Life as Phenomenon of Universe

1.3.1. Biotic Role of Large Molecules

Theories of the Origin of Life

Living things are composed of the same elements as the inanimate universe - the 92 elements of the periodic table. But the arrangements of these atoms into molecules in biological systems are unique. You cannot find DNA in rocks unless it came from a once-living organism. How life began on Earth sometime during the 600 million ears of the Hadean is impossible for us to know for certain, given the vast amount of time that has passed. There are two theories of the origin of life: life from extraterrestrial sources, and chemical evolution.

Comets probably brought Earth most of its water. The meteorites described at the beginning of this chapter are evidence that molecules characteristic of life may have travelled to Earth from space. Taken together, these two observations suggest that some of life’s complex molecules could have come from space. Although the presence of such molecules in rocks may suggest that those rocks once harboured life, it does not prove that there were living things in the rocks when they landed on Earth. Claims that the spherical objects seen in ALH 84001 are the remnants of ancient Martian organisms are far from accepted by all scientists in the field. Most scientists find it hard to believe that an organism in a meteorite could survive thousands of years travelling through space followed by intense heat as it passed through Earth’s atmosphere. But there is some evidence that the heat inside some meteorites may not have been severe. When weakly magnetized rock is heated, it reorients its magnetic field to align with the magnetic field around it. In the case of ALH 84001, this would have been Earth’s powerful magnetic field which would have affected the meteorite as it approached our planet. Careful measurements indicate that, while reorientation did occur at the surface of the rock, it did not occur in the inside. The scientists who took these measurements, Benjamin Weiss and Joseph Kirschvink at the California Institute of Technology, claim that the inside of ALH 84001 was never heated over 40oC on its trip to Antarctica, making a long interplanetary trip by living organisms more plausible.

Both Earth and Mars once had the water and other simple molecules that could, under the right conditions, form the large molecules unique to life. The second theory of the origin of life on Earth, chemical evolution, holds that conditions on the primitive Earth led to the emergence of these molecules. Scientists have sought to reconstruct those primitive conditions. Early in the twentieth century, researchers proposed that there was little oxygen gas (O₂) in Earth’s first atmosphere (unlike today when it constitutes 21 percent of our atmosphere). O₂ is thought to have accumulated in quantity about 2.5 billion years ago as the by-product of the metabolism of single-celled life forms. In the 1950s, Stanley Miller and Harold Urey set up an experimental “primitive” atmosphere, containing hydrogen gas, ammonia, methane gas and water vapour. Through these gases, they passed a spark to simulate lightning, and then cooled the system so the gases would condense and collect in a watery solution or “ocean”. Within days, the system contained numerous complex molecules, including amino acids, purines and pyrimidines— some of the building blocks of life. In science, an experiment and its results must be constantly reinterpreted and refined as more knowledge accumulates. The results of the Miller-Urey experiments have undergone several such refinements. In living organisms, many molecules have a unique three-dimensional “handedness”. The amino acids, for example, are all in the L-configuration. But the amino acids formed in the Miller-Urey experiments were a mixture of the D- and L-forms. Recent experiments show that natural processes could have selected the L-amino acids from the mixture. Some minerals, especially calcite-based rocks, have unique crystal structures that selectively bind to D- or L-amino acids, separating the two. Such rocks were abundant during the Archean. Scientists’ views of Earth’s original atmosphere have changed since Miller and Urey did their experiment. There is abundant evidence of major volcanic eruptions 4 billion years ago that released carbon dioxide (CO₂), nitrogen (N₂), hydrogen sulphide (H₂S) and sulphur dioxide (SO₂). Prebiotic chemistry experiments using these molecules in addition to the ones in the original “soup” have led to more diverse molecules.

Long polymers had to be formed from simpler building blocks called monomers. Scientists have used model systems to try to simulate conditions under which polymers could be made. Solid mineral surfaces, such as finely divided clays, seem to provide the best environment to bind monomers and allow them to polymerize.

A. Oparin, as well as much later Miller and Urey, suggested that life originated in hot pools at the edges of oceans. Because life has been found in many extreme environments on earth, scientists have proposed that such environments— found beneath ice, in deep-sea hydrothermal vents and within fine clays near the shore—could be the original site of life’s emergence. In whatever way the earliest stages of chemical evolution occurred, they resulted in the emergence of monomers and polymers that have probably remained unchanged in their general structure and function for 3.8 billion years. We now turn our attention to these large molecules.

Macromolecules: Giant Polymers

The four kinds of large molecules are made the same way and they are present in roughly the same proportions in all living organisms. A protein that has a certain role in an apple tree probably has a similar role in a human being because their basic chemistry is the same. One important advantage of this biochemical unity is that organisms acquire needed biochemicals by eating other organisms. When you eat an apple, the molecules you take in include carbohydrates, lipids and proteins that can be refashioned into the special varieties of those molecules used by humans.

Macromolecules are giant polymers (poly-, “many”; -mer, “unit”) constructed by the covalent linking of smaller molecules called monomers. These monomers may or may not be identical, but they always have similar chemical structures. Molecules with molecular weights exceeding 1,000 are usually considered macromolecules, and the proteins, polysaccharides (large carbohydrates) and nucleic acids of living systems certainly fall into this category. Each type of macromolecule performs some combination of functions: energy storage, structural support, protection, catalysis, transport, defence, regulation, movement and information storage. These roles are not necessarily exclusive. For example, both carbohydrates and proteins can play structural roles, supporting and protecting tissues and organisms. However, only nucleic acids specialize in information storage and function as hereditary material carrying both species and individual traits from generation to generation. The functions of macromolecules are directly related to their shapes and to the sequences and chemical properties of their monomers. Some macromolecules fold into compact spherical forms with surface features that make them water-soluble and capable of intimate interaction with other molecules. Other proteins and carbohydrates form long, fibrous systems that provide strength and rigidity to cells and organisms. Still other long, thin assemblies of proteins can contract and cause movement. Because macromolecules are so large, they contain many different functional groups. For example, a large protein may contain hydrophobic, polar and charged functional groups that give specific properties to local sites on the macromolecule. As we will see, this diversity of properties determines the shapes of macromolecules and their interactions with both other macromolecules and smaller molecules.

