CHAPTER 5 - The Structure and Function of Macromolecules

LECTURE NOTES Chapter 5 - The Structure and Function of Macromolecules

The topic of macromolecules lends itself well to illustrate three integral themes that permeate the text and course:
1. There is a natural hierarchy of structural level in biological organization.
2. As one moves up the hierarchy, new properties emerge because of interactions among subunits at the lower levels.
3. Form fits function.

I. Polymer Principles
A. Most macromolecules are polymers
Polymer = (Poly = many; mer = part); large molecule consisting of many identical or similar subunits connected together.
Monomer = Subunit or building block molecule of a polymer
Macromolecule = (Macro = large); large organic polymer
· Formation of macromolecules from smaller building block molecules represents another level in the hierarchy of biological organization.
· There are four classes of macromolecules in living organisms:
1. Carbohydrates
2. Lipids
3. Proteins
4. Nucleic acids

Most polymerization reactions in living organisms are condensation reactions.
o Polymerization reactions = Chemical reactions that link two or more small molecules to form larger molecules with repeating structural units.

Condensation reactions = Polymerization reactions during which monomers are covalently linked, producing net removal of a water molecule for each covalent linkage.
o One monomer loses a hydroxyl (–OH), and the other monomer loses a hydrogen (–H).
o Removal of water is actually indirect, involving the formation of "activated" monomers
o Process requires energy.
o Process requires biological catalysts or enzymes.

Hydrolysis = (Hydro = water; lysis = break); a reaction process that breaks covalent bonds between monomers by the addition of water molecules.
o A hydrogen from the water bonds to one monomer, and the hydroxyl bonds to the adjacent monomer.
o Example: Digestive enzymes catalyze hydrolytic reactions which break apart large food molecules into monomers that can be absorbed into the bloodstream.

B. An immense variety of polymers can be built from a small set of monomers Structural variation of macromolecules is the basis for the enormous diversity of life.
o There is unity in life as there are only about 40 to 50 common monomers used to construct macromolecules.
o There is diversity in life as new properties emerge when these universal monomers are arranged in different ways.

II. Carbohydrates: Fuel and Building Material
A. Sugars, the smallest carbohydrates, serve as fuel and carbon sources
Carbohydrates = Organic molecules made of sugars and their polymers
o Monomers or building block molecules are simple sugars called monosaccharides.
o Polymers are formed by condensation reactions.
o Carbohydrates are classified by the number of simple sugars.

1. Monosaccharides
Monosaccharides = (Mono = single; sacchar = sugar); simple sugar in which C, H, and O occur in the ratio of (CH2O).
o Are major nutrients for cells; glucose is the most common
o Can be produced (glucose) by photosynthetic organisms from CO2, H2O, and sunlight
o Store energy in their chemical bonds which is harvested by cellular respiration
o Their carbon skeletons are raw material for other organic molecules.
o Can be incorporated as monomers into disaccharides and polysaccharides

Characteristics of a sugar:
a. An –OH group is attached to each carbon except one, which is double bonded to an oxygen (carbonyl).




b. Size of the carbon skeleton varies from three to seven carbons. The most common monosaccharides are:


c. Spatial arrangement around asymmetric carbons may vary. For example, glucose and galactose are enantiomers.

The small difference between isomers affects molecular shape which gives these molecules distinctive biochemical properties.

d. In aqueous solutions, many monosaccharides form rings. Chemical equilibrium favors the ring structure.

2. Disaccharides
Disaccharide = (Di = two; sacchar = sugar); a double sugar that consists of two monosaccharides joined by a glycosidic linkage.
Glycosidic linkage = Covalent bond formed by a condensation reaction between two sugar monomers; for example, maltose:

Examples of disaccharides include:

B. Polysaccharides, the polymers of sugars, have storage and structural roles
Polysaccharides = Macromolecules that are polymers of a few hundred or thousand monosaccharides.
o Are formed by linking monomers in enzyme-mediated condensation reactions
o Have two important biological functions:
1. Energy storage (starch and glycogen)
2. Structural support (cellulose and chitin)

1. Storage polysaccharides
Cells hydrolyze storage polysaccharides into sugars as needed. Two most common storage polysaccharides are starch and glycogen.

