The Structure and Function of Macromolecules Chapter 3 The Structure and Function of Macromolecules

The Molecules of Life Overview: Another level in the hierarchy of biological organization is reached when small organic molecules are joined together Atom ---> molecule --- compound

Macromolecules Are large molecules composed of smaller molecules Are complex in their structures

Macromolecules Most macromolecules are polymers, built from monomers Four classes of life’s organic molecules are polymers Carbohydrates Proteins Nucleic acids Lipids

A polymer Is a long molecule consisting of many similar building blocks called monomers Specific monomers make up a macromolecule E.g. amino acids are the monomers for proteins

The Synthesis and Breakdown of Polymers Monomers form larger molecules by condensation reactions called dehydration synthesis Dehydration reaction in the synthesis of a polymer HO H 1 2 3 4 H2O Short polymer Unlinked monomer Longer polymer Dehydration removes a water molecule, forming a new bond

The Synthesis and Breakdown of Polymers Polymers can disassemble by Hydrolysis (addition of water molecules) Hydrolysis of a polymer HO 1 2 3 H 4 H2O Hydrolysis adds a water molecule, breaking a bond

Although organisms share the same limited number of monomer types, each organism is unique based on the arrangement of monomers into polymers An immense variety of polymers can be built from a small set of monomers Enzymes facilitate their synthesis

Carbohydrates Serve as fuel (4 calories/g) and building material Include both sugars and their polymers (starch, cellulose, etc.)

Sugars Monosaccharides Are the simplest sugars Can be used for fuel Can be converted into other organic molecules Can be combined into polymer of CH2O Have a carbonyl group (aldoses and ketoses) and all other C’s have a hydroxyl group

Examples of monosaccharides Triose sugars (C3H6O3) Pentose sugars (C5H10O5) Hexose sugars (C6H12O6) H C OH H C OH HO C H H C OH C O HO C H H C O Aldoses Glyceraldehyde Ribose Glucose Galactose Dihydroxyacetone Ribulose Ketoses Fructose

Though often drawn as linear skeletons, in aqueous solutions, Monosaccharides May be linear Can form rings The numbering starts to the right of the oxygen! H H C OH HO C H H C O C 1 2 3 4 5 6 OH 4C 6CH2OH 5C H OH 2 C 1C 3 C 2C 1 C CH2OH HO 3 2 Though often drawn as linear skeletons, in aqueous solutions, most sugars form rings

Disaccharides Consist of two monosaccharides Are joined by a glycosidic linkage (covalent bond formed between two monosaccharides by dehydration synthesis)

Dehydration reaction in the synthesis of maltose Dehydration reaction in the synthesis of maltose. The bonding of two glucose units forms maltose. The glycosidic link joins the number 1 carbon of one glucose to the number 4 carbon of the second glucose. Joining the glucose monomers in a different way would result in a different disaccharide. Dehydration reaction in the synthesis of sucrose. Sucrose is a disaccharide formed from glucose and fructose. Notice that fructose, though a hexose like glucose, forms a five-sided ring. (a) (b) H HO H OH OH O CH2OH H2O 1 2 4 1– 4 glycosidic linkage 1–2 glycosidic linkage Glucose Fructose Maltose Sucrose

Polysaccharides Polysaccharides Are polymers of sugars (few hundred to 1000’s monosaccharides!) Serve many roles in organisms The structure and function of polysaccharides are determined by its sugar monomers and by the positions of its glycosidic linkages

Storage Polysaccharides Chloroplast Starch Amylose Amylopectin 1 μm Starch: a plant polysaccharide Starch Is a polymer consisting entirely of glucose monomers Is the major storage form of glucose in plants

Storage Polysaccharides It is a heteropolysaccharide: Amylose with 1,4 linkages is unbranched and helical (20-30%) Amylopectin has 1,4 and 1,6 linkages with branching (70-80%)

Storage Polysaccharides Glycogen Consists of glucose monomers Made of only one molecule Is the major storage form of glucose in animals Like amylopectin, but more extensively branched

Structural Polysaccharides Cellulose Is a polymer of glucose Is the most abundant organic compound! Formed from  glucose, which has a slightly different ring structure than  glucose; when monomers join, every other monomer is upside down with respect to its neighbors (picture coming on next slide!)