Condensation and Hydrolysis Reactions

Polymers are constructed from monomers by a series of reactions called condensation reactions or dehydration reactions (both terms refer to the loss of water). Condensation reactions result in covalently bonded monomers and release a molecule of water for each bond formed. The condensation reactions that produce the different kinds of polymers differ in detail, but in all cases, polymers form only if energy is added to the system. In living systems, specific energy-rich molecules supply this energy. The reverse of a condensation reaction is a hydrolysis reaction (hydro-, “water”; -lysis, “break”). Hydrolysis reactions digest polymers and produce monomers. Water reacts with the bonds that link the polymer together and the products are free monomers. The elements (H and O) of H₂O become part of the products. These two types of reactions are universal in living things and as we have seen, were an important step in the origin of life in an aqueous environment. We begin our study of biological macromolecules with a very diverse group of polymers, the proteins.

Proteins: Polymers of Amino Acids

The functions of proteins include structural support, protection, transport, catalysis, defence, regulation and movement.

Among the functions of macromolecules listed earlier, only energy storage and information storage are not usually performed by proteins. Proteins range in size from small ones such as the RNA digesting enzyme ribonuclease A, which has a molecular weight of 5,733 and 51 amino acid residues, to huge molecules such as the cholesterol transport protein a polipoprotein B which has a molecular weight of 513,000 and 4,636 amino acid residues. (The word residue refers to a monomer when it is part of a polymer.) Each of these proteins consists of a single unbranched polymer of amino acids (a polypeptide chain), which is folded into a specific three-dimensional shape. Many proteins require more than one polypeptide chain to make up the functional unit. For example, the oxygen-carrying protein haemoglobin has four chains that are folded separately and associate together to make the functional protein. As we will see later in this book, numerous functional proteins can associate, forming “multi-protein machines” to carry out complex roles such as DNA synthesis.

The composition of a protein refers to the relative amounts of the different amino acids it contains. Not every protein contains all kinds of amino acids, nor an equal number of different ones. The diversity in amino acid content and sequence is the source of the diversity in protein structures and functions. The next several chapters will describe the many functions of proteins. To understand them, it is necessary first to explore a protein structure. The properties of amino acids will be examined and how they link together to form proteins. Then will sbe ystematically examined a protein structure and how a linear chain of amino acids is consistently folded into a compact three-dimensional shape. Finally, will be seen how this three-dimensional structure provides a specific physical and chemical environment that influences the interaction of other molecules with the protein.

Proteins are composed of amino acids

The structure of amino acids: identified four different groups attached to a central carbon atom – a hydrogen atom, an amino group (NH₃ +), a carboxyl group (COO–), - and a unique side chain or R group. The R groups of amino acids are important in determining the three-dimensional structure and function of the protein macromolecule. Amino acids are grouped and distinguished by their side chains.

The five amino acids that have electrically charged side chains attract water (are hydrophilic) and oppositely charged ions of all sorts.

The five amino acids that have polar side chains tend to form weak hydrogen bonds with water and with other polar or charged substances. These amino acids are hydrophilic.

Seven amino acids have side chains that are nonpolar hydrocarbons or very slightly modified hydrocarbons. In the watery environment of the cell, these hydrophobic side chains may cluster together in the interior of the protein. These amino acids are hydrophobic.

Three amino acids — cysteine, glycine and praline — are special cases, although their R groups are generally hydrophobic.

The cysteine side chain which has a terminal —SH group, can react with another cysteine side chain to form a covalent bond called a disulfide bridge (—S—S—). Disulfide bridges help determine how a polypeptide chain folds. When cysteine is not part of a disulfide bridge, its side chain is hydrophobic. The glycine side chain consists of a single hydrogen atom and is small enough to fit into tight corners in the interior of a protein molecule where a larger side chain could not fit. Proline differs from other amino acids because it possesses a modified amino group lacking a hydrogen on its nitrogen which limits its hydrogen-bonding ability. Also, the ring system system of proline limits rotation about its carbon, thus, proline isoften found at bends or loops in a protein.

Peptide linkages covalently bond amino acids together

When amino acids polymerize, the carboxyl and amino groups attached to the carbon are the reactive groups. The carboxyl group of one amino acid reacts with the amino group of another, undergoing a condensation reaction that forms a peptide linkage. (In living systems, other molecules must activate the amino acids in order for this reaction to proceed and there are intermediate steps in the process. Just as a sentence begins with a capital letter and ends with a period, polypeptide chains have a linear order. The chemical “capital letter” marking the beginning of a polypeptide is the amino group of the first amino acid in the chain and is known as the N terminus. The “punctuation mark” for the end of the chain is the carboxyl group of the last amino acid—the C terminus. All the other amino and carboxyl groups in the chain (except those in side chains) are involved in peptide bond formation, so they do not exist in the chain as “free,” intact groups (the “N →C” or “amino-to-carboxyl” orientation of polypeptides).

The peptide linkage has two characteristics that are important in the three-dimensional structure of proteins: unlike many single covalent bonds, in which the groups on either side of the bond are free to rotate in space, the C—N peptide linkage is relatively inflexible. The adjacent atoms (the alpha-carbons of the two adjacent amino acids) are not free to rotate because of the partial double bond character of the peptide bond. This characteristic limits the folding of the polypeptide chain. The oxygen bound to the carbon (C−O) in the carboxyl group carries a slight negative charge, whereas the hydrogen bound to the nitrogen (N—H) in the amino group is slightly positive. This asymmetry of charge favors hydrogen bonding within the protein molecule itself and with other molecules contributing to both the structure and the function of many proteins. Before exploring the significance of such hydrogen bonds, it is necessary to examine the importance of the order of amino acids.

The primary structure of a protein is its amino acid sequence.

