BSC 1010C
General Biology I
Dr. Graeme Lindbeck
glindbeck@valenciacollege.edu

The Structure and Function of Macromolecules

Outline

1. Most macromolecules are polymers
2. A limitless variety of polymers can be built from a small set of monomers
3. Organisms use carbohydrates for fuel and building material
   1. Monosaccharides
   2. Disaccharides
   3. Polysaccharides
4. Lipids are mostly hydrophobic molecules with diverse functions
   1. Fats
   2. Phospholipids
   3. Steroids
5. Proteins are the molecular tools for most cellular functions
6. A polypeptide is a polymer of amino acids connected in a specific sequence
7. A protein's function depends on its specific conformation
   1. Four Levels of Protein Structure
   2. What Determines Protein Conformation?
   3. The Protein-Folding Problem
8. Nucleic acids store and transmit hereditary information
9. A DNA strand is a polymer with an information-rich sequence of nucleotides
10. Inheritance is based on precise replication of DNA

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I. 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.

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.

• One monomer loses a hydroxyl (-OH), and the other monomer loses a hydrogen (-H).
• Removal of water is actually indirect, involving the formation of "activated" monomers
• Process requires energy.
• 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.

• A hydrogen from the water bonds to one monomer, and the hydroxyl bonds to the adjacent monomer.
• For example: digestive enzymes catalyze hydrolytic reactions which break apart large food molecules into monomers that can be absorbed into the bloodstream.

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II. A limitless 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.

• There is unity in life as there are only about 40 - 50 common monomers used to construct macromolecules.
• There is diversity in life as new properties emerge when these universal monomers are arranged in different ways.

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III. Organisms use carbohydrates for fuel and building material

Carbohydrates = Organic molecules made of sugars and their polymers.

• Monomers or building block molecules are simple sugars called monosaccharides.
• Polymers are formed by condensation reactions.
• Are classified based upon the number of simple sugars.

Monosaccharides

Monosaccharides = (Mono = single; sacchar = sugar) Simple sugar in which C, H and O occur in the ratio of (CH₂O).

• Are major nutrients for cells. Glucose is the most common.
• Can be produced (glucose) by photosynthetic organisms from CO₂, H₂O and sunlight.
• Store energy in their chemical bonds which is harvested by cellular respiration.
• Their carbon skeletons are raw material for other organic molecules.
• Can be incorporated as monomers into disaccharides and polysaccharides.

Characteristics of a sugar:

1. An -OH group is attached to each carbon except one, which is double bonded to an oxygen (carbonyl).
2. Size of the carbon skeleton varies from 3 to 7 carbons. The most common monosaccharides are:

   Classification	Number of Carbons	Example
   Triose	3	Glyceraldehyde
   Pentose	5	Ribose
   Hexose	6	Glucose

3. 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.
4. In aqueous solutions, many monosaccharides form rings. Chemical equilibrium favors the ring structure.

Disaccharides

Disaccharides = (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

• Examples of Disaccharides:

  Disaccharide	Monomers	General Comments
  Maltose	Glucose + Glucose	Sugar important in brewing beer.
  Lactose	Glucose + G alactose	Sugar present in milk.
  Sucrose	Glucose + Fructose	Table sugar; most prevalent disaccharide; transport form in plants.

Polysaccharides

Polysaccharides = Macromolecules that are polymers of a few hundred or thousand monosaccharides.
• Are formed by linking monomers in enzyme-mediated condensation reactions.
• 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.

• Helical glucose polymer with (a-1,4 linkages)
• Stored as granules within plant organelles called plastids.
• Amylose, the simplest form, is an unbranched polymer.
• Amylopectin is branched polymer.
• Most animals have digestive enzymes to hydrolyze starch.
• 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.

• Large glucose polymer that is more highly branched than amylopectin.
• 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 b-1,4 linkages.

• A major structural component of plant cell walls.
• Differs from starch (also a glucose polymer) it its glycosidic linkages.

  STARCH	CELLULOSE
  Glucose monomers are in a configuration. -OH group on carbon one is below the ring's plane. Monomers are connected with a-1,4 linkage.	Glucose monomers are in b configuration -OH group on carbon one is above the ring's plane. Monomers are connected with b-1,4 linkage.