Has different glycosidic linkages than starch (c) Cellulose: 1– 4 linkage of β glucose monomers H O CH2OH OH HO 4 C 1 (a) α and β glucose ring structures (b) Starch: 1– 4 linkage of α glucose monomers α glucose β glucose Polymers with  glucose are helical Polymers with  glucose are straight

In straight structures, H atoms on one strand can bond with OH groups on other strands Parallel cellulose molecules held together this way are grouped into microfibrils, which form strong building materials for plants Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Is a major component of the tough walls that enclose plant cells Cell walls Cellulose microfibrils in a plant cell wall ∩ Microfibril CH2OH OH O Glucose monomer Parallel cellulose molecules are held together by hydrogen bonds between hydroxyl groups attached to carbon atoms 3 and 6. About 80 cellulose molecules associate to form a microfibril, the main architectural unit of the plant cell wall. A cellulose molecule is an unbranched glucose polymer. Cellulose molecules

Cellulose is difficult to digest Most organisms lack enzymes to hydrolize the  linkages Cows have microbes in their stomachs to facilitate this process

Chitin, another important structural polysaccharide Is found in the exoskeleton of arthropods and cell walls of fungi Can be used as surgical thread (a) The structure of the chitin monomer. O CH2OH OH H NH C CH3 (b) Chitin forms the exoskeleton of arthropods. This cicada is molting, shedding its old exoskeleton and emerging in adult form. (c) Chitin is used to make a strong and flexible surgical thread that decomposes after the wound or incision heals.

Lipids Lipids are a diverse group of hydrophobic molecules Lipids Are the one class of large biological molecules that do not consist of polymers Share the common trait of being hydrophobic; composed mostly of hydrocarbons, which are nonpolar

Fats Fats are constructed from two types of smaller molecules: glycerol and fatty acids Function: Energy storage (9 calories/g) Glycerol is a three-carbon alcohol with a hydroxyl group attached to each carbon A fatty acid consists of a carboxyl group attached to a long carbon skeleton Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fatty acid (palmitic acid) Fig. 5-11 Fatty acid (palmitic acid) Glycerol (a) Dehydration reaction in the synthesis of a fat Ester linkage (bond between a hydroxyl and carboxyl group) Figure 5.11 The synthesis and structure of a fat, or triacylglycerol (b) Fat molecule (triacylglycerol)

Unsaturated fatty acids have one or more double bonds The fatty acids can be the same or there can be two or three different kinds Fatty acids vary in length (number of carbons) and in the number and locations of double bonds Saturated fatty acids have the maximum number of hydrogen atoms possible and no double bonds Unsaturated fatty acids have one or more double bonds Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Saturated fat and fatty acid Saturated fatty acids Have the maximum number of hydrogen atoms possible Have no double bonds; their flexibility allows them to pack tightly Solid at room temperature Saturated fat and fatty acid Stearic acid

Unsaturated fat and fatty acid Unsaturated fatty acids Have one or more double bonds Liquid at room temperature Unsaturated fat and fatty acid Oleic acid

Trans Fats Uncommon in nature Formed by hydrogenating unsaturated fats (make peanut butter, margarine, cool whip, etc) Contribute to atherosclerosis

Phospholipids Have only two fatty acids Have a phosphate group instead of a third fatty acid

Phospholipid structure Consists of a hydrophilic “head” (phosphate group is charged)and hydrophobic “tails” CH2 O P CH C Phosphate Glycerol (a) Structural formula (b) Space-filling model Fatty acids (c) Phospholipid symbol Hydrophobic tails Hydrophilic head Hydrophobic tails – Hydrophilic head Choline + N(CH3)3

The structure of phospholipids Results in a bilayer arrangement found in cell membranes Hydrophilic head WATER Hydrophobic tail

Steroids Steroids Are lipids characterized by a carbon skeleton consisting of four fused rings

One steroid, cholesterol Is found in cell membranes Is a precursor for some hormones; some steroids are hormones High levels in blood can contribute to atherosclerosis HO CH3 H3C

Proteins Proteins have many structures, resulting in a wide range of functions Account for more than ½ of the dry mass of most cells Proteins do most of the work in cells and act as enzymes Proteins are made of monomers called amino acids

Enzymes Are a type of protein that acts as a catalyst, speeding up chemical reactions Substrate (sucrose) Enzyme (sucrase) Glucose OH H O H2O Fructose 3 Substrate is converted to products. 1 Active site is available for a molecule of substrate, the reactant on which the enzyme acts. Substrate binds to enzyme. 2 4 Products are released.