There are four levels of protein structure called primary, secondary, tertiary and quaternary. The precise sequence of amino acids in a polypeptide constitutes the primary structure of a protein. The peptide backbone of this primary structure consists of a repeating sequence of three atoms (—N—C—C—): the N from the amino group, the alpha-carbon, and the C from the carboxyl group of each amino acid. Scientists have deduced the primary structure of many proteins. The single-letter abbreviations for amino acids are used to record the amino acid sequence of a protein. Here, for example, are the first 20 amino acids (out of a total of 124) in the protein ribonuclease from a cow: KETAAAKFERQHMDSSTSAA

The theoretical number of different proteins is enormous. Since there are 20 different amino acids, there could be 20 x 20 = 400 distinct dipeptides (two linked amino acids) and 20 x 20 x 20 = 8,000 different tripeptides (three linked amino acids). Imagine this process of multiplying by 20 extended to a protein made up of 100 amino acids (which is considered a small protein). There could be 20100 such small proteins, each with its own distinctive primary structure. How large is the number 20100? There aren’t that many electrons in the entire universe. At the higher levels of protein structure, local coiling and folding give the molecule its final functional shape but all of these levels derive from the primary structure—that is, the precise location of specific amino acids in the polypeptide chain. The properties associated with a precise sequence of amino acids determine how the protein can twist and fold, thus adopting a specific stable structure that distinguishes it from every other protein. Primary structure is determined by covalent bonds. But the next level of protein structure is determined by weaker hydrogen bonds.

The secondary structure of a protein requires hydrogen bonding

A protein’s secondary structure consists of regular, repeated patterns in different regions of a polypeptide chain. There are two basic types of secondary structure, both of them determined by hydrogen bonding between the amino acid residues that make up the primary structure: a-helix and b-pleated sheet.

The a helix

The a (alpha) helix is a right-handed coil that is “threaded” in the same direction as a standard wood screw. The R groups extend outward from the peptide backbone of the helix. When this pattern of hydrogen bonding is established repeatedly over a segment of the protein, it stabilizes the coil resulting in a helix. The presence of amino acids with large R groups that distort the coil or otherwise prevent the formation of the necessary hydrogen bonds will keep a helix from forming. The helical secondary structure is common in the fibrous structural proteins called keratins, which make up hair, hooves and feathers. Hair can be stretched because stretching requires that only the hydrogen bonds of the helix, not the covalent bonds, be broken; when the tension on the hair is released, both the hydrogen bonds and the helix re-form.

The b (beta) pleated sheet.

A b (beta) pleated sheet is formed from two or more polypeptide chains that are almost completely extended and lying next to one another. The sheet is stabilized by hydrogen bonds between the N—H groups on one chain and the C−−O groups on the other (Figure). A pleated sheet may form between separate polypeptide chains, as in spider silk, or between different regions of the same polypeptide chain that is bent back on itself.

The tertiary structure of a protein is formed by bending and folding

In many proteins, the polypeptide chain is bent at specific sites and then folded back and forth, resulting in the tertiary structure of the protein. Although the helices and pleated sheets contribute to the tertiary structure, only parts of the macromolecule usually have these secondary structures and large regions consist of structures unique to a particular protein. While hydrogen bonding between the N—H and C−−O groups within and between chains is responsible for secondary structure, the interactions between R groups—the amino acid side chains—determine tertiary structure. Many of these interactions are involved in determining tertiary structure.

Covalent disulfide bridges can form between specific cysteine residues, holding a folded polypeptide in place. Hydrophobic side chains can aggregate together in the interior of the protein, away from water, folding the polypeptide in the process. Van der Waals forces can stabilize the close interactions between the hydrophobic residues. Ionic bonds can form between positively and negatively charged side chains buried deep within a protein, away from water forming a salt bridge. A complete description of a protein’s tertiary structure specifies the location of every atom in the molecule in three-dimensional space in relation to all the other atoms. The first tertiary structures to be determined took years to figure out but today, dozens of new structures are published every week. The major advances making this possible have been the ability to produce large quantities of specific proteins by biotechnology and the use of computers to analyze the atomic data. Bear in mind that both tertiary structure and secondary structure derive from a protein’s primary structure. If lysozyme is heated slowly, the heat energy will disrupt only the weak interactions and cause only the tertiary structure to break down. But the protein will return to its normal tertiary structure when it cools, demonstrating that all the information needed to specify the unique shape of a protein is contained in its primary structure.

The quaternary structure of a protein consists of subunits

As mentioned earlier, many functional proteins contain two or more polypeptide chains called subunits, each of them folded into its own unique tertiary structure. The protein’s quaternary structure results from the ways in which these subunits bind together and interact. Quaternary structure is illustrated by haemoglobin. Hydrophobic interactions, van der Waals forces, hydrogen bonds and ionic bonds all help hold the four subunits together to form the haemoglobin molecule. The function of hemoglobin is to carry oxygen in red blood cells. As hemoglobin binds one O2 molecule, four subunits shift their relative positions slightly, changing the quaternary structure. Ionic bonds are broken, exposing buried side chains that enhance the binding of additional O2 molecules. The structure changes again when hemoglobin releases its O2 molecules to the cells of the body.

The surfaces of proteins have specific shapes

Small molecules in a solution are in constant motion. They vibrate, rotate and move from place to place like corn in a popper. If two of them collide in the right circumstances, a chemical reaction can occur. The specific shapes of proteins allow them to bind noncovalently to other molecules that, in turn, allows other important biological events to occur.

Here are just a few examples:

Two adjacent cells can stick together because proteins protruding from each of the cells interact with each other.

A substance can enter a cell by binding to a carrier protein in the cell surface membrane.

A chemical reaction can be speeded up when an enzyme protein binds to one of the reactants. A “multi-protein machine,” DNA polymerase, can bind to and copy DNA. Another “multi-protein machine,” RNA polymerase, can synthesize RNA.

Chemical signals such as hormones can bind to proteins on a cell’s outer surface. Defensive proteins, called antibodies, can recognize the shape of a virus coat and bind to it. The biological specificity of protein function depends on two general properties of the protein: its shape and the chemistry of its exposed surface groups. When a molecule collides with and binds to a much larger protein, it is like a baseball being caught by a catcher’s mitt: the mitt has a shape that binds to the ball and fits around it. A hockey puck or a ping-pong ball would not fit a baseball catcher’s mitt. The binding of a molecule to a protein involves a general “fit” between two three-dimensional objects that becomes even more specific after initial binding.

Chemistry of proteins

The surface of a protein has certain chemical groups that it presents to a substance attempting to bind to it. These groups are the R groups of the exposed amino acids, and are therefore a property of the protein’s primary structure. Charged R groups can bind to oppositely charged groups on the ligand. Polar R groups containing a hydroxyl (—OH) group can form a hydrogen bond with the ligand. These three types of interactions—hydrophobic, ionic and hydrogen bonding—are weak by themselves but strong when all of them act together. Thus, the exposure of appropriate amino acid R groups on the protein surface allows the binding of a specific ligand to occur. Knowing the exact shape of a protein and what can bind to it is important not only in understanding basic biology but also in applied fields such as medicine. For example, the three-dimensional structure of a protease, a protein essential for the replication of HIV—the virus that causes AIDS—was first determined, then specific proteins were designed to bind to it and block its action. These protease inhibitors have prolonged the lives of countless people living with HIV.

