H-B Woodlawn Biology - Jim’s Discussion Notes

 

THE STRUCTURE AND FUNCTION OF MACROMOLECULES

 

Introduction

·      Cells join smaller organic molecules together to form larger molecules.

·      These larger molecules, macromolecules, may be composed of thousands of atoms and weigh over 100,000 daltons.

·      The four major classes of macromolecules are: carbohydrates, lipids, proteins, and nucleic acids.

 

A. Polymer principles

1. Most macromolecules are polymers

·      Three of the four classes of macromolecules form chainlike molecules called polymers.

·      Polymers consist of many similar or identical building blocks linked by covalent bonds.

·      The repeated units are small molecules called monomers.

·      Some monomers have other functions of their own.

·      The chemical mechanisms that cells use to make and break polymers are similar for all classes of macromolecules.

·      Monomers are connected by covalent bonds via a condensation reaction or dehydration reaction.

·      One monomer provides a hydroxyl group and the other provides a hydrogen and together these form water.

·      This process requires energy and is aided by enzymes.

·      The covalent bonds connecting monomers in a polymer are disassembled by hydrolysis.

·      In hydrolysis, as the covalent bond is broken a hydrogen atom and hydroxyl group from a split water molecule attaches where the covalent bond used to be.

·      Hydrolysis reactions dominate the digestive process, guided by specific enzymes.

 

2. An immense variety of polymers can be built from a small set of monomers

·      Each cell has thousands of different macromolecules.

·      These molecules vary among cells of the same individual; they vary more among unrelated individuals of a species, and even more between species.

·      This diversity comes from various combinations of the 40-50 common monomers and other rarer ones.

·      These monomers can be connected in various combinations, like the 26 letters in the alphabet can be used to create a great diversity of words.

·      Biological molecules are even more diverse.

 

B. Carbohydrates - Fuel and Building Material

·      Carbohydrates include both sugars and polymers.

·      The simplest carbohydrates are monosaccharides or simple sugars.

·      Disaccharides, double sugars, consist of two monosaccharides joined by a condensation reaction.

·      Polysaccharides are polymers of monosaccharides.

 

1. Sugars, the smallest carbohydrates serve as a source of fuel and carbon sources

·      Monosaccharides generally have molecular formulas that are some multiple of CH2O.

·      For example, glucose has the formula C6H12O6.

·      Most names for sugars end in -ose.

·      Monosaccharides have a carbonyl group and multiple hydroxyl groups.

·      If the carbonyl group is at the end, the sugar is an aldose, if not, the sugars is a ketose.

·      Glucose, an aldose, and fructose, a ketose, are structural isomers.

·      Monosaccharides are also classified by the number of carbons in the backbone.

·      Glucose and other six carbon sugars are hexoses.

·      Five carbon backbones are pentoses and three carbon sugars are trioses.

·      Monosaccharides may also exist as enantiomers.

·      For example, glucose and galactose, both six-carbon aldoses, differ in the spatial arrangement around asymmetrical carbons.

·      Monosaccharides, particularly glucose, are a major fuel for cellular work.

·      They also function as the raw material for the synthesis of other monomers, including those of amino acids and fatty acids.

·      Two monosaccharides can join with a glycosidic linkage to form a dissaccharide via dehydration.

·      Maltose, malt sugar, is formed by joining two glucose molecules.

·      Sucrose, table sugar, is formed by joining glucose and fructose and is the major transport form of sugars in plants.

·      While often drawn as a linear skeleton, in aqueous solutions monosaccharides form rings.

 

2. Polysaccharides, the polymers of sugars, have storage and structural roles

·      Polysaccharides are polymers of hundreds to thousands of monosaccharides joined by glycosidic linkages.

·      One function of polysaccharides is as an energy storage macromolecule that is hydrolyzed as needed.

·      Other polysaccharides serve as building materials for the cell or whole organism.

·      Starch is a storage polysaccharide composed entirely of glucose monomers.

·      Most monomers are joined by 1-4 linkages between the glucose molecules.

·      One unbranched form of starch, amylose, forms a helix.