• Cellulose and starch have different three-dimensional shapes and properties as a result of differences in glycosidic linkages.
• Cellulose reinforces plant cell walls. Hydrogen bonds hold together parallel cellulose molecules in bundles of microfibrils.
• 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.

• Forms exoskeletons of arthropods.
• Found as a building material in the cell walls of some fungi.
• Monomer is an amino sugar, which is similar to beta-glucose with a nitrogen-containing group
• replacing the hydroxyl on carbon 2.

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IV. Lipids are mostly hydrophobic molecules with diverse functions

Fats

Fats = Macromolecules constructed from:

1. Glycerol, a three-carbon alcohol.
2. Fatty acid (carboxylic acid).
   • Composed of a carboxyl group at one end and an attached hydrocarbon chain ("tail").
   • Carboxyl functional group ("head") has properties of an acid.
   • Hydrocarbon chain has a long, carbon skeleton usually with an even number of carbon atoms (most have 16 - 18 carbons).
   • 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. 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 linkage (triglyceride).

Some characteristics of fat include:

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

  Saturated Fats	Unsaturated Fats
  No double bonds between carbons in fatty acid tail Carbon skeleton of fatty acid is bonded to maximum number of hydrogens (saturated) Usually solid at room temperature Most animal fats e.g., bacon grease, lard and butter	One or more double bonds carbons in fatty acid tail Tail kinks at each C=C, so molecules do not pack closely enough to solidify at room temperature Usually a liquid at room temperature Most plant fats e.g., corn, peanut and olive

• 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, such as:

• 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.)
• More compact fuel reservoir than carbohydrate. Animals store more energy with less weight than plants which use starch, a bulky form of energy storage.
• Cushions vital organs in mammals (e.g. kidney).
• Insulates against heat loss (e.g. mammals such as whales and seals).

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.

• Differ from fat in that the third carbon of glycerol is joined to a negatively charged phosphate group.
• Can have small variable molecules (usually charged or polar) attached to phosphate head
• Are diverse depending upon differences in fatty acids and in phosphate attachments.
• Show ambivalent behavior towards water. Hydrocarbon tails are hydrophobic, and the polar head (phosphate group with attachments) is hydrophilic.
• Cluster in water as their hydrophobic portions turn away from water. One such cluster, a micelle, assembles so the hydrophobic tails turn towards the water-free interior; and the hydrophilic phosphate heads arrange facing outward in contact with water.
• 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.

Steroids

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

Cholesterol, 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.

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V. Proteins are the molecular tools for most cellular functions

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.

• Are abundant, making up 50% or more of cellular dry weight.
• 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).
• Vary extensively in structure; each type has a unique three-dimensional shape (conformation).
• Though vary in structure and function, are commonly made of only 20 amino acid monomers.

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VI. A polypeptide is a polymer of amino acids connected in a specific sequence

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. (At pH's normally found in cells, both the carbonyl and amino groups are ionized.)

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 predominate s.

The twenty common amino acids can be grouped by properties of side chains:

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:
   1. Uncharged polar.
   2. 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.

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 -N-C-C-N-C-C-.

Polypeptide chains:

• Range in length from a few monomers to more than a thousand.
• Have unique linear sequences of amino acids.

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VII. A protein's function depends on its specific conformation

Protein conformnation = Three-dimensional shape of a protein.

Native conformation = Functional conformation of a protein found under normal biological conditions.

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

Four Levels of Protein Structure

The correlation between form and function in proteins is an emergent property resulting from superimposed levels of protein structure:

1. Primary structure.
2. Secondary structure.
3. Tertiary structure.

When a protein has two or more polypeptide chains, it also has:


4. Quaternary structure.

1. Primary Structure

Primary structure = Unique sequence of amino acids in a protein.

• Determined by genes,
• Slight change can affect a protein's conformation and function (e.g. sickle-cell hemoglobin)
• Can be sequenced in the laboratory. A pioneer in this work was Frederick Sanger who determined the amino acid sequence in insulin (late 1940's and early 1950's). 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.
• Most of the sequencing process is now automated.