Protein shapes are sensitive to the environment

Because it is determined by weak forces, protein shape is sensitive to environmental conditions that would not break covalent bonds, but do upset the weaker noncovalent interactions that determine secondary and tertiary structure. Increases in temperature cause more rapid molecular movements and thus can break hydrogen bonds and hydrophobic interactions. High concentrations of polar substances such as urea can disrupt the hydrogen bonding that is crucial to protein structure. Nonpolar solvents may also disrupt normal protein structure.

The loss of a protein’s normal three-dimensional structure is called denaturation and it is always accompanied by a loss of the normal biological function of the protein. Denaturation is often irreversible because amino acids that were buried may now be exposed at the surface and vice versa, causing a new structure to form or different molecules to bind to the protein. Boiling an egg denatures its proteins and is, as you know, not reversible. However, as we saw earlier in the case of lysozyme, denaturation may be reversible in the laboratory. If the protein is allowed to cool or the denaturing chemicals are removed, the protein may return to its “native” shape and normal function.

Chaperonins help shape proteins

There are two occasions when a polypeptide chain is in danger of binding the wrong ligand. First, following denaturation, hydrophobic R groups, previously on the inside of the protein away from water, become exposed on the surface. Since these groups can interact with similar groups on other molecules, the denatured proteins may aggregate and become insoluble, losing their function. Second, when a protein has just been made and has not yet folded completely, it can present a surface that binds the wrong molecule. In the cell, a protein can sometimes fold incorrectly as it is made. This can have serious consequences: In Alzheimer’s disease, misfolded proteins accumulate in the brain and bind to one another, forming fibers in the areas of the brain that control memory, mood and spatial awareness. Living systems limit inappropriate protein interactions by making a class of proteins called,appropriately, chaperonins (recall the chaperones—usually teachers—at school dances who try to prevent “inappropriate interactions” among the students). Chaperonins were first identified in fruit flies as “heat shock” proteins which prevented denaturing proteins from clumping together when the flies’ temperatures were raised. Some chaperonins work by trapping proteins in danger of inappropriate binding inside a molecular “cage”. This cage is composed of several identical subunits and is itself a good example of quaternary protein structure. Inside the cage, the targeted protein folds into the right shape, and then is released at the appropriate time and place.

Carbohydrates: Sugars and Sugar Polymers

The second class of biological molecules, the carbohydrates, is a diverse group of compounds. Carbohydrates contain primarily carbon atoms flanked by hydrogen atoms and hydroxyl groups (H—C—OH). They have two major biochemical roles:

They act as a source of energy that can be released in a form usable by body tissues.

They serve as carbon skeletons that can be rearranged to form other molecules that are essential for biological structures and functions.

Some carbohydrates are relatively small, with molecular weights of less than 100. Others are true macromolecules, with molecular weights in the hundreds of thousands. There are four categories of biologically important carbohydrates:

Monosaccharides (mono-, “one”; saccharide, “sugar”), such as glucose, ribose, and fructose, are simple sugars. They are the monomers out of which the larger carbohydrates are constructed.

Disaccharides (di-, “two”) consist of two monosaccharides linked together by covalent bonds.

Oligosaccharides (oligo-, “several”) are made up of several (3 to 20) monosaccharides.

Polysaccharides (poly-, “many”), such as starch, glycogen, and cellulose, are large polymers composed of hundreds or thousands of monosaccharides.

The general formula for carbohydrates, CH₂O, gives the relative proportions of carbon, hydrogen, and oxygen in a monosaccharide (i.e., the proportions of these atoms are 1:2:1). In disaccharides, oligosaccharides and polysaccharides, these proportions differ slightly from the general formula because two hydrogens and an oxygen are lost duringeach of the condensation reactions that form them.

Monosaccharides are simple sugars

Green plants produce monosaccharides through photosynthesis, and animals acquire them directly or indirectly from plants. All living cells contain the monosaccharide glucose. Cells use glucose as an energy source, breaking it down through a series of reactions that release stored energy and produce water and carbon dioxide. Glucose exists in two forms, the straight chain and the ring. The ring form predominates in more than 99 percent of circumstances because it is more stable under cellular conditions. Different monosaccharides contain different numbers of carbons. Most of the monosaccharides found in living systems belong to the D series of optical isomers. But some monosaccharides are structural isomers, which have the same kinds and numbers of atoms, but arranged differently. For example, the hexoses (hex-, “six”), a group of structural isomers, all have the formula C₆H₁₂O₆. Included among the hexoses are glucose, fructose (so named because it was first found in fruits), mannose and galactose. Pentoses (pent-, “five”) are five-carbon sugars. Some pentoses are found primarily in the cell walls of plants. Two pentoses are of particular biological importance: Ribose and deoxyribose form part of the backbones of the nucleic acids RNA and DNA, respectively. These two pentoses are not isomers; rather, one oxygen atom is missing from carbon 2 in deoxyribose (de-, “absent”). The absence of this oxygen atom has important consequences for the functional distinction of RNA and DNA.

Glycosidic linkages bond monosaccharides together

The disaccharides and polysaccharides described above are all constructed from monosaccharides that are covalently bonded together by condensation reactions that form glycosidic linkages. One such linkage between two monosaccharides forms a disaccharide. For example, a molecule of su-crose (table sugar) is formed from a glucose molecule and a fructose molecule, while lactose (milk sugar) contains glucose and galactose. The disaccharide maltose contains two glucose molecules but it is not the only disaccharide that can be made from two glucoses. Maltose and cellobiose are disaccharide isomers, both having the formula C₁₂H₂₂O₁₁. However, they are different compounds with different properties. They undergo different chemical reactions and are recognized by different enzymes. For example, maltose can be hydrolyzed to its monosaccharides in the human body, whereas cellobiose cannot. Certain microorganisms have the chemistry needed to break down cellobiose. Oligosaccharides contain several monosaccharides bound by glycosidic linkages at various sites. Many oligosaccharides have additional functional groups, which give them special properties. Oligosaccharides are often covalently bonded to proteins and lipids on the outer cell surface, where they serve as cell recognition signals. The human blood groups (such as ABO) get their specificity from oligosaccharide chains.