Starch = Glucose polymer that is a storage polysaccharide in plants.
o Helical glucose polymer with a 1-4 linkages (see Campbell, Figure 5.6)
o Stored as granules within plant organelles called plastids
o Amylose, the simplest form, is an unbranched polymer.
o Amylopectin is branched polymer.
o Most animals have digestive enzymes to hydrolyze starch.
o Major sources in the human diet are potato tubers and grains (e.g., wheat, corn, rice, and fruits of other grasses).

Glycogen = Glucose polymer that is a storage polysaccharide in animals.
o Large glucose polymer that is more highly branched (a 1-4 and 4-6
linkages) than amylopectin
o Stored in the muscle and liver of humans and other vertebrates

2. Structural polysaccharides
Structural polysaccharides include cellulose and chitin.
Cellulose = Linear unbranched polymer of D-glucose in (a 1-4, b 4-6) linkages.
o A major structural component of plant cell walls
o Differs from starch (also a glucose polymer) in its glycosidic linkages (see


o Cellulose and starch have different three-dimensional shapes and properties as a result of differences in glycosidic linkages.
o Cellulose reinforces plant cell walls. Hydrogen bonds hold together parallel cellulose molecules in bundles of microfibrils (see Campbell, Figure 5.8)
o Cellulose cannot be digested by most organisms, including humans, because they lack an enzyme that can hydrolyze the b 1-4 linkage. (Exceptions are some symbiotic bacteria, other microorganisms and some fungi.)

Chitin = A structural polysaccharide that is a polymer of an amino sugar (see Campbell, Figure 5.9).
o Forms exoskeletons of arthropods
o Found as a building material in the cell walls of some fungi
o Monomer is an amino sugar, which is similar t o beta-glucose with a nitrogen-containing group replacing the hydroxyl on carbon 2.

III. Lipids: Diverse Hydrophobic Molecules
Lipids = Diverse group of organic compounds that are insoluble in water, but will dissolve in nonpolar solvents (e.g., ether, chloroform, benzene). Important groups are fats, phospholipids, and steroids.

A. Fats store large amounts of energy
Fats = Macromolecules are constructed from (see Campbell, Figure 5.10):
1. Glycerol, a three-carbon alcohol
2. Fatty acid (carboxylic acid)
o Composed of a carboxyl group at one end and an attached hydrocarbon chain ("tail")
o Carboxyl functional group ("head") has properties of an acid.
o Hydrocarbon chain has a long carbon skeleton usually with an even number of carbon atoms (most have 16 – 18 carbons).
o Nonpolar C–H bonds make the chain hydrophobic and not water soluble.

During the formation of a fat, enzyme- catalyzed condensation reactions link glycerol to fatty acids by an ester linkage.
Ester linkage = Bond formed between a hydroxyl group and a carboxyl group. H-C-OH

Glycerol
Each of glycerol’s three hydroxyl groups can bond to a fatty acid by an ester linkage producing a fat.
Triacylglycerol = A fat composed of three fatty acids bonded to one glycerol by ester linkages (triglyceride).

Some characteristics of fat include:
o Fats are insoluble in water. The long fatty acid chains are hydrophobic because of the many nonpolar C–H bonds.
o The source of variation among fat molecules is the fatty acid composition.
o Fatty acids in a fat may all be the same, or some (or all) may differ.
o Fatty acids may vary in length.
o Fatty acids may vary in the number and location of carbon-to-carbon double bonds.

o In many commercially prepared food products, unsaturated fats are artificially hydrogenated to prevent them from separating out as oil (e.g., peanut butter and margarine).

Fat serves many useful functions:
o Energy storage. One gram of fat stores twice as much energy as a gram of polysaccharide. (Fat has a higher proportion of energy rich C–H bonds.)
o More compact fuel reservoir than carbohydrate. Animals store more energy with less weight than plants which use starch, a bulky form of energy storage.
o Cushions vital organs in mammals (e.g., kidney).
o Insulates against heat loss (e.g., in mammals such as whales and seals).

