3: Macromolecules: Their Chemistry and Biology

Macromolecules: Giant Polymers

· There are four major types of biological macromolecules: proteins, carbohydrates, lipids, and nucleic acids.

· These macromolecules are made the same way in all living things, and they are present in all organisms in roughly the same proportions.

· They make up what we visually recognize as life.

· Macromolecules are giant polymers. Poly means many; mer means units.

· Polymers are formed by covalent linkages of smaller units called monomers; mono means single.

· Molecules with molecular weights greater than 1,000 daltons (atomic mass units) are usually classified as macromolecules.

· Some of the roles of macromolecules are

· Energy storage

· Structural support

· Catalysis

· Transport

· Protection and defense

· Regulation of metabolic activities

· Maintenance of homeostasis

· Means for movement, growth, and development

· Heredity

· The functions of macromolecules are related to their shape and the chemical properties of their monomers.

· Proteins fold based on their primary composition to generate functional structures such as catalysts or strong flexible fibers like those found in spider webs.

· Carbohydrates (sugars) link to form cellulose, the wood fiber of trees, or starches for storing energy.

· Proteins form long, thin assemblies that can contract and cause movement.

· Some types of macromolecules contain many different kinds of monomers.

· Some contain the same simple units, repeated many times.

Condensation Reactions

· Macromolecules are made from smaller monomers by removing an OH from one monomer and an H from another monomer to link them together. (See Figure 3.2.) This is called a condensation or dehydration (loss of water) reaction.

· Energy must be added to make or break a polymer.

· The reverse reaction, breaking polymers back into monomers, is a hydrolysis reaction (hydro means water; lysis, break).

· A hydrolysis reaction is one in which water is added and reacts with the bond that links the units together.

· It takes special proteins, called enzymes, to make polymers from monomers.

· Most hydrolysis in biological systems is also performed by enzymes, although a strong acid or base solution can hydrolyze many types of polymers.

· In people, stomach acid hydrolyzes some of the linkages found in the polymers we eat.

Proteins: Polymers of Amino Acids

· Proteins are molecules with diverse structure and function.

· Proteins have important roles in:

· Structural support

· Protection

· Catalysis

· Transport

· Defense

· Regulation

· Movement

· Proteins called enzymes are particularly important in biological systems. Enzymes increase the rates of chemical reactions in cells. This function is known as catalysis.

· Enzymes are highly specific; in general, each enzyme catalyzes only one chemical reaction.

· Proteins range in size from a few amino acids to thousands.

· Some proteins are composed of a single chain of amino acids, called a polypeptide.

· Other proteins have more than one polypeptide chain.

· Folding is crucial to the function of a protein. Folding is influenced largely by the sequence of amino acids.

· Each different type of protein has a characteristic amino acid composition and order.

· Some proteins have additional, non-amino acid chemical structures called prosthetic groups. These groups include carbohydrates, lipids, phosphate groups, ion-containing heme groups, metal ions, and others.

Proteins are composed of amino acids

· The amino group is the nitrogen-containing part (NH₃⁺).

· The acid is a carboxyl group (COO^–)

· Differences in amino acids come from the side chains, or the R groups, found attached to the same carbon as the amino group. (See Table 3.2.)

· The 20 common amino acids vary widely in properties.

· All but one have four different groups that are attached to the a carbon.

· A hydrogen atom, an amino group, and a carboxyl group are bonded to the a carbon of all the different amino acids.

· The fourth group, the R group, is what makes one type of amino acid different from another.

· Glycine has H as its R group and is, therefore, the only amino acid that has three rather than four groups attached to the a carbon.

· Carbons with four different groups attached can exist in different stereoisomeric forms. All amino acids do, except for glycine.

· Amino acids can be classified based on the characteristics of their R groups.

· Five of the 20 amino acids form ions in solution depending on pH.

· Four of the 20 have polar side chains.

· Eight have nonpolar R groups.

· Three amino acids, cysteine, glycine, and proline, have some special properties.