Polysaccharides serve as energy stores or structural materials

Polysaccharides are giant polymers of monosaccharides connected by glycosidic linkages. Starch is a polysaccharide of glucose. Glycogen is a highly branched polysaccharide of glucose. Starch actually comprises a large family of giant molecules of broadly similar structure. Some plant starches are unbranched, as in plant amylose; others are moderately branched, as in plant amylopectin. Starch readily binds water and when that water is removed, unbranched starch tends to form hydrogen bonds between the polysaccharide chains, which then aggregate. This is what causes bread to become hard and stale. Adding water and gentle heat separates the chains and the bread becomes softer. The polysaccharide glycogen stores glucose in animal livers and muscles. Starch and glycogen serve as energy storage compounds for plants and animals, respectively. These polysaccharides are readily hydrolyzed to glucose monomers, which in turn can be further degraded to liberate their stored energy and convert it to forms that can be used for cellular activities. If it is glucose that is actually needed for fuel, why must it be stored as a polymer? The reason is that 1,000 glucose molecules would exert 1,000 times the osmotic pressure of a single glycogen molecule. If it were not for polysaccharides, many organisms would expend a lot of time and energy expelling excess water. Cellulose is the predominant component of plant cell walls and is by far the most abundant organic (carbon-containing) compound on Earth. Starch can be easily degraded by the actions of chemicals or enzymes. Thus starch is a good storage medium that can be easily broken down to supply glucose for energy-producing reactions, while cellulose is an excellent structural material that can withstand harsh environmental conditions without changing.

Chemically modified carbohydrates contain other groups

Some carbohydrates are chemically modified by the addition of functional groups, such as phosphate and amino groups. For example, carbon 6 in glucose may be oxidized from —CH₂OH to a carboxyl group (—COOH), producing glucuronic acid. Or a phosphate group may be added to one or more of the —OH sites. Some of the resulting sugar phosphates, such as fructose 1,6-bisphosphate, are important intermediates in cellular energy reactions. When an amino group is substituted for an —OH group, amino sugars, such as glucosamine and galactosamine, are produced. These compounds are important in the extracellular matrix, where they form parts of proteins involved in keeping tissues together. Galactosamine is a major component of cartilage, the material that forms caps on the ends of bones and stiffens the protruding parts of the ears and nose. A derivative of glucosamine produces the polymer chitin, which is the principal structural polysaccharide in the skeletons of insects, crabs and lobsters, as well as in the cell walls of fungi. Fungi and insects (and their relatives) constitute more than 80 percent of the species ever described, and so chitin is one of the most abundant substances on Earth.

Lipids: Water-Insoluble Molecules

The lipids are a chemically diverse group of hydrocarbons. The property they all share is insolubility in water which is due to the presence of many nonpolar covalent bonds. Nonpolar hydrocarbon molecules are hydrophobic and preferentially aggregate among themselves, away from water, which is polar. When these nonpolar molecules are sufficiently close together, weak but additive van der Waals forces hold them together. These huge macromolecular aggregations are not polymers in a strict chemical sense, since their units (lipid molecules) are not held together by covalent bonds, as are, for example, the amino acids in proteins. But they can be considered polymers of individual lipid units. In this section, we will describe different types of lipids.

Lipids have a number of roles in living organisms:

· Fats and oils store energy.

· Phospholipids play important structural roles in cell membranes.

· The carotenoids help plants capture light energy.

· Steroids and modified fatty acids play regulatory roles as hormones and vitamins.

· The fat in animal bodies serves as thermal insulation.

· A lipid coating around nerves acts as electrical insulation.

· Oil or wax on the surfaces of skin, fur and feathers repels water.

Fats and oils store energy

Chemically, fats and oils are triglycerides, also known as simple lipids. Triglycerides that are solid at room temperature (20°C) are called fats; those that are liquid at room temperature are called oils. Triglycerides are composed of two types of building blocks: fatty acids and glycerol. Glycerol is a small molecule with three hydroxyl (—OH) groups (an alcohol). A fatty acid is made up of a long nonpolar hydrocarbon chain and a polar carboxyl group (—COOH). A triglyceride contains three fatty acid molecules and one molecule of glycerol. The carboxyl group of a fatty acid can form a covalent bond with the hydroxyl group of glycerol, resulting a functional group called an ester and water. The three fatty acids in a triglyceride molecule need notall have the same hydrocarbon chain length or structure: In saturated fatty acids, all the bonds between the carbon atoms in the hydrocarbon chain are single bonds— there are no double bonds. That is, all the bonds are saturated with hydrogen atoms. These fatty acid molecules are relatively rigid and straight and they pack together tightly, like pencils in a box.

In unsaturated fatty acids, the hydrocarbon chain contains one or more double bonds. Oleic acid, for example, is a monounsaturated fatty acid that has one double bond near the middle of the hydrocarbon chain, which causes a kink in the molecule. Some fatty acids have more than one double bond—are polyunsaturated— and have multiple kinks. These kinks prevent the molecules from packing together tightly. The kinks in fatty acid molecules are important in determining the fluidity and melting point of a lipid. The triglycerides of animal fats tend to have many long-chain saturated fatty acids, packed tightly together; these fats are usually solids at room temperature and have a high melting point. The triglycerides of plants, such as corn oil, tend to have short or unsaturated fatty acids. Because of their kinks, these fatty acids pack together poorly and have a low melting point, and these triglycerides are usually liquids at room temperature. Fats and oils are marvelous storehouses for energy. When they take in excess food, many animal species deposit fat droplets in their cells as a means of storing energy. Some plant species, such as olives, avocados, sesame, castor beans and all nuts, have substantial amounts of lipids in their seeds or fruits that serve as energy reserves for the next generation. This energy can be tapped by people who eat these plant oils or use them for fuel. Indeed, the famous German engineer Rudolf Diesel used peanut oil to power one of his early automobile engines in 1900.

Phospholipids form the core of biological membranes

Because lipids and water do not interact, a mixture of water and lipids forms two distinct layers. Many biologically important substances—such as ions, sugars, and free amino acids—that are soluble in water are insoluble in lipids.

