Chapter 5 Structure and Function of Large Biological Molecules
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Transcript of Chapter 5 Structure and Function of Large Biological Molecules
Chapter 5Structure and Function of Large
Biological Molecules
What are the Molecules of Life?
– Because life is so complex, we would assume that there are numbers of molecules
– This is not the case• The large molecules of all living things fall into four
main clases– Carbohydrates– Lipids– Proteins– Nucleic acids
What are macromolecules?
– Huge– Molecules that are very large and complex– Exhibit unique emergent properties due to the
orderly arrangement of their atoms
What are polymers?
– Chain-like molecules– Long molecule consisting of many similar or
identical building blocks linked by covalent bonds– Macromolecules in three of the four classes of
life’s organic compounds• Carbohydrates• Proteins• Nucleic acids
What are monomers?
– Repeating units that serve as the building blocks of a polymer
– Smaller molecules
What’s different about the polymers?
• Classes of polymers differ in the nature of their monomers
What’s similar about the polymers?
– The chemical mechanisms by which cells make and break down polymers are basically the same in all cases
What is a condensation reaction?
– Monomers are connected by this type of reaction– Two molecules are covalently bonded to each
other through loss of a water molecule
What is a dehydration reaction?– A specific condensation reaction– Because water is the molecule that is lost– When a bond forms between two monomers, each
monomer contributes part of the water molecule that is lost• One molecule provides a hydroxyl group (-OH)• The other provides a hydrogen (- H)
– Reaction can be repeated as monomers are added to the chain one by one, making a polymer
– Facilitated by enzymes• Specialized macromolecules that speed up chemical
reactions in cells
What is hydrolysis?
– Polymers are disassembled to monomers through this process
– Reverse of dehydration reaction– Means “to break using water”– Bonds between the monomers are broken by the
addition of water molecules• Hydrogen from water attaching to one monomer• Hydroxyl group attaching to the adjacent monomer
What is an example of hydrolysis?
• Digestion
Dehydration and HydrolysisReactions
Short polymer Unlinked monomer
Dehydration removes a watermolecule, forming a new bond
Dehydration reaction in the synthesis of a polymerLonger polymer
Hydrolysis adds a watermolecule, breaking a bond
Hydrolysis of a polymer
Dehydration reactions in Carbohydrates
Glucose
Maltose
Fructose Sucrose
Glucose Glucose
Dehydrationreaction in thesynthesis of maltose
Dehydrationreaction in thesynthesis of sucrose
1–4glycosidic
linkage
1–2glycosidic
linkage
There exists great diversity within macromolecules:
– Between one cell to another• Even in same organism
– Between siblings variations exist– Between unrelated individuals• More and more extensive differences exist
What is the basis for this diversity?
– Macromolecules are constructed from only 40 to 50 common monomers
– Example: • Proteins are built from only 20 kinds of amino acids
arranged in chains that are hundreds of amino acids long
– SMALL MOLECULES COMMON TO ALL ORGANISMS ARE ORDERED INTO UNIQUE MACROMOLECULES
What is a carbohydrate?
– Include both sugars and polymers of sugars– Three forms• Monosaccharide• Disaccharide• Polysaccharide
What is a monosaccharide?
– Simplest of carbohydrates– Known as simple sugars– From Greek monos (meaning single) and sacchar
(meaning sugar)– Have molecular formulas that are some multiple
of the following unit:• CH2O
What is a monosaccharide?
• Example:–C6H12O6
–The most common monosaccharide–Of central importance to the chemistry of
life–Aldose
What is the structure of a sugar?• Has carbonyl group
– >C=O• multiple hydroxyl groups
– - OH
CarbohydratesSee the Carbonyls and Hydroxides?
Dehydration reactions in Carbohydrates
Glucose
Maltose
Fructose Sucrose
Glucose Glucose
Dehydrationreaction in thesynthesis of maltose
Dehydrationreaction in thesynthesis of sucrose
1–4glycosidic
linkage
1–2glycosidic
linkage
What distinguishes between sugars?