· Cysteine has a terminal disulfide (—S—S—). (See Figure 3.3.)

· Glycine has a hydrogen atom as the side chain. This group is small enough to fit into small spaces and tight corners when the protein folds.

· Proline has a modified amino group that forms a covalent bond with the R group.

· Proline's ring limits rotation of the a carbon’s bond.

· Proline is often found at bends and loops of proteins.

Peptide linkages covalently bond amino acids together

· Proteins are synthesized by condensation reactions between the amino group of one amino acid and the carboxyl group of another. This forms a peptide linkage. (See Figure 3.4.)

· Proteins are also called polypeptides. A dipeptide is two amino acids long; a tripeptide, three. A polypeptide is multiple amino acids long.

· The first amino acid of a peptide is called the N-terminus amino acid because the amino group is free, or unbound.

· The last is called the C-terminus amino acid and has a free carboxyl group.

· The C–N peptide linkage forms a partial double bond, which is a single covalent and polar attraction. This bond limits folding and restricts the ability of the adjacent atoms to rotate.

· Within the central axis of the protein, there is an asymmetry of charge favoring a tendency toward hydrogen bonding. (Oxygen is partially negative and nitrogen is slightly positive.)

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

· There are four levels of protein structure: primary, secondary, tertiary, and quaternary. (See Figure 3.5.)

· The precise sequence of amino acids is called its primary structure.

· The peptide backbone is repeating units of atoms: N—C—C—N—C—C…

· In the figure, the portion on the left is the N terminus; on the right is the C terminus.

· The protein is synthesized starting from the N terminus and adding to the C terminus.

· Many proteins have now been sequenced.

· The two conventions for representing the sequence are three-letter and one-letter systems. (See Table 3.2.)

· In the three-letter system, methionine is Met; in the one-letter system, it is M.

· Amazing numbers of different proteins are possible.

· With 20 amino acids, 400 different dipeptides are possible (20 ´ 20 = 400). One would be glycine—glycine, another would be glycine—methionine.

· There are 20¹⁰⁰ different possible proteins that are made up of just 100 amino acids. Proteins can also be made up of fewer or greater than 100 amino acids, which makes the number of different proteins mind-boggling.

The secondary structure of a protein requires hydrogen bonding

· Secondary structure is the shape regions of the peptide take on as a folded polymer.

· This shape is influenced primarily by the amino acid sequence (the primary structure).

· There are two common secondary structures.

· One is the a helix, a right-handed coil. (See Figure 3.5b.)

· The peptide backbone takes on the helical shape due to hydrogen bonds.

· The R groups point away from the peptide backbone.

· Large R groups tend to prevent the creation of this structure.

· Insoluble fibrous structural proteins have a-helical secondary structures. Examples are the proteins found in hair, feathers, and hooves, called keratins.

· Hair stretches because only hydrogen bonds, not covalent bonds, are broken when it is pulled.

· Another common secondary structure is b pleated sheets.

· These form from peptide regions that lie parallel to each other. (See Figure 3.5c.)

· Sometimes the parallel regions are in the same peptide.

· Sometimes the parallel regions are from different peptide strands.

· This sheetlike structure is stabilized by hydrogen bonds between N—H groups on one chain with the C=O group on the other.

· Spider silk is made of b pleated sheets from separate peptides. Despite the weakness of the hydrogen bonds, together they tend to be additive; therefore, substances like spider silk can be remarkably strong.

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

· Tertiary structure is the three-dimensional shape of the completed polypeptide. (See Figure 3.5d.)

· The primary determinant of the tertiary structure is the interaction between R groups, which is determined by the protein’s primary structure.

· Other factors are

· The nature and location of secondary structures

· The location of disulfide bridges, which form between cysteine residues

· Hydrophobic side chain aggregation and van der Waals forces, which help stabilize them

· The ionic interactions, the positive and negative charges deep in the protein away from water

The quaternary structure of a protein consists of subunits

· Some proteins are composed of subunits, which are separate peptide chains that associate together to create the functional protein. (See Figure 3.5e.)