2. Secondary Structure

Secondary structure = Regular, repeated coiling and folding of a protein's polypeptide backbone.

• Contributes to a protein's overall conformation.
• Stabilized by hydrogen bonds between peptide linkages in the protein's backbone (carbonyl and amino groups).
• The major types of secondary structure are alpha (a) helix and beta (b) pleated sheet.
  1. Alpha (a) Helix

     Alpha (a) 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).

     • Described by Linus Pauling and Robert Corey in 1951.
     • 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 (b) pleated sheet = Secondary protein structure which is a sheet of antiparallel chains folded into accordion pleats.

     • Parallel regions are held together by either intrachain or interchain hydrogen bonds (between adjacent polypeptides).
     • 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).

3. Tertiary Structure

Tertiary structure = Irregular contortions of a protein due to bonding between side chains (R groups); third level of protein structure superimposed upon primary and secondary structure.

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:

   • Hydrogen bonding between polar side chains.
   • Ionic bonds between charged side chains.
   • 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. (S of one cysteine sulfhydryl, bonds to the S of a second cysteine.)

4. Quaternary Structure

Quaternary structure = Structure that results from the interaction among several polypeptides (subunits) in a single protein.

• For 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.
• Some globular proteins have subunits that fit tightly together. For example: hemoglobin, a globular protein that has four subunits (two a chains and two b chains).

What Determines Protein Conformation?

A protein's three-dimensional shape is a consequence of the interactions responsible for secondary and tertiary structure.

• This conformation is influenced by physical and chemical environmental conditions.
• 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:

• 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.
• Chemical agents that disrupt hydrogen bonds, ionic bonds and disulfide bridges.
• Excessive heat. Increased thermal agitation disrupts weak interactions.

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.

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:

• 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.
• 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
• Biochemists can now track a protein as it passes through its intermediate stages during the folding process.
• 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.

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VIII. 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)
   • Contains coded information that programs all cell activity.
   • Contains directions for its own replication.
   • Is copied and passed from one generation of cells to another.
   • In eukaryotic cells, is found primarily in the nucleus.
   • 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)
   • Functions in the actual synthesis of proteins coded for by DNA.
   • Sites of protein synthesis are on ribosomes in the cytoplasm.
   • Messenger RNA (mRNA) carries encoded genetic message from the nucleus to the cytoplasm.

The flow of genetic information goes from DNA ® RNA ® protein.

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IX. A DNA strand is a polymer with an information-rich sequence 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. Ribose is the pentose in RNA. Deoxyribose is the pentose in DNA. (It lacks the -OH group at number two carbon.)

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:

   • Cytosine (C)
   • Thymine (T) - found only in DNA
   • Uracil (U) - found only in RNA.
   Purine = Nitrogenous base characterized by a five-membered ring fused to a six-membered ring. For example:
   • Adenine (A)
   • Guanine (G)

Nucleotides have various functions:

• Are monomers for nucleic acids.
• Transfer chemical energy from one molecule to another (e.g. ATP).
• Are electron acceptors in enzyme-controlled redox reactions of the cell (e.g. NAD).

DNA is a polymer of nucleotides joined by phosphodiester linkages between the phosphate of one nucleotide and the sugar of the next.

• Results in a backbone with a repeating pattern of sugar-phosphate-sugar-phosphate.
• Variable nitrogenous bases are attached to the sugar-phosphate backbone.
• Each gene contains a unique linear sequence of nitrogenous bases which codes for a unique linear sequence of amino acids in a protein.

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X. Inheritance is based on precise replication of DNA

In 1953, James Watson and Francis Crick proposed the double helix as the three dimensional structure of DNA.

• Consists of two nucleotide chains wound in a double helix.
• Sugar-phosphate backbones are on the outside of the helix.
• Nitrogenous bases are paired in the interior of the helix and are held together by hydrogen bonds.
• Base-pairing rules are that adenine (A) always pairs with thymine (T); guanine (G) always pairs with cytosine (C).
• 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.
• Most DNA molecules are long - with thousands or millions of base pairs.

Course Pages maintained by
Dr. Graeme Lindbeck.