– Can be either aldose (aldehyde sugar) or ketose (ketone sugar)
– Can also classify sugars by the size of the carbon skeleton
– Can also be diversified based on spatial arrangement
What distinguishes between sugars?
– Can be either aldose (aldehyde sugar) or ketose (ketone sugar)• Glucose is an aldose
What distinguishes between sugars?
– Can be either aldose (aldehyde sugar) or ketose (ketone sugar)
– Can also classify sugars by the size of the carbon skeleton• Ranges from 3 to 7 carbons long• Examples:
– Hexoses» Glucose and fructose» Have six carbons
– What’s an example of a triose?– What’s an example of a pentose?
What distinguishes between sugars?
– Can be either aldose (aldehyde sugar) or ketose (ketone sugar)
– Can also classify sugars by the size of the carbon skeleton
– Can also be diversified based on spatial arrangement• Arrangement around asymmetrical carbon• Example:
– Glucose and galactose differ in placement of parts around asymmetrical carbon
– This small difference gives those carbons different shapes and behaviors
What’s the biological importance of monosaccharides?
– In cellular respiration, energy is extracted in series of reactions from glucose
– Simple sugars are major source of energy for cells
What is a disaccharide?
– Double sugars– Consist of two monosaccharides joined by a
glycosidic linkage
What is glycosidic linkage?
– Covalent bond formed between two monosaccharides by dehydration reaction
– Example:• Maltose is disaccharide formed by inking of two
molecules of glucose– Maltose is also know as a malt sugar – Used in brewing beer
• Sucrose– Table sugar– Monomers that make up it are glucose and fructose
What is a polysaccharide?
– Polymer composed of many sugar building blocks?– Macromolecules– Polymers with few hundred to a few thousand
monosaccharides joined by glycosidic linkages– Some serve as storage material that are
hydrolyzed as needed to provide sugar for cells
What is a storage polysaccharide?
– Used for storage for later use– Starch
Starch• Plant polysaccharide• Two forms– Amylose (unbranched)– Amylopectin (branched)
• Plants store starch as granules within cellular plastids– Include chloroplasts
• Polymer of glucose monomers• Allows the buildup (stockpile) of surplus glucose– Represents stored energy
• Most glucose monomers are jointed by 1 – 4 linkages– #1 carbon to #4 carbon
Starch
• Sugar can later be withdrawn from this carbohydrate “bank” hydrolysis– Breaks the bonds between the glucose monomers
• Animals also have enzymes that can hydrolyze plant starch
Light ovals in the micrograph are granules of starch within a chloroplast of a plant cell. Simplest form of starch is the amylose.
Amylopectin is more complex starch
Glycogen
• Polymer of glucose similar to polysaccharide but very branched
• Humans store this in liver and muscle cells• Hydrolysis releases glucose when the demand
for sugar increases• Cannot sustain an animal for long• Stores are depleted in about a day unless they
are replenished by consumption of food
What is a structural polysaccharide?
– Build strong materials from structural polysaccharides
– Example:• Cellulose
Cellulose in Plant Cell Walls
Cellulosemolecules
Cellulose microfibrilsin a plant cell wall
Cell walls Microfibril
Plant cells
0.5 µm
b Glucosemonomer
Cellulose• Major component of the cell walls in plant cells• Most abundant organic compound on earth• Polymer of glucose• Different glycosidic linkage than those in starch• Glucose monomers are in beta configuration– Every other glucose monomer is upside down
• Never branched• Some hydroxyl groups on its glucose monomers are
free to hydrogen – bond• In plant cell walls, parallel cellulose molecules held
together arranged into microfibrils
Cellulose
• Enzymes that digest starch by hydrolyzing its alpha linkages cannot hydrolyze the beta linkages of cellulose
• Humans cannot digest cellulose– Some animals possess enzymes that can digest
cellulose• Some prokaryotes can digest cellulose– In cows and termite guts
Chitin
• Another structural polysaccharide• Carbohydrate used by arthropods to build
exoskeleton• Leathery and flexible– Becomes hardened when encrusted with calcium
carbonate• Found in many fungi• Glucose monomer of chitin has a nitrogen-
containing appendage
Chitin
What are Lipids?• Class of large biological molecules• Does not include true polymers• Not big enough to be considered
macromolecules• Grouped together because share one
important trait• Mix poorly with water– Hydrophobic
• Consist mostly of hydrocarbon regions• Vary in form and function
Lipids
Lipids
• Include waxes and certain pigments• Most biologically important types:– Fats– Phospholipds– steroids
What are fats?
