds of the non monotonicity111 and the basic uniformity of the genetic material.
Proteins are created by polymerization of amino acids through special unions called peptide bonds. When a cell makes a protein, the carboxyl group of an amino acid sticks to the amino group of another amino acid in order to form a peptide bond. The carboxyl group of the second amino acid sticks in a similar way to the amino group of a third, and so on, until a long chain is formed. This chained molecule can contain from fifty to several hundreds of amino acid subunits, a polypeptide. A protein can be formed by only one polypeptide chain or by several of these joined together. Each protein is created according to a clear set of instructions contained in the genetic information of the cell. Such instructions determine which of the 20 amino acids must be incorporated into the protein, and in what order. The radical groups of amino acids (undefined and identified with an R in the figure) determine the final form of the protein and its chemical properties. An extraordinary variety of proteins can be produced starting from the same twenty subunits. Proteins have the property to fold over themselves in a peculiar way, thus acquiring the three-dimensional shape that qualifies them to interact reactively with other large molecules, especially DNA, RNA, and other proteins, in order to fulfill their role as both artificers and materials of life.
We call enzymes the proteins which act as tools in the construction and maintenance of an organism. They combine themselves reactively with the substance to be affected, separating from them once the job is done. The polymerase enzyme is the most famous of them all, since it is in charge of reproducing DNA. It basically separates the two strands of the dual helix, facilitating their completion with nucleotides floating in the cellular soup. The term polymerase comes from the word “polymer,” the ending “ase,” being the conventional identification of proteins which act as enzymes. Thus, polymerase is the enzyme that polymerizes (creates polymers), particularly DNA and RNA. This enzymatic or –as it is also called– catalytic function is one of the tasks performed by proteins, their function as organic tools. The other function they play is that of biological building blocks, indispensable main constituents of most cellular structures.
The DNA, locked-up in the nucleus of each eukaryotic cell (such as the ones of human beings or plants and animals) to better protect the important information which defines the species, can neither build the organism directly nor keep watch over its operation. It requires to the effect some reliable messengers which, leaving the nucleus and roaming in the surrounding cytosol, are able to interact with the “protein factories” (the ribosomes)112 and their construction materials (the amino acids, freely floating in the biological soup), following strict instructions from their master.113 Those errand porters or messengers are molecules that resemble DNA, with a very similar composition: ribonucleic acid (RNA). The main difference between the two substances is that RNA contains the nitrogenous base uracil (U) wherever DNA carries thymine (T). RNA chains have the ability to mate with each other as dual helices, although they seldom do. They do it regularly with monocatenary DNA, since uracil associates with adenine equally well as thymine does. More often, though, RNA acts, in its regular function as protein originator, as an independent or monocatenary strand (a simple chain), not mated in double-helix chains. Moreover, it is usually a much shorter molecule, since its main function is to serve as messenger of DNA, expressing the genes in a particular bodily region at particular times and circumstances.
The fact that the link between the two DNA strands is weak enables their temporal separation (necessary for genes expression) or their definitive one (necessary for DNA duplication). In the former case, one of the strands temporarily separated, called “active” or “positive,” forms a bubble serving as pattern to generate the RNA messenger assigned to direct the construction of a protein. We say that a gene is expressing itself (through the RNA and, ultimately, the corresponding protein). In the latter one, each of the two strands generates its own complement, duplicating the DNA molecule as part of the regular cell-division process. We say that the cell is replicating itself. Both processes occur with the collaboration of the powerful polymerase enzyme, in charge of the job of catching the necessary materials (sugars, phosphoric acid, nitrogenous bases) from the cytosol. The progressive assemblage in both cases is done following the pattern of the model strand and taking advantage of the complementariness of the nitrogenous bases.114
Note 98: From its very first origin, and as a cell from another cell, a membrane will always emerge from another membrane.
Note 99: In numerous occasions, protons and electrons are mobilized at the same time. Remember: 1 proton + 1 electron = 1 hydrogen atom.
Note 100: An hydrolysis is a chemical reaction in which one water molecule (HOH) reacts with a molecule of a substance (AB) formed by atoms or groups of atoms (A and B). In the reaction, the water molecule breaks into the fragments H+ and OH-; the molecule of the other substance breaks into A+ and B-; these fragments unite to give the final products AOH and HB.
Note 101: Adenosine triphosphate.
Note 102: We know that mitochondria, like chloroplasts, are ancient bacteria that entered into an endosymbiotic relationship with their current host cells. In the case of bacteria themselves, the cytochromes are embedded in their own surrounding membrane.
Note 103: See Appendix L: MITOCHONDRIA.
Note 104: The other respiration process, called anaerobic respiration, occurs in certain cells of the body submitted to a lack of oxygen, especially muscular cells during strong exercising. The Krebs cycle –explained immediately– does not occur in anaerobic respiration; the final product of energy is much lesser: two ATP molecules per each glucose molecule.
Note 105: So named in honor of Sir Hans Adolf Krebs, a British biochemist who described its essential steps in 1937.
Note 106: The radical PO.
Note 107: See Appendix A: MENDELIAN INHERITANCE.
Note 108: See Appendix G: AMINO ACIDS.
Note 109: 'Organic' in this case means simply “based on carbon chemistry.”
Note 110: The complete molecule is the DNA strand.
Note 111: The non monotonicity of the genetic material rest on the fact that each pair of alleles of two homologous chromosomes is susceptible of having varied values for the same gene, as first adumbrated by the methodical monk Gregor Mendel early in the 19th century.
Note 112: See Appendix J: RIBOSOMES.
Note 113: We allow us the freedom to use figurative language in order to facilitate learning. We trust that the reader already understands clearly that in nature there are no ends, neither anyone giving or obeying orders, but rather material factors who act blindly following the laws of nature. If this liberal use of language is confusing, we recommend the reader to consult Daniel Dennett’s work on intensional (yes, with an "s") systems (Dennett, 1981).
Note 114: The existence of those ingredients in the environment is necessary for the job, as well as that of an oligonucleotide ("oligo" for short), small peptide formed by a few nucleotides which must act as a primer for the reaction to get started.