Like triglycerides, phospholipids contain fatty acids bound to glycerol by ester linkages. In phospholipids, however, any one of several phosphate-containing compounds replaces one of the fatty acids. The phosphate functional group has a negative electric charge, so this portion of the molecule is hydrophilic, attracting polar water molecules. But the two fatty acids are hydrophobic, so they tend to aggregate away from water. In an aqueous environment, phospholipids line up in such a way that the nonpolar, hydrophobic “tails” pack tightly together and the phosphate-containing “heads” face outward, where they interact with water. The phospholipids thus form a bilayer, a sheet two molecules thick, with water excluded from the core. Biological membranes have this kind of phospholipid bilayer structure.

Carotenoids and steroids

The next two lipid classes we’ll discuss—the carotenoids and the steroids—have chemical structures very different from those of triglycerides and phospholipids and from each other. Both carotenoids and steroids are synthesized by covalent linking and chemical modification of isoprene to form a series of isoprene units.

Carotenoids trap light energy

The carotenoids are a family of light-absorbing pigments found in plants and animals. Beta-carotene is one of the pigments that traps light energy in leaves during photosynthesis. In humans, a molecule of beta-carotene can be broken down into two vitamin A molecules, from which we make the pigment rhodopsin, which is required for vision. Carotenoids are responsible for the colors of carrots, tomatoes, pumpkins, egg yolks and butter.

Steroids are signal molecules

The steroids are a family of organic compounds whose multiple rings share carbons. The steroid cholesterol is an important constituent of membranes. Other steroids function as hormones, chemical signals that carry messages from one part of the body to another. Testosterone and the estrogens are steroid hormones that regulate sexual development in vertebrates. Cortisol and related hormones play many regulatory roles in the digestion of carbohydrates and proteins, in the maintenance of salt balance and water balance and in sexual development. Cholesterol is synthesized in the liver and is the starting material for making testosterone and other steroid hormones, as well as the bile salts that help break down dietary fats so that they can be digested. Cholesterol is absorbed from foods such as milk, butter and animal fats.

Some lipids are vitamins

Vitamins are small molecules that are not synthesized by the body, but are necessary for its normal functioning. Vitamins must be acquired from dietary sources.

Vitamin A is formed from the beta-carotene found in green and yellow vegetables. In humans, a deficiency of vitamin A leads to dry skin, eyes and internal body surfaces, retarded growth and development and night blindness, which is a diagnostic symptom for the deficiency.

Vitamin D regulates the absorption of calcium from theintestines. It is necessary for the proper deposition of calcium in bones; a deficiency of vitamin D can lead to rickets, a bone-softening disease.

Vitamin E seems to protect cells from the damaging effects of oxidation–reduction reactions. For example, it has an important role in preventing unhealthy changes in the double bonds in the unsaturated fatty acids of membrane phospholipids. Commercially, vitamin E is added to some foods to slow spoilage.

Vitamin K is found in green leafy plants and is also synthesized by bacteria normally present in the human intestine. This vitamin is essential to the formation of blood clots. Inadequate vitamin intake can lead to deficiency diseases.

Wax coatings repel water

The sheen on human hair is not there only for cosmetic purposes. Glands in the skin secrete a waxy coating that repels water and keeps the hair pliable. Birds that live near water have a similar waxy coating on their feathers. The shiny leaves of holly plants, familiar during winter holidays, also have a waxy coating. Finally, bees make their honeycombs out of wax. All waxes have the same basic structure: They are formed by an ester linkage between a saturated, long-chain fatty acid and a saturated, long-chain alcohol. The result is a very long molecule, with 40–60 CH₂ groups. For example, here is the structure of beeswax: This highly nonpolar structure accounts for the impermeability of wax to water.

Nucleic Acids: Informational and Catalytic Macromolecules

The nucleic acids are polymers specialized for the storage, transmission, and use of information. There are two types of nucleic acids: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). DNA molecules are giant polymers that encode hereditary information and pass it from generation to generation. Through an RNA intermediate, the information encoded in DNA is also used to specify the amino acid sequence of proteins. Information flows from DNA to DNA in reproduction, but in the nonreproductive activities of the cell, information flows from DNA to RNA to proteins which ultimately carry out these functions. In addition, certain RNAs act as catalysts for important reactions in cells.

The nucleic acids have characteristic chemical properties

Nucleic acids are composed of monomers called nucleotides, each of which consists of a pentose sugar, a phosphate group, and a nitrogen-containing base—either a pyrimidine or a purine. (Molecules consisting of a pentose sugar and a nitrogenous base, but no phosphate group, are called nucleosides.) In DNA, the pentose sugar is deoxyribose, which differs from the ribose found in RNA by one oxygen atom. In both RNA and DNA, the backbone of the macromolecule consists of alternating pentose sugars and phosphates (sugar—phosphate—sugar—phosphate). The bases are attached to the sugars and project from the chain. The nucleotides are joined by phosphodiester linkages between the sugar of one nucleotide and the phosphate of the next (-diester refers to the two covalent bonds formed by —OH groups reacting with acidic phosphate groups). The phosphate groups link carbon 3 in one pentose sugar to carbon 5 in the adjacent sugar. Most RNA molecules consist of only one polynucleotide chain. DNA, however, is usually double-stranded; it has two polynucleotide strands held together by hydrogen bonding between their nitrogenous bases. The two strands of DNA run in opposite directions. This antiparallel orientation is necessary for the strands to fit together in three-dimensional space.

The uniqueness of a nucleic acid resides in its nucleotide sequence

Only four nitrogenous bases—and thus only four nucleotides— are found in DNA. The DNA bases and their abbreviations are adenine (A), cytosine (C), guanine (G), and thymine (T). A key to understanding the structure and function of nucleic acids is the principle of complementary base pairing. In double-stranded DNA, adenine and thymine always pair (A-T), and cytosine and guanine always pair (C-G). Base pairing is complementary because of three factors: the sites for for hydrogen bonding on each base, the geometry of the sugar–phosphate backbone, which brings opposite bases near each other, and the molecular sizes of the paired bases. Adenine and guanine are both purines consisting of two fused rings. Thymine and cytosine are both pyrimidines, consisting of only one ring. The pairing of a large purine with a small pyrimidine ensures stability and consistency in the double-stranded molecule of DNA. Ribonucleic acids are also made up of four different monomers, but their nucleotides differ from those of DNA. In RNA the nucleotides are termed ribonucleotides (the ones in DNA are deoxyribonucleotides). They contain ribose rather than deoxyribose, and instead of the base thymine, RNA uses the base uracil (U). The other three bases are the same as in DNA. Although RNA is generally single-stranded, complementary hydrogen bonding between ribonucleotides can take place. These bonds play important roles in determining the shapes of some RNA molecules and in associations between RNA molecules during protein synthesis. When the base sequence of DNA is copied in the synthesis of RNA, complementary base pairing also takes place between ribonucleotides and deoxyribonucleotides. In RNA, guanine and cytosine pair (G-C), as in DNA, but adenine pairs with uracil (A-U). Adenine in an RNA strand can pair either with uracil (in another RNA strand) or with thymine (in a DNA strand).