• Not polymers• Large molecules assembled from few smaller
molecules• Dehydration reactions• Constructed from 2 kinds of smaller molecules– Glycerol– Fatty acids
What are fats?
• Major function of fats is energy storage• 1 gram of fat stores more than tice as much
energy as a gram of polysaccharide (like starch)
• Stored in adipose cells
What is a glycerol?
• Alcohol with 2 carbon skeleton bearing hydroxyl group
What is a fatty acid?• Has a long carbon skeleton– Usually 16 or 18 atoms in length
• Carbon at end of fatty acid is part of carboxyl group– What gives it the name fatty acid
• Attached to the carboxyl group is a long hydrocarbon chain
• Nonpolar C – H bonds in the hydrocarbon chains of fatty acids are the reason fats are hydrophobic
Ester Linkage and Lipids
Dehydration reaction in the synthesis of a fatGlycerol
Fatty acid(palmitic acid)
Why do fats separate from water?
• Water molecules hydrogen-bond to one another and exclude the fats
• Three fatty acid molecules each join to glycerol by an ester linkage when making a fat– Also called a triacylglycerol
What is an ester linkage?
• Bond between a hydroxyl group and a carboxyl group
Triglycerol molecule
Ester linkage
What is a triacylglycerol?
• Consists of three fatty acids linked to one glycerol molecule
• Also called a triglyceride
Fatty Acids
• Vary in length• Vary in number and locations of double bonds
What is a saturated fat?
• No double bonds between carbon atoms composing the chain
• As many hydrogen atoms as possible are bonded to the carbon skeleton
• Saturated with hydrogens• At room temperature, the molecules of a saturated fat
such as butter are packed closely together• saturated fatty acids• Fat made from saturated fatty acids• Flexibility allows fat molecules to pack together tightly
What is a saturated fat?
• Lard• Butter
Saturated vs. Unsaturated
What is an unsaturated fat?• Has one or more double bonds• Formed by the removal of hydrogen atoms
from the carbon skeleton• At room temperature, molecules of an
unsaturated fat such as olive oil cannot pack together closely enough to solidify
• the kinks in some of their fatty acid hydrocarbon chains wherever a cis double bond occurs
• Kinks prevent molecules from packing closely
What is an unsaturated fat?
• Fats of plants and fishes• Referred to as oils
Saturated vs. Unsaturated
What are hydrogenated oils?
• Unsaturated fats synthetically converted to saturated fats by adding hydrogen
• Examples:– Peanut buter– Margarine– Keep from separated
What are trans fat?
• Through hydrogenating vegetable oils produces not only saturated fats but also unsaturated fats with trans double bonds
• May contribute to atherosclerosis
What are phospholipids?• Type of lipid• Essential for cells • Make up cell membranes• Similar to fat molecule• Has only two fatty acids attached to glycerol• Third hydroxyl group of glycerol is joined to
phosphate group• Has a negative electrical charge• Small molecules can be linked to the phosphate
group to form a variety of phospholipids
Phospholipid of cell membranes
What are phospholipids?• Two ends show different behavior toward
water• Tails are hydrophobic• Hydrophilic head• Self-assemble into double-layered aggregates– bilayers
What are steroids?