· This dimension is called the quaternary structure, and it adds to the 3-D shape of the finished protein.

· Quaternary structure results from the ways in which multiple polypeptide subunits bind together and interact.

· Hemoglobin is an example of such a protein; it has four subunits. (See Figure 3.7.)

The surfaces of proteins have specific shapes

· Shape is crucial to the functioning of some proteins.

· An enzyme must bind substrates correctly, and the correct surface shape allows for that.

· Examples are carrier proteins in the cell surface membrane, ribosomes, which synthesize proteins, and the binding of chemicals (hormones) to a cell surface membrane.

· Cells in tissues snap together and are held by the complementary shapes.

· Multicomponent proteins are held together by their shape, charges, hydrophobic properties, and, occasionally, disulfide bonds.

· Hormones bind to receptor proteins because of the protein’s shape. The shape of the bound protein must change precisely in response to the hormone binding.

· It is the combination of attractions, repulsions, and interactions that determines the right fit. (See Figure 3.8.)

Protein shapes are sensitive to the environment

· Changes in temperature, pH, salt concentrations, and oxidation or reduction conditions can change the shape of proteins. This process is called denaturation. (See Figure 3.9.)

· Often denaturation is irreversible, like the boiling of egg white.

· Some chemically induced changes are reversed by removal of the chemical condition that caused them.

· A few proteins, like ribonuclease, resist denaturation; they can be boiled for days and retain activity once cooled.

Chaperonins help shape proteins

· Chaperonins are specialized proteins that help keep other proteins from interacting inappropriately with each other prior to positioning.

· Some chaperonins help folding, some prevent folding until the appropriate time. (See Figure 3.10.)

Carbohydrates: Sugars and Sugar Polymers

· Carbohydrates are carbon molecules with hydrogen and hydroxyl groups.

· They act as energy storage and transport molecules.

· They also serve as structural components.

· Carbohydrate monomers have molecular weights of approximately 100 daltons.

· Polymers composed of monomers can have molecular weights of up to hundreds of thousands of daltons.

· There are four major categories of carbohydrates:

· Monosaccharides

· Disaccharides, which consist of two monosaccharides

· Oligosaccharides, which consist of between 3 and 20 monosaccharides

· Polysaccharides, which are composed of hundreds to hundreds of thousands of monosaccharides

· The general formula for a carbohydrate monomer is multiples of CH₂O, maintaining a ratio of 1 carbon to 2 hydrogens to 1 oxygen.

· During the polymerization, which is a condensation reaction, water is removed. As a result, the carbohydrate polymers have ratios of carbon, hydrogen, and oxygen that differ somewhat from the 1:2:1 ratios of the monomers.

Monosaccharides are simple, single sugars

· All living cells contain glucose (C₆H₁₂O₆).

· Green plants produce monosaccharides; other organisms acquire glucose, or the energy to make it, from plants.

· Cells break down glucose to release energy, with the final products being carbon dioxide and water.

· Glucose exists as a straight chain and a ring. (See Figure 3.11.)

· The ring form is predominant (>99%). There are two forms of the ring: a-glucose and b-glucose.

· The two forms exist in equilibrium when dissolved in water.

· Different monosaccharides have either different numbers or arrangements of carbons. (See Figure 3.12.)

· Most monosaccharides are optical isomers.

· Hexoses (six-carbon sugars) include the following structural isomers: glucose, fructose, mannose, and galactose.

· Two examples of pentoses (five-carbon sugars) are ribose and deoxyribose, which make up the backbones of nucleic acids (RNA and DNA).

· These pentoses are not isomers. Deoxyribose is missing an oxygen atom at carbon 2. This results in a functional distinction between DNA and RNA.

Glycosidic linkages bond monosaccharides together

· Glycosidic linkages are created by enzymes and are condensation reactions.

· Disaccharides have just one such linkage.

· Sucrose (table sugar) is glucose bonded to a fructose.