DNA is a purely informational molecule. The information in DNA is encoded in the sequence of bases carried in its strands—the information encoded in the sequence TCAG is different from the information in the sequence CCAG. The information can be read easily and reliably, in a specific order. The three-dimensional appearance of DNA is strikingly uniform. The variations in DNA—the different sequences of bases—are strictly “internal.” Through hydrogen bonding, two complementary polynucleotide strands pair and twist to form a double helix. When compared with the complex and varied tertiary structures of different proteins, this uniformity is surprising. But this structural contrast makes sense in terms of the functions of these two classes of macromolecules. It is their different and unique shapes that permit proteins to recognize specific “target” molecules. The unique threedimensional form of each protein matches at least a portion of the surface of the target molecule. In other words, structural diversity in the molecules to which proteins bind requires corresponding diversity in the structure of the proteins themselves. In DNA, then, the information is in the sequence of the bases; in proteins, the information is in the shape of the molecule.

Because DNA carries hereditary information between generations, a theoretical series of DNA molecules with changes in base sequences stretches back through evolutionary time. Closely related living species should have more similar base sequences than species judged by other criteria to be more distantly related. The examination of base sequences has confirmed many of the evolutionary relationships that have been inferred from the more traditional study of body structures, biochemistry, and physiology. For example, the closest living relative of humans (Homo sapiens) is the chimpanzee (genus Pan), which shares more than 98 percent of its DNA base sequence with human DNA. This confirmation of well-established evolutionary relationships gives credibility to the use of DNA to elucidate relationships when studies of structure are not possible or are not conclusive. For example, DNA studies revealed a close evolutionary relationship between starlings and mockingbirds that was not expected on the basis of their anatomy or behavior. DNA studies support the division of the prokaryotes into two domains, Bacteria and Archaea. Each of these two groups of prokaryotes is as distinct from the other as either is from the Eukarya, the third domain into which living things are classified. In addition, DNA comparisons support the hypothesis that certain subcellular compartments of eukaryotes (the organelles called mitochondria and chloroplasts) evolved from early bacteria that established a stable and mutually beneficial way of life inside larger cells.

RNA may have been the first biological catalyst

The three-dimensional structure of a folded RNA molecule presents a unique surface to the external environment. These surfaces are every bit as specific as those of proteins. We noted above that an important role of proteins in biology is to act as catalysts, speeding up reactions that would ordinarily take place too slowly to be biologically useful, and that the spatial property of proteins is vital to this role. As we will see, certain RNA molecules can also act as catalysts, using their three-dimensional shapes and other chemical properties. They can catalyze reactions on their own nucleotides as well as in other cellular substances. These catalytic RNAs are called ribozymes. Their discovery had implications for theories of the origin of life. Organisms can synthesize both RNA and proteins from these monomers. As we noted above, in current organisms on the Earth, protein synthesis requires DNA and RNA, and nucleic acid synthesis requires proteins (as enzymes). The discovery of catalytic RNAs led to the hypothesis that early life was part of an “RNA world.” RNA can be informational (in its nucleotide sequence) as well as catalytic. So when RNA was first made, it could have acted as a catalyst for its own replication, as well as for the synthesis of proteins. Then DNA could have eventually evolved by being made from RNA. There is some laboratory evidence supporting this scenario: RNAs of different sequences have been put in a test tube and made to replicate on their own. Such self-replicating ribozymes speed up the synthesis of RNA 7 million-fold. In living organisms today, the formation of peptide linkages is catalyzed by a ribozyme. In certain viruses called retroviruses, there is an enzyme called reverse transcriptase that catalyzes the synthesis of DNA from RNA.

Nucleotides have other important roles

Nucleotides are more than just the building blocks of nucleic acids. As we will see in later chapters, there are several nucleotides with other functions: ATP (adenosine triphosphate) acts as an energy transducer in many biochemical reactions.

GTP (guanosine triphosphate) serves as an energy source, especially in protein synthesis. It also has a role in the transfer of information from the environment to the body tissues. CAMP (cyclic adenosine monophosphate), a special nucleotide in which a bond forms between the sugar and phosphate groups within adenosine monophosphate, is essential in many processes, including the actions of hormones and the transmission of information by the nervous system.

All Life from Life

The concepts conveyed throughout this chapter—that large molecules obey the mechanistic laws of physics and chemistry, and that life could have arisen from inanimate, self-replicating macromolecules—have come to be generally accepted by the scientific community. So should we expect to see new life forms arise at any time from the biochemical environment? During the Renaissance (a period from about 1350 to 1700 A.D., marked by the birth of modern science), most people thought that at least some forms of life arose directly from inanimate or decaying matter by spontaneous generation. For instance, it was suggested that mice arose from sweaty clothes placed in dim light, frogs came from moist soil, and flies were produced from meat. These ideas were attacked by scientists such as the Italian doctor and poet Francisco Redi using the relatively new idea of using experiments to test an idea. In 1668, Redi proposed that flies arose not by some mysterious transformation of decaying meat but from other flies, who laid their eggs on the meat. The eggs developed into wormlike maggots (the immature form of flies). Redi set out several jars containing chunks of meat. One jar contained meat exposed both to the air and to flies.