B. Phospholipids
Phospholipids = Compounds with molecular building blocks of glycerol, two fatty acids, a phosphate group, and usually, an additional small chemical group attached to the phosphate (see Campbell , Figure 5.12)
o Differ from fat in that the third carbon of glycerol is joined to a negatively charged phosphate group
o Can have small variable molecules (usually charged or polar) attached t o phosphate
o Are diverse depending upon differences in fatty acids and in phosphate attachments
o Show ambivalent behavior toward water. Hydrocarbon tails are hydrophobic and the polar head (phosphate group with attachments) is hydrophilic.
o Cluster in water as their hydrophobic portions turn away from water. One such cluster, a micelle, assembles so the hydrophobic tails turn toward the water-free interior and the hydrophilic phosphate heads arrange facing outward in contact with water (see Campbell, Figure 5.13).
o Are major constituents of cell membranes. At the cell surface, phospholipids form a bilayer held together by hydrophobic interactions among the
hydrocarbon tails. Phospholipids in water will spontaneously form such a bilayer.

C. Steroids
Steroids = Lipids which have four fused carbon rings with various functional groups attached.

Cholesterol is an important steroid.
· Is the precursor to many other steroids including vertebrate sex hormones and bile acids.
· Is a common component of animal cell membranes.
· Can contribute to atherosclerosis.

IV. Proteins: The Molecular Tools of the Cell
Polypeptide chains = Polymers of amino acids that are arranged in a specific linear sequence and are linked by peptide bonds.
Protein = A macromolecule that consists of one or more polypeptide chains folded and coiled into specific conformations.
o Are abundant, making up 50% or more of cellular dry weight

o Have important and varied functions in the cell:
1. Structural support
2. Storage (of amino acids)
3. Transport (e.g., hemoglobin)
4. Signaling (chemical messengers)
5. Cellular response to chemical stimuli (receptor proteins)
6. Movement (contractile proteins)
7. Defense against foreign substances and disease-causing organisms (antibodies)
8. Catalysis of biochemical reactions (enzymes)

o Vary extensively in structure; each type has a unique three-dimensional shape (conformation)
o Though they vary in structure and function, they are commonly made of only 20 amino acid monomers.

A. A polypeptide is a polymer of amino acids connected in a specific sequence
Amino acid = Building block molecule of a protein; most consist of an asymmetric carbon, termed the alpha carbon, which is covalently bonded to a(n):
1. Hydrogen atom.
2. Carboxyl group.
3. Amino group.
4. Variable R group (side chain) specific to each amino acid. Physical and chemical properties of the side chain determine the uniqueness of each amino acid.

Amino acids contain both carboxyl and amino functional groups. Since one group acts as a weak acid and the other group acts as a weak base, an amino acid can exist in three ionic states. The pH of the solution determines which ionic state predominates.

The twenty common amino acids can be grouped by properties of side chains (see Campbell, Figure 5.15):
1. Nonpolar side groups (hydrophobic). Amino acids with nonpolar groups are less soluble in water.
2. Polar side groups (hydrophilic). Amino acids with polar side groups are soluble in water. Polar amino acids can be grouped further into:
a. Uncharged polar
b. Charged polar
3. Acidic side groups. Dissociated carboxyl group gives these side groups a negative charge.
4. Basic side groups. An amino group with an extra proton gives these side groups a net positive charge.

Polypeptide chains are polymers that are formed when amino acid monomers are linked by peptide bonds (see Campbell, Figure 5.16).


Peptide bond = Covalent bond formed by a condensation reaction that links the carboxyl group of one amino acid to the amino group of another.

· Has polarity with an amino group on one end (N-terminus) and a carboxyl group on the other (C-terminus).

· Has a backbone of the repeating sequence

Polypeptide chains:
o Range in length from a few monomers to more than a thousand.
o Have unique linear sequences of amino acids.

B. A protein’s function depends on its specific conformation A protein’s function depends upon its unique conformation. Protein conformation = Three-dimensional shape of a protein.
Native conformation = Functional conformation of a protein found under normal biological conditions.

o Enables a protein to recognize and bind specifically to another molecule (e.g., hormone/receptor, enzyme/substrate, and antibody/antigen)
o Is a consequence of the specific linear sequence of amino acids in the polypeptide
o Is produced when a newly formed polypeptide chain coils and folds spontaneously, mostly in response to hydrophobic interactions
o Is stabilized by chemical bonds and weak interactions between neighboring regions of the folded protein

1. Four levels of protein structure
The correlation between form and function in proteins is an emergent property resulting from superimposed levels of protein structure (see Campbell, Figure 5.24):

o Primary structure
o Secondary structure
o Tertiary structure
o When a protein has two or more polypeptide chains, it also has quaternary structure.