· Lactose (milk sugar) is glucose bonded to a galactose.

· Maltose has two a-linked glucose molecules.

· Cellobiose also has two glucose molecules, but they are b-linked.

· Figure 3.13 shows the two possible glycosidic linkages.

· Maltose and cellobiose have the same chemical formula but are structural isomers.

· The shape difference changes the biological nature of the molecules.

· Enzymes that break down maltose fail to break down cellobiose.

· Humans can break down maltose, but not cellobiose.

· Oligosaccharides contain more than two monosaccharides.

· Many proteins found on the outer surface of cells have oligosaccharides attached to the R group of certain amino acids, or to lipids.

· The human ABO blood types owe their specificity to oligosaccharide chains.

Polysaccharides serve as energy stores or structural materials

· Polysaccharides are giant chains of monosaccharides connected by glycosidic linkages.

· Cellulose is a giant polymer of glucose alone joined by b-1,4 linkages. (See Figure 3.14.)

· Starch is a polysaccharide of glucose with a-1,4 linkages.

· Starch can be readily degraded by the action of chemicals or enzymes, making it a good storage medium.

· Cellulose is much more stable chemically than starch and more difficult to hydrolyze chemically and enzymatically. This quality makes it an excellent structural material.

· Starches vary by amount of branching. (See Figure 3.14.)

· Plant starch, called amylose, is slightly branched.

· Animal starch, called glycogen, is highly branched.

· Starches are molecules that store glucose.

· Each polymer molecule has essentially the same effect as one monomer molecule on the osmotic pressure of a solution.

· Combining many glucose molecules into just one reduces the osmotic effect, allowing storage of lots of energy, without disturbing the water content of a cell too much.

Chemically modified carbohydrates contain other groups

· The addition of functional groups modifies carbohydrates. (See Figure 3.15.)

· Glucose can oxidize to acquire a carboxyl group (—COOH), producing glucuronic acid.

· Phosphate is enzymatically added to one or more of the hydroxyl (—OH) sites, creating a sugar phosphate such as fructose 1,6-bisphosphate.

· Amino groups can be substituted for an —OH, making an amino sugar such as glucosamine and galactosamine.

· Amino sugars are important to the extracellular matrix, the systems that hold tissues together.

· Galactosamine is a major component of cartilage, which is found in your ears, nose, and kneecaps.

· A glucosamine derivative is a component of chitin, the polysaccharide in the skeletons of insects, prawns, and crabs. It is also found in the cell walls of fungi. Chitin is one of the most abundant substances on earth.

Nucleic Acids: Informational Macromolecules

· Nucleic acid polymers are linearly arranged information molecules.

· Two types of nucleic acid polymers are DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

· The DNA molecules of humans are enormous polymers that encode hereditary information bound in nucleotides.

· More than 130 million nucleotides are found in just one human chromosome of average length.

· In nonreproductive cell activities, information stored in DNA is transferred to RNA molecules.

· The average length of an RNA molecule, although occasionally thousands of bases in length, is much shorter than a DNA molecule.

· A DNA molecule contains information necessary for the production of many different RNA molecules. DNA molecules can code for RNA molecules repeatedly over the life of a cell.

· The information in RNA molecules is decoded to specify the sequence of amino acids in proteins.

The nucleic acids have characteristic structures and properties

· DNA differs from RNA due to the absence of the oxygen in the 2-carbon position of the ribose.

· DNA typically is double-stranded: Two separate polymer chains are associated together. The association is not haphazard, but complementary.

· At each position where a purine is found on one strand, a pyrimidine is found on the other.

· Purines have a fused double-ring structure.

· Pyrimidines have just one ring.

· Pairing of a purine with a pyrimidine maintains three rings in the center of the molecule, so the backbones of the two strands maintain a constant distance along the length of the double-stranded molecule.

· DNA and RNA polymers are enzymatically made and, like all the other polymers mentioned so far, are created with condensation reactions.

· The linkages that hold the nucleotides in the polymer are called phosphodiester linkages. (See Figure 3.17.)