·      Branched forms, like amylopectin, are more complex.

·      Plants store starch within plastids, including chloroplasts.

·      Plants can store surplus glucose in starch and withdraw it when needed for energy or carbon.

·      Animals that feed on plants, especially parts rich in starch, can also access this starch to support their own metabolism.

·      Animals also store glucose in a polysaccharide called glycogen.

·      Glycogen is highly branched, like amylopectin.

·      Humans and other vertebrates store glycogen in the liver and muscles but only have about a one day supply.

·      While polysaccharides can be built from a variety of monosaccharides, glucose is the primary monomer used in polysaccharides.

·      One key difference among polysaccharides develops from 2 possible ring structures of glucose.

·      These two ring forms differ in whether the hydroxyl group attached to the number 1 carbon is fixed above (beta glucose) or below (alpha glucose) the ring plane.

·      Starch is a polysaccharide of alpha glucose monomers.

·      Structural polysaccharides form strong building materials.

·      Cellulose is a major component of the tough wall of plant cells.

·      Cellulose is also a polymer of glucose monomers, but using beta rings.

·      While polymers built with alpha glucose form helical structures, polymers built with beta glucose form straight structures.

·      This allows H atoms on one strand to form hydrogen bonds with OH groups on other strands.

·      Groups of polymers form strong strands, microfibrils, which are basic building material for plants (and humans).

·      The enzymes that digest starch cannot hydrolyze the beta linkages in cellulose.

·      Cellulose in our food passes through the digestive tract and is eliminated in feces as “insoluble fiber.”

·      As it travels through the digestive tract, it abrades the intestinal walls and stimulates the secretion of mucus.

·      Some microbes can digest cellulose to its glucose monomers through the use of cellulase enzymes.

·      Many eukaryotic herbivores, like cows and termites, have symbiotic relationships with cellulolytic microbes, allowing them access to this rich source of energy.

·      Another important structural polysaccharide is chitin, used in the exoskeletons of arthropods (including insects, spiders, and crustaceans).

·      Chitin is similar to cellulose, except that it contains a nitrogen-containing appendage on each glucose.

·      Pure chitin is leathery, but the addition of calcium carbonate hardens the chitin.

·      Chitin also forms the structural support for the cell walls of many fungi.

 

C. Lipids — Diverse Hydrophobic Molecules

·      Lipids are an exception among macromolecules because they do not have polymers.

·      The unifying feature of lipids is that they all have little or no affinity for water.

·      This is because their structures are dominated by nonpolar covalent bonds.

·      Lipids are highly diverse in form and function.

 

1. Fats store large amounts of energy

·      Although fats are not strictly polymers, they are large molecules assembled from smaller molecules by dehydration reactions.

·      A fat is constructed from two kinds of smaller molecules, glycerol and fatty acids.

·      Glycerol consists of a three-carbon skeleton with a hydroxyl group attached to each.

·      A fatty acid consists of a carboxyl group attached to a long carbon skeleton, often 16 to 18 carbons long.

·      The many nonpolar C-H bonds in the long hydrocarbon skeleton make fats hydrophobic.

·      In a fat, three fatty acids are joined to glycerol by an ester linkage, creating a triacylglycerol.

·      The three fatty acids in a fat can be the same or different.

·      Fatty acids may vary in length (number of carbons) and in the number and locations of double bonds.

·      If there are no carbon-carbon double bonds, then the molecule is a saturated fatty acid — a hydrogen at every possible position.

·      If there are one or more carbon-carbon double bonds, then the molecule is an unsaturated fatty acid — formed by the removal of hydrogen atoms from the carbon skeleton.

·      Saturated fatty acids are straight chains, but unsaturated fatty acids have a kink wherever there is a double bond.

·      Fats with saturated fatty acids are saturated fats.

·      Most animal fats are saturated.

·      Saturated fats are solid at room temperature.

·      A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis) through plaque deposits.

·      Fats with unsaturated fatty acids are unsaturated fats.

·      Plant and fish fats, known as oils, are liquid are room temperature.

·      The kinks provided by the double bonds prevent the molecules from packing tightly together.