a. Primary structure
Primary structure = Unique sequence of amino acids in a protein.
o Determined by genes
o Slight change can affect a protein’s conformation and function (e.g., sickle-cell hemoglobin; see Campbell, Figure 5.19).
o Can be sequenced in the laboratory. A pioneer in this work was Frederick Sanger who determined the amino acid sequence in insulin
(late 1940s and early 1950s). This laborious process involved:
1) Determination of amino acid composition by complete acid hydrolysis of peptide bonds and separation of resulting amino acids by chromatography. Using these techniques, Sanger identified the amino acids and determined the relative proportions of each.
2) Determination of amino acid sequence by partial hydrolysis with enzymes and other catalysts to break only specific peptide bonds. Sanger deductively reconstructed the primary structure from fragments with overlapping segments.
o Most of the sequencing process is now automated.

b. Secondary structure
Secondary structure = Regular, repeated coiling and folding of a protein’s polypeptide backbone (see Campbell, Figure 5.20).
o Contributes to a protein’s overall conformation.
o Stabilized by hydrogen bonds between peptide linkages in the protein’s backbone (carbonyl and amino groups).
o The major types of secondary structure are alpha (a) helix and beta (b) pleated sheet.

1) Alpha (a) helix
Alpha ( ) helix = Secondary structure of a polypeptide that is a helical coil stabilized by hydrogen bonding between every fourth peptide bond
(3.6 amino acids per turn).
o Described by Linus Pauling and Robert Corey in 1951.
o Found in fibrous proteins (e.g., a-keratin and collagen) for most of their length and in some portions of globular proteins.

2) Beta (b) pleated sheet
Beta ( ) pleated sheet = Secondary protein structure which is a sheet of antiparallel chains folded into accordion pleats.
o Parallel regions are held together by either intrachain or interchain hydrogen bonds (between adjacent polypeptides).
o Make up the dense core of many globular proteins (e.g., lysozyme) and the major portion of some fibrous proteins (e.g., fibroin, the structural protein of silk).

c. Tertiary structure
Tertiary structure = The three-dimensional shape of a protein. The irregular contortions of a protein are due to bonding between and among side chains (R groups) and to interaction between R groups and the aqueous environment (see Campbell, Figure 5.22).
Types of bonds contributing to tertiary structure are weak interactions and covalent linkage (both may occur in the same protein).

1) Weak interactions
Protein shape is stabilized by the cumulative effect of weak interactions. These weak interactions include:
o Hydrogen bonding between polar side chains.
o Ionic bonds between charged side chains.
o Hydrophobic interactions between nonpolar side chains in protein’s interior.
Hydrophobic interactions = (Hydro = water; phobos = fear); the clustering of hydrophobic molecules as a result of their mutual exclusion from water.

2) Covalent linkage
Disulfide bridges form between two cysteine monomers brought together by folding of the protein. This is a strong bond that reinforces conformation.

d. Quaternary structure
Quaternary structure = Structure that results from the interactions between and among several polypeptides chains (subunits) (see Campbell, Figure 5.23).
o Example: Collagen, a fibrous protein with three helical polypeptides supercoiled into a triple helix; found in animal connective tissue, collagen’s supercoiled quaternary structure gives it strength.
o Some globular proteins have subunits that fit tightly together. Example: Hemoglobin, a globular protein that has four subunits (two a chains and
two b chains)

2. What determines protein conformation?

A protein’s three-dimensional shape is a consequence of the interactions responsible for secondary and tertiary structure.
o This conformation is influenced by physical and chemical environmental conditions.
o If a protein’s environment is altered, it may become denatured and lose its native conformation.
Denaturation = A process that alters a protein’s native conformation and biological activity. Proteins can be denatured by:

o Transfer to an organic solvent. Hydrophobic side chains, normally inside the protein’s core, move towards the outside. Hydrophilic side chains turn
away from the solvent towards the molecule’s interior.
o Chemical agents that disrupt hydrogen bonds, ionic bonds and disulfide bridges.
o Excessive heat. Increased thermal agitation disrupts weak interactions (see Campbell, Figure 5.25).

The fact that some denatured proteins return to their native conformation when environmental conditions return to normal is evidence that a protein’s amino acid sequence (primary structure) determines conformation. It influences where and which interactions will occur as the molecule arranges into secondary and tertiary structure.