Polypeptides Polypeptides A protein Are polymers (chains) of amino acids A protein Consists of one or more polypeptides

Amino acids Are organic molecules possessing both carboxyl and amino groups Differ in their properties due to differing side chains, called R groups

Twenty Amino Acids 20 different amino acids make up proteins O O– H H3N+ C CH3 CH CH2 NH H2C H2N Nonpolar Glycine (Gly) Alanine (Ala) Valine (Val) Leucine (Leu) Isoleucine (Ile) Methionine (Met) Phenylalanine (Phe) Tryptophan (Trp) Proline (Pro) H3C S 20 different amino acids make up proteins

Polar Electrically charged Serine (Ser) Threonine (Thr) Cysteine (Cys) OH CH2 C H H3N+ O CH3 CH SH NH2 Polar Electrically charged –O NH3+ NH2+ NH+ NH Serine (Ser) Threonine (Thr) Cysteine (Cys) Tyrosine (Tyr) Asparagine (Asn) Glutamine (Gln) Acidic Basic Aspartic acid (Asp) Glutamic acid (Glu) Lysine (Lys) Arginine (Arg) Histidine (His)

Amino Acid Polymers Amino acids Are linked by peptide bonds

Protein Conformation and Function A protein’s specific conformation (shape) determines how it functions

Four Levels of Protein Structure Primary structure Is the unique sequence of amino acids in a polypeptide – Amino acid subunits +H3N Amino end o Carboxyl end c Gly Pro Thr Glu Seu Lys Cys Leu Met Val Asp Ala Arg Ser lle Phe His Asn Tyr Trp Lle

Secondary structure Is the folding or coiling resulting from hydrogen bonds between repeating constituents of the polypeptide backbone (not the R groups) Includes the  helix and the  pleated sheet O C α helix Amino acid subunits N H R H

Is the overall three-dimensional shape of a polypeptide Tertiary structure Is the overall three-dimensional shape of a polypeptide Results from interactions between R groups CH2 CH O H O C HO NH3+ -O S CH3 H3C Hydrophobic interactions and van der Waals interactions Polypeptide backbone Hyrdogen bond Ionic bond Disulfide bridge

Quaternary structure Is the overall protein structure that results from the aggregation of two or more polypeptide subunits Polypeptide chain Collagen β Chains α Chains Hemoglobin Iron Heme

Review of Protein Structure +H3N Amino end Amino acid subunits α helix

Sickle-Cell Disease: A Simple Change in Primary Structure Results from a single amino acid substitution in the protein hemoglobin

. . . Primary structure Secondary and tertiary structures Quaternary structure Function Red blood cell shape Hemoglobin A Molecules do not associate with one another, each carries oxygen. Normal cells are full of individual hemoglobin molecules, each carrying oxygen α β 10 μm Hemoglobin S Molecules interact with one another to crystallize into a fiber, capacity to carry oxygen is greatly reduced. β subunit 1 2 3 4 5 6 7 Normal hemoglobin Sickle-cell hemoglobin . . . Exposed hydrophobic region Val Thr His Leu Pro Glul Glu Fibers of abnormal hemoglobin deform cell into sickle shape.