·      The major function of fats is energy storage.

·      A gram of fat stores more than twice as much energy as a gram of a polysaccharide.

·      Plants use starch for energy storage when mobility is not a concern but use oils when dispersal and packing is important, as in seeds.

·      Humans and other mammals store fats as long-term energy reserves in adipose cells.

·      Fat also functions to cushion vital organs.

·      A layer of fats can also function as insulation.

·      This subcutaneous layer is especially thick in whales, seals, and most other marine mammals.

 

2. Phospholipids are major components of cell membranes

·      Phospholipids have two fatty acids attached to glycerol and a phosphate group at the third position.

·      The phosphate group carries a negative charge.

·      Additional smaller groups may be attached to the phosphate group.

·      The interaction of phospholipids with water is complex.

·      The fatty acid tails are hydrophobic, but the phosphate group and its attachments form a hydrophilic head.

·      When phospholipids are added to water, they self-assemble into aggregates with the hydrophobic tails pointing toward the center and the hydrophilic heads on the outside.

·      This type of structure is called a micelle.

·      At the surface of a cell phospholipids are arranged as a bilayer.

·      Again, the hydrophilic heads are on the outside in contact with the aqueous solution and the hydrophobic tails from the core.

·      The phospholipid bilayer forms a barrier between the cell and the external environment.

·      They are the major component of membranes.

 

 

3. Steroids include cholesterol and certain hormones

·      Steroids are lipids with a carbon skeleton consisting of four fused carbon rings.

·      Different steroids are created by varying functional groups attached to the rings.

·      Cholesterol, an important steroid, is a component in animal cell membranes.

·      Cholesterol is also the precursor from which all other steroids are synthesized.

·      Many of these other steroids are hormones, including the vertebrate sex hormones.

·      While cholesterol is clearly an essential molecule, high levels of cholesterol in the blood may contribute to cardiovascular disease.

 

D. Proteins — Many Structures, Many Functions

·      Proteins are instrumental in about everything that an organism does.

·      These functions include structural support, storage, transport of other substances, intercellular signaling, movement, and defense against foreign substances.

·      Proteins are the overwhelming enzymes in a cell and regulate metabolism by selectively accelerating chemical reactions.

·      Humans have tens of thousands of different proteins, each with their own structure and function.

·      Proteins are the most structurally complex molecules known.

·      Each type of protein has a complex three-dimensional shape or conformation.

·      All protein polymers are constructed from the same set of 20 monomers, called amino acids.

·      Polymers of proteins are called polypeptides.

·      A protein consists of one or more polypeptides folded and coiled into a specific conformation.

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

·      Amino acids consist of four components attached to a central carbon, the alpha carbon.

·      These components include a hydrogen atom, a carboxyl group, an amino group, and a variable R group (or side chain).

·      Differences in R groups produce the 20 different amino acids.

·      The twenty different R groups may be as simple as a hydrogen atom (as in the amino acid glutamine) to a carbon skeleton with various functional groups attached.

·      The physical and chemical characteristics of the R group determine the unique characteristics of a particular amino acid.

·      One group of amino acids has hydrophobic R groups.

·      Another group of amino acids has polar R groups, making them hydrophilic.

·      The last group of amino acids includes those with functional groups that are charged (ionized) at cellular pH.

·      Some R groups are bases, others are acids.

·      Amino acids are joined together when a dehydration reaction removes a hydroxyl group from the carboxyl end of one amino acid and a hydrogen from the amino group of another.

·      The resulting covalent bond is called a peptide bond.

·      Repeating the process over and over creates a long polypeptide chain.

·      At one end is an amino acid with a free amino group the (the N-terminus) and at the other is an amino acid with a free carboxyl group the (the C-terminus).

·      The repeated sequence (N-C-C) is the polypeptide backbone.

·      Attached to the backbone are the various R groups.

·      Polypeptides range in size from a few monomers to thousands.

 

2. A protein’s function depends on its specific conformation

·      A functional protein consists of one or more polypeptides that have been precisely twisted, folded, and coiled into a unique shape.

·      It is the order of amino acids that determines what the three-dimensional conformation will be.