• Lipids characterized by a carbon skeleton consisting of four fused rings
• Vary in chemical group attached
Steroid Structure
What are cholesterol?
• Common component of animal cell membranes
• Precursor from which other steroids are synthesized
• Synthesized in liver in vertebrates• Hormones:– Sex hormones– Steroids produced from cholesterol
Proteins• Account for more than 50% of dry mass of most
cells• Instrumental in almost everything organisms do• Some speed up chemical reactions, some play
role in structural support, storage, transport, cellular communication, movement, and defense against foreign substances
• Most structurally sophisticated molecules known• Vary in structure• Have unique 3D shape• Consists of one or more polypeptides
What do Proteins do?• Some speed up chemical reactions• some play role in structural support, storage,
transport, cellular communication, movement, and defense against foreign substances
Proteins
What are enzymes?
• Most are proteins• Regulate metabolism by acting as catalysts• Can perform its function over and over again
What are catalysts?
• Chemical agents that selectively speed up chemical reactions without being consumed by the reaction
What are polypeptides?
• Polymers of amino acids• 20 different polypeptides construct amino
acids• Polypeptides are folded and coiled into a
specific 3D structure
What are Amino Acids?• Share common structure• Organic molecules possessing both carboxyl
and amino groups• At center, is an asymmetric carbon called
alpha carbon• 4 different partners:– Amino group– Carboxyl group– Hydrogen atom– Variable group (R)
LE 5-UN78
Aminogroup
Carboxylgroup
a carbon
Amino Acid Partners
• Amino and carboxyl are in ionized form because that’s how they usually exist in the pH in a cell
• R group:– R group can be a simple hydrogen atom or a carbon
skeleton with various functional groups– The physical and chemical properties of this side
chain determines the unique characteristics of a particular amino acid
– Affects the functional role in a polypeptide– Grouped according to properties of side chains
Nonpolar – Hydrophobic Amino Acids
Hydrophilic Amino Acids
Acidic vs Basic Amino Acids
Acidic have side chains that are generally negative in charge. Basic amino acids have side chains that are generally positive in charge.REFERS ONLY TO THE SIDE CHAINS
Amino Acid Polymers
• Amino acids become positioned so that carboxyl group of one is adjacent to amino group of the other
• Joined by dehydration reaction– Creates a peptide bond
• POLYPEPTIDE– Polymer of many amino acids linked by peptide
bonds– Range in length from few monomers to thousand
or more
Dehydration and Hydrolysis
Reactions again Short polymer Unlinked monomer
Dehydration removes a watermolecule, forming a new bond
Dehydration reaction in the synthesis of a polymerLonger polymer
Hydrolysis adds a watermolecule, breaking a bond
Hydrolysis of a polymer
What are the N- and C- termina?
• N-terminus– Amino end of the chain
• C-terminus– Carboxyl end of the chain
• The repeating sequence of amino group, carbon, and carboxyl group is called the polypeptide backbone
Peptide Bonding
Diversity
• The ability to make different polymers by linking the 20 amino acids into a variety of sequences
Protein structure
• Its activities depend on its 3D shape
• Polypeptide DOES NOT EQUAL Protein
• Functioning protein is not just 1 polypeptide chain but, instead, one or more polypeptides twisted, folded and coiled into a molecule with a unique shape
Protein structure
• Once the polypeptide is formed, it will spontaneously fold into the 3D shape
• The folding pattern is reinforced by the formation of bonds between different parts of the chain
• Some are spherical (globular proteins)• Some are long fibers (fibrous proteins)
Protein structure
• Specific structure determines how it works• Function is dependent on ability to recognize
and bind to another molecule
Why is this important for enzymes?