· These linkages are formed between carbon 3 of the sugar (ribose in RNA, deoxyribose in DNA) and a phosphate group that is associated with carbon 5 of the sugar.

· The backbone consists of alternating sugars and phosphates.

· In DNA, the two strands are antiparallel: Looking at one end, one strand ends with a free carbon 5 of the deoxyribose, the other with a carbon 3 of the deoxyribose.

· The two strands are held together by the attractions formed by nitrogenous bases in the center of the double-stranded molecule.

· The attractions are hydrogen bonds that form due to partial positive and negative charges, as described in Chapter 2.

· Most RNA molecules consist of only a single polynucleotide chain.

The uniqueness of a nucleic acid resides in its base sequence

· The main principle is complementary base pairing by hydrogen bond formation.

· Only four different DNA bases are found in DNA.

· They are adenine (A), cytosine (C), guanine (G), and thymine (T).

· Where an A is found on one strand, a T is found at the same point in the complementary strand.

· Wherever a G is found on one strand, a C is found on the other.

· It is between these bases that hydrogen bonds form, linking the two complementary strands.

· DNA complementary strands form a double helix, a molecule with a right-hand twist.

· DNA is an information molecule and serves no other purpose. The information is stored in the order of the four different bases.

· This order is transferred to RNA molecules, which are used to direct the order of the amino acids in proteins.

· There are three main structural differences between DNA and RNA:

· RNA has ribose, which has oxygen at carbon 2 of the sugar.

· Instead of having thymine, RNA molecules have uracil.

· RNA is single-stranded.

· RNA is crucial for information storage and transmission, but unlike DNA, some RNA molecules may have another function: RNA polymers with enzymatic activity similar to proteins have been discovered. These RNA molecules are called ribozymes.

· DNA molecules have a much more uniform shape than the proteins they code for. The uniform shape of DNA molecules makes it easy to “read” the information they contain. This information is used to make a multitude of proteins, whose functions are related to their diverse shapes.

DNA is a guide to evolutionary relationships

· Closely related living species have DNA base sequences that are more similar than distantly related species.

· The comparative study of base sequences has confirmed many of the more traditional classifications of organisms based on body structure and biochemical similarities.

· For example, based on anatomical evidence, our closest living relatives are chimpanzees. DNA comparisons confirm this: We share more than 98% of our DNA base sequences with chimpanzees.

· One surprising discovery that has been made using this technique is that starlings (Sturnus sp.) are closely related to mockingbirds (Mimus sp.).

Nucleotides have other important roles in the cell

· Some RNA monomers have important roles in energy transfer within cells.

· The ribonucleotide ATP acts as an energy transducer in many biochemical reactions. It is the cash form of cellular energy. (See Chapter 6.)

· The ribonucleotide GTP powers protein synthesis. (See Chapters 12 and 15.)

· cAMP (cyclic AMP) is a special ribonucleotide that is essential for hormone action and the transfer of information by the nervous system.

Lipids: Water-Insoluble Molecules.

· Life is cellular; the differences between what is outside and inside a cell define life.

· Biological molecules called lipids maintain these differences.

· Lipids are diverse biological molecules that share a common chemical property: They are insoluble in water.

· This insolubility results from the many nonpolar covalent bonds of hydrogen and carbon in lipids.

· Lipids aggregate away from water, which is polar, and attract to each other via weak, but additive, van der Waals forces.

· Lipids are technically not polymers, because the subunits are not held together by covalent bonds, but they may be considered so as groupings of individual lipid units.

· The roles for lipids in organisms include energy storage (fats and oils), cell membranes (phospholipids), capture of light energy (carotinoids), hormones and vitamins (steroids and modified fatty acids), thermal insulation, electrical insulation of nerves, and water repellency (waxes and oils).

Fats and oils store energy

· Fats and oils are triglycerides, or simple lipids composed of three fatty acid molecules and one glycerol molecule. (See Figure 3.19.)