·      A protein’s specific conformation determines its function.

·      In almost every case, the function depends on its ability to recognize and bind to some other molecule.

·      For example, antibodies bind to particular foreign substances that fit their binding sites.

·      Enzymes recognize and bind to specific substrates, facilitating a chemical reaction.

·      Neurotransmitters pass signals from one cell to another by binding to receptor sites on proteins in the membrane of the receiving cell.

·      The folding of a protein from a chain of amino acids occurs spontaneously.

·      The function of a protein is an emergent property resulting from its specific molecular order.

·      Three levels of structure: primary, secondary, and tertiary structure, are used to organize the folding within a single polypeptide.

·      Quaternary structure arises when two or more polypeptides join to form a protein.

·      The primary structure of a protein is its unique sequence of amino acids.

·      Lysozyme, an enzyme that attacks bacteria, consists on a polypeptide chain of 129 amino acids.

·      The precise primary structure of a protein is determined by inherited genetic information.

·      Even a slight change in primary structure can affect a protein’s conformation and ability to function.

·      In individuals with sickle cell disease, abnormal hemoglobins, oxygen-carrying proteins, develop because of a single amino acid substitution.

·      These abnormal hemoglobins crystallize, deforming the red blood cells and leading to clogs in tiny blood vessels.

·      The secondary structure of a protein results from hydrogen bonds at regular intervals along the polypeptide backbone.

·      Typical shapes that develop from secondary structure are coils (an alpha helix) or folds (beta pleated sheets).

·      The structural properties of silk are due to beta pleated sheets.

·      The presence of so many hydrogen bonds makes each silk fiber stronger than steel.

·      Tertiary structure is determined by a variety of interactions among R groups and between R groups and the polypeptide backbone.

·      These interactions include hydrogen bonds among polar and/or charged areas, ionic bonds between charged R groups, and hydrophobic interactions and van der Waals interactions among hydrophobic R groups.

·      While these three interactions are relatively weak, disulfide bridges, strong covalent bonds that form between the sulfhydryl groups (SH) of cysteine monomers, stabilize the structure.

·      Quaternary structure results from the aggregation of two or more polypeptide subunits.

·      Collagen is a fibrous protein of three polypeptides that are supercoiled like a rope.

·      This provides the structural strength for their role in connective tissue.

·      Hemoglobin is a globular protein with two copies of two kinds of polypeptides.

·      A protein’s conformation can change in response to the physical and chemical conditions.

·      Alterations in pH, salt concentration, temperature, or other factors can unravel or denature a protein.

·      These forces disrupt the hydrogen bonds, ionic bonds, and disulfide bridges that maintain the protein’s shape.

·      Some proteins can return to their functional shape after denaturation, but others cannot, especially in the crowded environment of the cell.

 

·      In spite of the knowledge of the three-dimensional shapes of over 10,000 proteins, it is still difficult to predict the conformation of a protein from its primary structure alone.

·      Most proteins appear to undergo several intermediate stages before reaching their “mature” configuration.

·      The folding of many proteins is protected by chaperonin proteins that shield out bad influences.

·      A new generation of supercomputers is being developed to generate the conformation of any protein from its amino acid sequence or even its gene sequence.

·      Part of the goal is to develop general principles that govern protein folding.

·      At present, scientists use X-ray crystallography to determine protein conformation.

·      This technique requires the formation of a crystal of the protein being studied.

·      The pattern of diffraction of an X-ray by the atoms of the crystal can be used to determine the location of the atoms and to build a computer model of its structure.

 

E. Nucleic Acids -- Informational Polymers

·      The amino acid sequence of a polypeptide is programmed by a gene.

·      A gene consists of regions of DNA, a polymer of nucleic acids.

·      DNA (and their genes) is passed by the mechanisms of inheritance.

 

1. Nucleic acids store and transmit hereditary information

·      There are two types of nucleic acids: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

·      DNA provides direction for its own replication.

·      DNA also directs RNA synthesis and, through RNA, controls protein synthesis.

·      Organisms inherit DNA from their parents.