• Must recognize and bind closely to its substrate (substance that the enzyme works on)
• Lock and key• Example:– Endorphins• Heroin and morphine mimic endorphins
BUT… it all depends on the primary structure
4 Levels of Protein Structure
• Primary• Secondary• Tertiary
• Quaternary
Primary Structure
• The amino acid sequence• Primary structure is determined by inherited
genetic information
Primary (1’) sequence
Secondary
• Segments of polypeptide chains that are coiled or folded
• Coils and folds are result of hydrogen bonds between the parts of the polypeptide backbone– due to electronegative N and O with partial
negative charge– Slightly positive H attracted to O of nearby atom
What are the 2 types of secondary structures?
• a helix– Delicate coil– Held together by hydrogen bonds btw every 4th
amino acid• B pleated sheet– 2 or more regions of polypeptide side chain are
connected by hydrogen bonds btw parts of the 2 parallel polypeptide backbones
2’ structure
Tertiary Structure• Represented by overall shape of polypeptide• Results from interactions between the side chains of
the Amino Acids• Hydrophobic interaction with van der Waals
interactions– While folding into functional shape, the AA with
hydrophobic (nonpolar) side chains end up clustered together in core of protein
– Caused by water– Van der Waals interactions then hold them together
• This with the hydrogen bonds between polar side chains and ionic bonds help stabilize further
Tertiary Structure• Those with the hydrogen bonds between polar
side chains and ionic bonds help stabilize further
• Reinforced by covalent bonds in disulfide bridges between Two cysteine monomers– Sulfhydryl group of one is brought close to
another with protein folding
3’ Structure
Quaternary Structure
• 2 or more polypeptide chains in one functional macromolecule
• Overall protein structure• Example– Collagen
4’ Structure
Sickle –Cell Anemia
• Slight change in primary structure• Substitution of 1 AA• Blood cells are then sickle-shaped instead of
disk-shaped• Hemoglobin molecules tend to crystallize
Sickle Cell and Oxygen transport
Primarystructure
Secondaryand tertiarystructures
1 2 3
Normal hemoglobinVal His Leu
4Thr
5Pro
6Glu Glu
7Primarystructure
Secondaryand tertiarystructures
1 2 3
Sickle-cell hemoglobinVal His Leu
4Thr
5Pro
6Val Glu
7
Quaternarystructure
Normalhemoglobin(top view)
a
b
b
b
b
a
a
a
Function Molecules donot associatewith oneanother; eachcarries oxygen.
Quaternarystructure
Sickle-cellhemoglobin
Function Molecules interact withone another tocrystallize intoa fiber; capacityto carry oxygenis greatly reduced.
Exposedhydrophobicregionb subunit b subunit
Protein’s Natural Form
What can cause proteins to unravel?
• Changes in natural:– pH– Salt concentration– Temp– Environmental alterations– Changed from an aqueous environment to organic
solvent• Hydrophobic regions face outward
– Disruptions in hydrogen bonds, ionic bonds, and disulfide bridges
– Excessive heat
What is denaturation?
• Biologically inactive• Unraveling• Losing native shape
Denaturation of a protein
Not as simple as it looks
• Intermediate stages exist from primary to quaternary structure
• Chaperonins– Chaperone proteins– Proteins that assist in proper folding of other
proteins– Keep protein from “Bad influences”
Chaperonin
What happens when there is a misfolding?
• Alzheimer’s• Parkinson’s
How do we see the 3D structures?
• X-ray crystallography• Bioinformatics• NMR spectroscopy
What determines the Primary Structure?
• Amino Acid sequence is programmed by gene
What is a gene?
• Unit of inheritance• Consist of DNA
What is DNA?
• A polymer made up of nucleic acids
What is a Nucleic Acid?