A second jar contained meat in a container wrapped in a fine cloth so that the meat was exposed to the air, but not to flies. The meat in the third jar was in a sealed container and thus was not exposed to either air or flies. As he had hypothesized, Redi found maggots, which then hatched into flies, only in the first container. The idea that a complex organism like a fly could come from a totally different substance was laid to rest. With the invention of the microscope in the 1660s, a vast new biological world was unveiled. Under microscopic observation, virtually every environment on Earth was found to be teeming with tiny organisms such as bacteria. Some scientists believed that these organisms arose spontaneously from their rich chemical environment. The experiments that disproved this idea were done by the great French scientist Louis Pasteur. His experiments showed that microorganisms come only from other microorganisms and that an environment without life remains lifeless unless contaminated by living creatures. These experiments by Redi, Pasteur and others provided solid evidence that neither small (bacteria) nor large (flies) organisms come from inanimate matter, but instead come from living parent organisms. Indeed, life on Earth no longer arises from nonliving materials. This is because the atmospheric and planetary conditions that exist on Earth today are vastly different from those on the prebiotic, anaerobic planet. The oxygen present in today’s atmosphere would break down the prebiotic molecules before they could accumulate. In addition, the necessary energy sources—including constant lightning strikes, immense volcanic eruptions and bombardment by intense ultraviolet light—are no longer present with anything like their primeval force.

Life may have come from outside Earth. The evidence for this proposal comes primarily from chemicals contained in meteorites that have landed on Earth. The theory of chemical evolution proposes that life on Earth originated on the Earth. Experiments using model systems that attempt to duplicate the ancient Earth have shown that chemical evolution could have produced the four types of macromolecules that distinguish living things.

Macromolecules are polymers constructed by the formation of covalent bonds between smaller molecules called monomers. Macromolecules in living organisms include polysaccharides, proteins, and nucleic acids. Macromolecules have specific, characteristic three-dimensionalshapes that depend on the structure, properties, and sequence of their monomers. Different functional groups give local sites on macromolecules specific properties that are important for their biological functioning and their interactions with other macromolecules.

Monomers are joined by condensation reactions, which release a molecule of water for each bond formed. Hydrolysis reactions use water to break polymers into monomers.

The functions of proteins include support, protection, catalysis, transport, defense, regulation, and movement. Protein function sometimes requires an attached prosthetic group. There are 20 amino acids found in proteins. Each amino acid consists of an amino group, a carboxyl group, a hydrogen and a side chain bonded to the carbon atom. The side chains or R groups of amino acids may be charged polar or hydrophobic; there are also special cases, such as the —SH groups of cysteine, which can form disulfide bridges. The side chains give different properties to each of the amino acids.

Amino acids are covalently bonded together into polypeptide chains by peptide linkages, which form by condensation reactions between the carboxyl and amino groups. Polypeptide chains are folded into specific three-dimensional shapes to form functional proteins. Four levels of protein structure are possible: primary, secondary, tertiary and quaternary. The primary structure of a protein is the sequence of amino acids bonded by peptide linkages. This primary structure determines both the higher levels of structure and protein function. The two types of secondary structure a-helices and b-pleated sheets—are maintained by hydrogen bonds between atoms of the amino acid residues. The tertiary structure of a protein is generated by bending and folding of the polypeptide chain. The quaternary structure of a protein is the arrangement of two or more polypeptides into a single functional protein consisting of two or more polypeptide subunits. Weak chemical interactions are important in the three-dimensional structure of proteins and in their binding to other molecules. Proteins denatured by heat, alterations in pH or certain chemicals lose their tertiary and secondary structure as well as their biological function. Renaturation is not often possible. Chaperonins assist protein folding by preventing binding to inappropriate ligands.

All carbohydrates contain carbon bonded to hydrogen atoms and hydroxyl groups. Hexoses are monosaccharides that contain six carbon atoms. Examples of hexoses include glucose, galactose, and fructose, which can exist as chains or rings. The pentoses are five-carbon monosaccharides. Two pentoses, ribose and deoxyribose, are components of the nucleic acids RNA and DNA, respectively. They covalently link monosaccharides into larger units such as disaccharides, oligosaccharides, and polysaccharides. Cellulose, a very stable glucose polymer, is the principal component of the cell walls of plants. Starches, less dense and less stable than cellulose, store energy in plants. Chemically modified monosaccharides include the sugar phosphates and amino sugars. A derivative of the amino sugar glucosamine polymerizes to form the polysaccharide chitin which is found in the cell walls of fungi and the exoskeletons of insects.

Although lipids can form gigantic structures, these aggregations are not chemically macromolecules because the individual units are not linked by covalent bonds. Fats and oils are triglycerides, composed of three fatty acids covalently bonded to a glycerol molecule by ester linkages. Saturated fatty acids have a hydrocarbon chain with no double bonds. The hydrocarbon chains of unsaturated fatty acids have one or more double bonds that bend the chain, making close packing less possible. Phospholipids have a hydrophobic hydrocarbon “tail” and a hydrophilic phosphate “head.” In water, the interactions of the hydrophobic tails and hydrophilic heads of phospholipids generate a phospholipids bilayer that is two molecules thick. The head groups are directed outward, where they interact with the surrounding water. The tails are packed together in the interior of the bilayer. Carotenoids trap light energy in green plants. Carotene can be split to form vitamin A, a lipid vitamin. Some steroids, such as testosterone, function as hormones. Cholesterol is synthesized by the liver and has a role in cell membranes, as well as in the digestion of fats. Vitamins are substances that are required for normal functioning, but must be acquired from the diet.

DNA is the hereditary material. Both DNA and RNA play roles in the formation of proteins. Information flows from DNA to RNA to protein. Nucleic acids are polymers made up of nucleotides. A nucleotide consists of a phosphate group, a sugar (ribose in RNA and deoxyribose in DNA), and a nitrogen-containing base. In DNA the bases are adenine, guanine, cytosine, and thymine, but in RNA uracil substitutes for thymine. In the nucleic acids, the bases extend from a sugar–phosphate backbone. The information content of DNA and RNA resides in their base sequences. RNA is single-stranded. DNA is a double stranded helix in which there is complementary, hydrogenbonded base pairing between adenine and thymine (A-T) and guanine and cytosine (G-C). The two strands of the DNA doublehelix run in opposite directions. Base pairing of single-stranded RNAs can lead to three-dimensional Base pairing of single-stranded RNAs can lead to threedimensional structures, which can be catalytic. This finding has led to the proposal that in the origin of life, RNA preceded protein. Comparing the DNA base sequences of different livi

Date: 2014-12-22; view: 912