·      Each DNA molecule is very long and usually consists of hundreds to thousands of genes.

·      When a cell reproduces itself by dividing, its DNA is copied and passed to the next generation of cells.

·      While DNA has the information for all the cell’s activities, it is not directly involved in the day to day operations of the cell.

·      Proteins are responsible for implementing the instructions contained in DNA.

·      Each gene along a DNA molecule directs the synthesis of a specific type of messenger RNA molecule (mRNA).

·      The mRNA interacts with the protein-synthesizing machinery to direct the ordering of amino acids in a polypeptide.

·      The flow of genetic information is from DNA -> RNA -> protein.

·      Protein synthesis occurs in cellular structures called ribosomes.

·      In eukaryotes, DNA is located in the nucleus, but most ribosomes are in the cytoplasm with mRNA as an intermediary.

 

2. A nucleic acid strand is a polymer of nucleotides

·      Nucleic acids are polymers of monomers called nucleotides.

·      Each nucleotide consists of three parts: a nitrogen base, a pentose sugar, and a phosphate group.

·      The nitrogen bases, rings of carbon and nitrogen, come in two types: purines and pyrimidines.

·      Pyrimidines have a single six-membered ring.

·      The three different pyrimidines, cytosine (C), thymine (T), and uracil (U) differ in atoms attached to the ring.

·      Purine have a six-membered ring joined to a five-membered ring.

·      The two purines are adenine (A) and guanine (G).

 

·      The pentose joined to the nitrogen base is ribose in nucleotides of RNA and deoxyribose in DNA.

·      The only difference between the sugars is the lack of an oxygen atom on carbon two in deoxyribose.

·      The combination of a pentose and nucleic acid is a nucleoside.

·      The addition of a phosphate group creates a nucleoside monophosphate or nucleotide.

·      Polynucleotides are synthesized by connecting the sugars of one nucleotide to the phosphate of the next with a phosphodiester link.

·      This creates a repeating backbone of sugar-phosphate units with the nitrogen bases as appendages.

·      The sequence of nitrogen bases along a DNA or mRNA polymer is unique for each gene.

·      Genes are normally hundreds to thousands of nucleotides long.

·      The number of possible combinations of the four DNA bases is limitless.

·      The linear order of bases in a gene specifies the order of amino acids - the primary structure of a protein.

·      The primary structure in turn determines three-dimensional conformation and function.

 

3. Inheritance is based on replication of the DNA double helix

·      An RNA molecule is a single polynucleotide chain.

·      DNA molecules have two polynucleotide strands that spiral around an imaginary axis to form a double helix.

·      The double helix was first proposed as the structure of DNA in 1953 by James Watson and Francis Crick.

·      The sugar-phosphate backbones of the two polynucleotides are on the outside of the helix.

·      Pairs of nitrogenous bases, one from each strand, connect the polynucleotide chains with hydrogen bonds.

·      Most DNA molecules have thousands to millions of base pairs.

·      Because of their shapes, only some bases are compatible with each other.

·      Adenine (A) always pairs with thymine (T) and guanine (G) with cytosine (C).

·      With these base-pairing rules, if we know the sequence of bases on one strand, we know the sequence on the opposite strand.

·      The two strands are complementary.

·      During preparations for cell division each of the strands serves as a template to order nucleotides into a new complementary strand.

·      This results in two identical copies of the original double-stranded DNA molecule.

·      The copies are then distributed to the daughter cells.

·      This mechanism ensures that the genetic information is transmitted whenever a cell reproduces.

 

4. We can use DNA and proteins as tape measures of evolution

·      Genes (DNA) and their products (proteins) document the hereditary background of an organism.

·      Because DNA molecules are passed from parents to offspring, siblings have greater similarity than do unrelated individuals of the same species.

·      This argument can be extended to develop a “molecular genealogy” between species.

·      Two species that appear to be closely related based on fossil and molecular evidence should also be more similar in DNA and protein sequences than are more distantly related species.

·      In fact, the sequence of amino acids in hemoglobin molecules differs by only one amino acid between humans and gorilla.

·      More distantly related species have more differences.