• Class of compounds• Enable organisms to reproduce their complex
components from one generation to the next• Two types of nucleic acids exist– Deoxribonucleic acids (DNA)– Ribonucleic acid (RNA)
DNA
• Provides direction for its own replication• Directs RNA synthesis
RNA
• Directs protein synthesis
DNA
• Genetic material organisms inherits from parents
• Each chromosome contains one long DNA molecule– Carries several hundred genes
• Copied and passed from one generation to next when cell reproduces itself by dividing
• Contains the information that programs all the cell’s activities
• Reside in nucleus
DNA
• NOT directly involved in running operations of cell…
• INSTEAD, directs RNA synthesis which directs Protein synthesis
• Protein are required to implement genetic programs and they are the tool for biological functions
RNA
• Each gene along a DNA molecules directs synthesis of type of RNA – called messenger RNA (mRNA)
Messenger RNA
• mRNA• Interacts with cell’s protein-synthesizing
machinery and directs production of polypeptide
DNA -> RNA -> protein
Where does protein synthesis take place in the cell?
• Ribosomes– In cytoplasm in eukaryotic cells
What is a Nucleic Acid?
• Macromolecules that exist as polymers called polynucleotides
What is a polynucleotide?
• Made up of monomers of nucleotides• The strand of nucleotides
What is a nucleotide?
• Three parts:– Nitrogenous base– 5-Carbon Sugar (pentose)– Phosphate group
What is a nucleoside?
• Nucleotide without the phosphate group• Two parts:– Nitrogenous base– 5-Carbon Sugar (pentose)
How to build a nucleotide?
• Two types:– Pyrimidines– Purines
How to build a nucleotide?
• Two families of nitrogenous bases:– Pyrimidines• 6- membered ring of carbon and nitrogen atoms• Examples:
– Cytosine ( C )– Thymine ( T ) – Found only in DNA– Uracil ( U ) – Found only in RNA
How to build a nucleotide?
• Two types:– Pyrimidines– Purines• Larger• 6-membered ring fused to 5-membered ring• Examples:
– Adenine ( A )– Guanine ( G )
How to build a nucleotide?
• The examples differ in chemical groups attached to the rings– Pyrimidines– Purines
Why called nitrogenous bases?
• Nitrogen atoms tend to take up H+ from solution
What is the difference between RNA and DNA?
• Ribose sugar in RNA• consist of a single polynucleotide chain• Deoxyribose sugar in DNA– Lacks oxygen atom on second carbon in the ring
Describing Nucleotide
• Nitrogenous base and sugar both numbered• Sugar atoms have a prime (‘) after the number
to distinguish
How do you build a polynucleotide?• Link nucleotides with phosphodiester linkage– Phosphate group that links the sugars of two
nucleotides• Sugar-phosphate backbone• Two free ends are different• One end has phosphate attached to 5’ carbon– 5’ end
• Other end has hydroxyl group on 3’ carbon– 3’ end
• Built - in directionality -> from 5’ to 3’
Diversity
• From 4 DNA bases and with sequences of bases that are hundred to 1000 bases long, vast arrangement of genes exist
• Linear order of bases in a gene specify amino acid sequence
DNA Double Helix
• DNA molecules have two polynucleotides that spiral around an imaginary axis
• James Watson and Francis Crick 1st proposed the double helix as the 3D structure of DNA in 1953
• Run antiparallel (5’ -> 3’ direction from each other)
• Sugar Phosphate backbone on outside• Nitrogenous bases paired on interior
DNA Double Helix
• Polynucleotides are held together by hydrogen bonds between paired bases
• Polynucleotides are held together by van der Waals interactions between the stacked bases
• Very long• 1000s and millions of bases
How do bases pair?
• A – T• G – C• Sequence of bases along one strand would
give you the sequences of bases along the other strand
• Two strands are complementary• Ex: 5’ – AGGTCCG – 3’
3’ – TCCAGGC – 5’
DNA Replication
• Each of two strands of DNA molecule serves as a template to order nucleotides into a new complementary strand
• Results in two identical copies of the original double-stranded DNA molecule
Tape Measure of Evolution
• Hemoglobin