What Determines Protein Conformation? Protein conformation depends on the physical and chemical conditions of the protein’s environment Temperature, pH, etc. affect protein structure

Denaturation is when a protein unravels and loses its native conformation (shape) Renaturation Denatured protein Normal protein

The Protein-Folding Problem Most proteins Probably go through several intermediate states on their way to a stable conformation Denaturated proteins no longer work in their unfolded condition Proteins may be denaturated by extreme changes in pH or temperature

Chaperonins Are protein molecules that assist in the proper folding of other proteins Keeps the protein separated from other molecules in the cytoplasm while folding Hollow cylinder Cap Chaperonin (fully assembled) Steps of Chaperonin Action: An unfolded poly- peptide enters the cylinder from one end. The cap attaches, causing the cylinder to change shape in such a way that it creates a hydrophilic environment for the folding of the polypeptide. The cap comes off, and the properly folded protein is released. Correctly folded protein Polypeptide 2 1 3

Misfolding of Proteins Is a serious problem Alzheimer’s and Parkinson’s diseases are associated with accumulation of misfolded proteins

Nucleic Acids Nucleic acids store and transmit hereditary information Genes Are the units of inheritance Program the amino acid sequence of polypeptides Are made of nucleotide sequences on DNA

Nucleic Acids Made of nucleotide monomers There are two types of nucleic acids Deoxyribonucleic acid (DNA) Ribonucleic acid (RNA)

Deoxyribonucleic Acid DNA Stores information for the synthesis of specific proteins Found in the nucleus of cells Comprised of two strands Sugar is deoxyribose Bases are A,T,C,G

Ribonucleic Acid RNA Helps convert the information contained in DNA into functional gene products, like proteins Is single stranded and does not stay in the nucleus Has ribose sugar and U replaces T 3 types: mRNA, rRNA, tRNA

Synthesis of mRNA in the nucleus DNA Functions Directs RNA synthesis (transcription) Directs protein synthesis through RNA (translation) 1 2 3 Synthesis of mRNA in the nucleus Movement of mRNA into cytoplasm via nuclear pore Synthesis of protein NUCLEUS CYTOPLASM DNA mRNA Ribosome Amino acids Polypeptide

The Structure of Nucleic Acids 5’ end 5’C 3’ end OH O Nucleic acids Exist as polymers called polynucleotides Polynucleotide, or nucleic acid

Each polynucleotide Consists of monomers called nucleotides Sugar + phosphate + nitrogen base Nitrogenous base Nucleoside O O− −O P CH2 5’C 3’C Phosphate group Pentose sugar (b) Nucleotide

Nucleotide Monomers Nucleotide monomers Are made up of nucleosides (sugar + base) and phosphate groups CH Uracil (in RNA) U Ribose (in RNA) Nitrogenous bases Pyrimidines C N O H NH2 HN CH3 Cytosine Thymine (in DNA) T HC NH Adenine A Guanine G Purines HOCH2 OH Pentose sugars Deoxyribose (in DNA) 4’ 5” 3’ 2’ 1’ (c) Nucleoside components

A,T,C,G The nitrogenous bases in DNA Form hydrogen bonds in a complementary fashion (A with T only, and C with G only)

Nitrogen bases A and G are purines C,T and U are pyrimidines Have two rings C,T and U are pyrimidines Have one ring

Nucleotide Monomers A-T forms double bond C-G forms triple bond

Nucleotide Polymers Nucleotide polymers Are made up of nucleotides linked by the–OH group on the 3´ carbon of one nucleotide and the phosphate on the 5´ carbon on the next

DNA Strands are antiparallel LE 10-5b DNA Strands are antiparallel 5’ end terminates in P group 3’ end terminates in sugar 5 end 3 end P HO 5¢ 4¢ 2¢ 3¢ A T 3¢ 1¢ 1¢ 2¢ 4¢ 5¢ P P P C G P P G C P P T A OH P 3 end 5 end

The DNA double helix Consists of two antiparallel nucleotide strands 3’ end Sugar-phosphate backbone Base pair (joined by hydrogen bonding) Old strands Nucleotide about to be added to a new strand A 5’ end New strands

Chargaff’s Rule In DNA, there is always equality in quantity between the bases A and T and between the bases C and G If a sample of DNA is found to contain 20% T, what is the approximate % of the other three nucleotides in the sample?

DNA and Proteins as Tape Measures of Evolution Molecular comparisons Help biologists sort out the evolutionary connections among species

Which species are most closely related?

The Theme of Emergent Properties in the Chemistry of Life: A Review Higher levels of organization Result in the emergence of new properties Organization Is the key to the chemistry of life