· Glycerol (or glycerin) is a three-carbon molecule with three hydroxyl (—OH) groups, one for each carbon.

· Each —OH is the site where an enzyme adds a fatty acid.

· Fatty acids are long linear chains of hydrocarbons with a carboxyl group (—COOH) at one end. (See Figure 3.19.)

· In saturated fatty acids, the hydrocarbon chain has only single carbon-to-carbon bonds. Hydrogen atoms complete the valence requirements, thus saturating the chain.

· Saturated fatty acids are rigid and straight, and they are solid or semisolid at room temperature. (See Figure 3.20a.)

· Animal fats are saturated.

· Unsaturated fatty acids are those that have at least one double-bonded carbon in one of the hydrocarbon chains. At these positions, there are two fewer hydrogen atoms—the chain is not completely saturated with hydrogen atoms.

· The double bonds in unsaturated fatty acids cause rigid kinks that prevent easy packing. As a result, unsaturated fatty acids are liquid at room temperature. (See Figure 3.20b.)

· Plants commonly have short and/or unsaturated fatty acids that tend to be more fluid than animal fats, even at cold temperatures.

· Fats and oils are marvelous storehouses for energy, used by animals and plants for fuel compounds in metabolism.

Phospholipids form the core of biological membranes

· Lipids do not normally interact with water or with the many biologically important substances that are soluble in water.

· Thus lipids play a crucial role in living cells: separating regions with different concentrations of ions and other chemicals.

· Phospholipids have two hydrophobic (“water-hating”) fatty acid tails and one hydrophilic (“water-loving”) phosphate attached to the glycerol. (See Figure 3.21.)

· As a result of this structure, phospholipids orient themselves so that the phosphate group faces water and the tail faces away.

· In aqueous environments, these lipids form bilayers, heads facing outward, tails facing inward. (See Figure 3.22.)

· Cell membranes are structured this way.

Carotenoids and steroids

· Carotenoids and steroids are specialized lipids with chemical structures that are very different from those of triglycerides and phospholipids.

· Carotenoids trap light energy.

· Carotenoids are light-absorbing pigments found in plants and animals.

· One, b-carotene, is a plant pigment used to trap light in photosynthesis. In animals, this pigment—when broken into two identical pieces of vitamin A—is required for vision.

· Steroids are signaling molecules.

· Steroids are organic compounds with a series of fused rings. (See Figure 3.24.)

· Cholesterol is an example. It is a common part of animal cell membranes.

· Cholesterol is absorbed from food and synthesized in the liver.

· In addition to being a membrane constituent, it also is an initial substrate for synthesis of the hormones testosterone and estrogen.

Some lipids are vitamins

· Vitamins are small organic molecules essential to health.

· Vitamin A, for example, is made from b-carotene. It is important for normal development, maintenance of cells, and night vision. (See Figure 3.23.)

· Vitamin D is important for absorption of calcium in the intestines.

· Vitamin E is an antioxidant. It protects membranes.

· Vitamin K is a component required for normal blood clotting.

Wax coatings repel water

· Waxes are highly nonpolar molecules. They protect our hair, birds’ feathers, and insects' eggs from both the damaging effects of excess water, and the damaging effects of water loss.

· Waxes are saturated long fatty acids bonded to long fatty alcohols via an ester linkage.

· A fatty alcohol is similar to a fatty acid except the last carbon has a hydroxyl group (—OH) instead of a carboxyl group (—COOH).

The Interactions of Macromolecules

· In living cells certain macromolecules may be covalently bonded to one another.

· Glycoproteins have polysaccharides covalently bonded to a protein.

· Glycolipids, which often reside on the cell surface membrane, have polysaccharide-bonded lipids.

· Proteins (enzymes) construct and break down biological macromolecules.

· Lipoproteins may serve as carrier proteins, helping to move very hydrophobic lipids through aqueous environments.

· Some proteins are capable of recognizing and affecting other macromolecules, such as proteins, carbohydrates, lipids, and DNA.