3. The protein-folding problem

Even though primary structure ultimately determines a protein’s conformation, three-dimensional shape is difficult to predict solely on the basis of amino acid sequence. It is difficult to find the rules of protein folding because:
o Most proteins pass through several intermediate stages in the folding process; knowledge of the final conformation does not reveal the folding
process required to create it.
o A protein’s native conformation may be dynamic, alternating between several shapes. Using recently developed techniques, researchers hope to gain new insights into protein folding:
o Biochemists can now track a protein as it passes through its intermediate stages during the folding process.
o Chaperone proteins have just been discovered that temporarily brace a folding protein.

Rules of protein folding are important to molecular biologists and the biotechnology industry. This knowledge should allow the design of proteins for specific purposes.

V. Nucleic Acids: Informational Polymers

A. Nucleic acids store and transmit hereditary information
Protein conformation is determined by primary structure. Primary structure, in turn, is determined by genes; hereditary units that consist of DNA, a type of nucleic acid.

There are two types of nucleic acids.

1. Deoxyribonucleic acid (DNA)
o Contains coded information that programs all cell activity.
o Contains directions for its own replication.
o Is copied and passed from one generation of cells to another.
o In eukaryotic cells, is found primarily in the nucleus.
o Makes up genes that contain instructions for protein synthesis. Genes do not directly make proteins, but direct the synthesis of mRNA.

2. Ribonucleic acid (RNA)
o Functions in the actual synthesis of proteins coded for by DNA.
o Sites of protein synthesis are on ribosomes in the cytoplasm.
o Messenger RNA (mRNA) carries encoded genetic message from the nucleus to the cytoplasm.
o The flow of genetic information goes from DNA ® RNA ® protein (see Campbell, Figure 5.26).

 

B. A nucleic acid strand is a polymer of nucleotides
Nucleic acid = Polymer of nucleotides linked together by condensation reactions.
Nucleotide = Building block molecule of a nucleic acid; made of (1) a five-carbon sugar
covalently bonded to (2) a phosphate group and (3) a nitrogenous base.
1. Pentose (5-carbon sugar)
There are two pentoses found in nucleic acids: ribose and deoxyribose.

2. Phosphate
The phosphate group is attached to the number 5 carbon of the sugar.

3. Nitrogenous base
There are two families of nitrogenous bases:

Pyrimidine = Nitrogenous base characterized by a six-membered ring made up of carbon and nitrogen atoms. For example:
o Cytosine (C)
o Thymine (T); found only in DNA
o Uracil (U); found only in RNA

Purine = Nitrogenous base characterized by a five-membered ring fused to a sixmembered ring. For example:
o Adenine (A)
o Guanine (G)

Nucleotides have various functions:
o Are monomers for nucleic acids.
o Transfer chemical energy from one molecule to another (e.g., ATP).
o Are electron acceptors in enzyme-controlled redox reactions of the cell (e.g., NAD).

A nucleic-acid polymer or polynucleotise, results from joining nucleotides together by covalent bonds called phosphodiester linkages. The bond is formed between the phosphate of one nucleotide and the sugar of the next.
o Results in a backbone with a repeating pattern of sugar-phosphate-sugar-phosphate.
o Variable nitrogenous bases are attached to the sugar-phosphate backbone.
o Each gene contains a unique linear sequence of nitrogenous bases which codes for a unique linear sequence of amino acids in a protein.

C. Inheritance is based on precise replication of the DNA double helix
In 1953, James Watson and Francis Crick proposed the double helix as the three dimensional structure of DNA.
o Consists of two nucleotide chains wound in a double helix.
o Sugar-phosphate backbones are on the outside of the helix.
o The two polynucleotide strands of DNA are held together by hydrogen bonds between the paired nitrogenous bases and by van der Waals attraction between the stacked bases (see Campbell, Figure 5.28).
o Base-pairing rules are that adenine (A) always pairs with thymine (T); guanine G) always pairs with cytosine (C).
o Two strands of DNA are complimentary and thus can serve as templates to make new complementary strands. It is this mechanism of precise copying that makes inheritance possible.
o Most DNA molecules are long, containing thousands or millions of base pairs.

D. We can use DNA and proteins as tape measures of evolution
Closely related species have more similar sequences of DNA and amino acids, than more distantly related species. Using this type of molecular evidence, biologists can deduce evolutionary relationships among species.