Chapter 3 Biochemistry

Why study carbon? All living things are made of cells Cells are… ~72% water ~3% salts ~25% carbon compounds Carbohydrates Proteins Lipids Nucleic acids

Carbon Chemistry Organic chemistry -study of carbon compounds Carbon atoms can form diverse molecules by bonding to four other atoms Carbon has four valence electrons and may form single, double, triple, or quadruple bonds

The electron configuration of carbon gives it covalent compatibility with many different elements Hydrogen (valence = 1) Oxygen (valence = 2) Nitrogen (valence = 3) Carbon (valence = 4)

Hydrocarbons Hydrocarbons are molecules consisting of only carbon and hydrogen Hydrocarbons are found in many of a cell’s organic molecules

H C (a) Length (b) Branching (c) Double bonds (d) Rings Ethane Propane Butane isobutane 1-Butene 2-Butene Cyclohexane Benzene

Functional Groups Functional groups are the parts of molecules involved in chemical reactions They Are the chemically reactive groups of atoms within an organic molecule Give organic molecules distinctive chemical properties CH3 OH HO O Estradiol Testosterone Female lion Male lion

Six functional groups are important in the chemistry of life Hydroxyl – in alcohols, sugar Carbonyl – in sugars, amino acids, nucleotide bases Carboxyl – in amino acids, fatty acids; acts as an acid and releases H+ Amino – in amino acids; acts as a weak base Sulfhydryl – in amino acid cysteine; helps stabilize protein structure Phosphate – in ATP, nucleotides, proteins, phospholipids; acidic;

Some important functional groups of organic compounds STRUCTURE (may be written HO ) HYDROXYL CARBONYL CARBOXYL OH In a hydroxyl group (—OH), a hydrogen atom is bonded to an oxygen atom, which in turn is bonded to the carbon skeleton of the organic molecule. (Do not confuse this functional group with the hydroxide ion, OH–.) When an oxygen atom is double-bonded to a carbon atom that is also bonded to a hydroxyl group, the entire assembly of atoms is called a carboxyl group (—COOH). C O The carbonyl group ( CO) consists of a carbon atom joined to an oxygen atom by a double bond. 

Some important functional groups of organic compounds The amino group (—NH2) consists of a nitrogen atom bonded to two hydrogen atoms and to the carbon skeleton. AMINO SULFHYDRYL PHOSPHATE (may be written HS ) The sulfhydryl group consists of a sulfur atom bonded to an atom of hydrogen; resembles a hydroxyl group in shape. In a phosphate group, a phosphorus atom is bonded to four oxygen atoms; one oxygen is bonded to the carbon skeleton; two oxygens carry negative charges; abbreviated P . The phosphate group (—OPO32–) is an ionized form of a phosphoric acid group (—OPO3H2; note the two hydrogens). N H SH O P OH

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 each macromolecule E.g. amino acids are the monomers for proteins

How are organic compounds built? Enzymes (proteins) are needed to make metabolic reactions proceed much faster than they would on their own.

The Synthesis and Breakdown of Polymers Monomers form larger molecules by condensation reactions called dehydration synthesis (a) 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 a cleavage reaction -Hydrolysis (addition of water molecules) (b) Hydrolysis of a polymer HO 1 2 3 H 4 H2O Hydrolysis adds a water molecule, breaking a bond

Carbohydrates Serve as fuel 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 polymers

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

Monosaccharides May be linear Can form rings 4C 3 2 OH 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 (a) Linear and ring forms. Chemical equilibrium between the linear and ring structures greatly favors the formation of rings. To form the glucose ring, carbon 1 bonds to the oxygen attached to carbon 5.

Disaccharides Consist of two monosaccharides Are joined by a glycosidic linkage

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 (complex carbohydrates) Are polymers of sugars Serve many roles in organisms

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

(b) Glycogen: an animal polysaccharide Consists of glucose monomers Is the major storage form of glucose in animals Mitochondria Giycogen granules 0.5 m (b) Glycogen: an animal polysaccharide Glycogen

Structural Polysaccharides Cellulose Is a polymer of glucose Its bonding arrangement stabilizes the chains and make it resist being digested

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

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 Cows have microbes in their stomachs to facilitate this process

Chitin, another important structural polysaccharide Is found in the exoskeleton of arthropods Can be used as surgical thread Has a nitrogen group (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

Fats Are constructed from two types of smaller molecules, a single glycerol and usually three fatty acids Vary in the length and number and locations of double bonds they contain

(a) Saturated fat and fatty acid Saturated fatty acids Have the maximum number of hydrogen atoms possible Have no double bonds (a) Saturated fat and fatty acid Stearic acid

(b) Unsaturated fat and fatty acid Unsaturated fatty acids Have one or more double bonds (b) Unsaturated fat and fatty acid cis double bond causes bending Oleic acid

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

(a) Structural formula (b) Space-filling model Phospholipid structure Consists of a hydrophilic “head” 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

Sterols Sterols (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 HO CH3 H3C

Proteins Proteins have many structures, resulting in a wide range of functions Proteins do most of the work in cells and act as enzymes Proteins are made of monomers called amino acids

An overview of protein functions

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.

Enzymes vs catalyst

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 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 of the polypeptide into a repeating configuration Includes the  helix and the  pleated sheet O C  helix  pleated sheet 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 amino acids and 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  Chains  Chains Hemoglobin Iron Heme

Review of Protein Structure +H3N Amino end Amino acid subunits helix

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

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

Sickle-cell 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   10 m Hemoglobin S Molecules interact with one another to crystallize into a fiber, capacity to carry oxygen is greatly reduced.  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.

Nucleotides Consist of sugar, phosphate group, and nitrogen-containing bases ATP – adenosine triphosphate contains 3 phosphate groups; important source of energy Coenzymes – enzyme helpers that accept hydrogen atoms and electrons

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

The Roles of Nucleic Acids 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

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 (a) 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