Biological molecules
The FOUR Classes of Large Biomolecules
• All living things are made up of four classes of
  large biological molecules:
  •   Carbohydrates
  •   Lipids
  •   Protein
  •   Nucleic Acids
• Macromolecules are large molecules composed
  of thousands of covalently bonded atoms
• Molecular structure and function are inseparable
 The FOUR Classes of Large Biomolecules
• Macromolecules are polymers, built
  from monomers
„ A polymer is a long molecule consisting of many
  similar building blocks
„ These small building-block molecules are called
  monomers
„ Three of the four classes of life’s organic
  molecules are polymers
    – Carbohydrates
    – Proteins
    – Nucleic acids
The synthesis and breakdown of polymers
• A dehydration reaction occurs when two monomers
  bond together through the loss of a water molecule
• Polymers are disassembled to monomers by hydrolysis,
  a reaction that is essentially the reverse of the
  dehydration reaction
Dehydration Synthesis
Hydrolysis: Breakdown of polymers
        The Diversity of Polymers
• Each cell has thousands of different macromolecules.
• Macromolecules vary among cells of an organism,
  vary more within a species, and vary even more
  between species.
• An immense variety of polymers can be built from a
  small set of monomers.
     Carbohydrates: serve as Fuel
        and Building Material
• Carbohydrates include sugars and the polymers
  of sugars
• The simplest carbohydrates are monosaccharides,
  or single sugars
• Carbohydrate macromolecules are
  polysaccharides, polymers composed of many
  sugar building blocks
  Breaks down into microscopic
           molecules
Loaf of bread   Bread crumbs       Polysaccharide
 Monosaccharide                Disaccharide
         Sugars: Monosaccharides
• Monosaccharides have molecular            Glucose
  formulas that are usually multiples
  of CH2O
• Glucose (C6H12O6) is the most
  common monosaccharide
• Monosaccharides are classified by
                                         Main “fuel” for
    ‟ The location of the carbonyl group
                                         bacteria, plants
    ‟ The number of carbons in the       and animal cells
      carbon skeleton
13
          Sugars: Disaccharides
• A disaccharide is formed when a dehydration
  reaction joins two monosaccharides
• This covalent bond is called a glycosidic linkage
        Functions of Disaccharides
 Sucrose, for example, is table sugar, and it
  is the most common disaccharide that
  humans eat.
 Lactose is found in breast milk and provides
  nutrition for infants.
 Maltose is a sweetener that is often found in
  chocolates and other candies.
 Since it is an energy storage source, many
  plants such as sugar cane are high in
  sucrose.
Disaccharide
               16
               Polysaccharides
• Polysaccharides, the polymers of sugars, have storage
  and structural roles
• The structure and function of a polysaccharide are
  determined by its sugar monomers and the positions of
  glycosidic linkages
  Types of Polysaccharides: Storage
• Starch, a storage
  polysaccharide of
  plants, consists
  entirely of glucose
  monomers
• Plants store surplus
  starch as granules
  within chloroplasts
  and other plastids
• The simplest form of
  starch is amylose
  Types of Polysaccharides: Storage
• Glycogen is a storage
  polysaccharide in
  animals
• Humans and other
  vertebrates store
  glycogen mainly in
  liver and muscle cells
Types of Polysaccharides: Structural
• The polysaccharide cellulose is a major
  component of the tough wall of plant cells
• Like starch, cellulose is a polymer of glucose, but
  the glycosidic linkages differ
• The difference is based on two ring forms for
  glucose: alpha () and beta ()
Such Elegance!
              Polysaccharide
           Random Acts of Biology
• Cellulose in human food passes through the
  digestive tract as insoluble fiber
• Some microbes use enzymes to digest cellulose
• Many herbivores, from cows to termites, have
  symbiotic relationships with these microbes
• Chitin, another structural polysaccharide, is found
  in the exoskeleton of arthropods (crunch!)
• Chitin also provides structural support for the cell
  walls of many fungi
Use of Cellulose
Source of Chitin
Use of Chitin
            25
Amino acid and Protein
Proteins are polymers of amino acids.
            Facts of Protein
• Proteins are major components of all cellular
  systems
• Proteins consist of one or more linear polymers
  called polypeptides
• Proteins are linear and never branched
• Different AA’s are linked together via PEPTIDE
  bonds
• The individual amino acids within a protein are
  known as RESIDUES
• The smallest known P’ is just nine residues long -
  oxytocin
• The largest is over 25,000 residues - the structural
  protein Titin
                                              Titin
Oxytocin is a peptide hormone          Titin also known as connectin, is
and neuropeptide. It is normally       a protein. Titin is a giant protein,
produced in the hypothalamus           greater than 1 µm in length, that
and released by the posterior          functions as a spring which is
pituitary. It plays a role in social   responsible for the passive elasticity
bonding, reproduction, childbirth,     of muscle.
and the period after childbirth.
This is an amino acid. It is
the monomer for a
protein. It contains C, H,
O and N. It has 3 groups:
an amino group, an R-
group, and a carboxyl
group. The R-group is
considered a variant
group because it
changes.
20 amino acids structure
    Breaks down into microscopic
             molecules
                                Polypeptide
         Meat
                   Amino Acid
Monomer: amino acid
Polymer: polypeptide
                     Proteins
 Elements: C-H-O-N
 Monomer (Building Block):
  amino acids (20 different ones!)
 Polymer: proteins (tons)
 Examples of proteins:
  hemoglobin in red blood cells,
  albumin in eggs, enzymes that
  control reactions in the body,
  and antibodies
 Found in: fish, eggs, meat
Non-covalent bonds within and between Peptide chains
are as important in their overall conformation and
function
                                1) Ionic bonds
                                2) Hydrogen bonds
                                3) Van der Waals forces
The side groups of the linear unfolded polypeptide are
intermingled. Only when correctly folded do we see the
wonder of Nature!
The 3D folding of a P’ is governed solely by the sequence
of the AA’s. Under some physiological conditions & in vitro
many P’s can reversibly unfold and refold
Haemoglobin - is the iron-containing oxygen-transport
metalloprotein in the red blood cells of the blood in vertebrates
and other animals
                                                  Here we see
                                                  the use of two
                                                  different
                                                  polypeptides
                                                  made by
                                                  different genes
Virus Coat Protein
Function of Proteins
   • Provides us with building
     blocks for life!
   • Also regulate most functions
     in a cell.
   • Glycoproteins (antigens)
   • Combines w/DNA to form
     chromosomes
   • Turns genes on and off
   • Antibodies (fights disease)
Function of Proteins
  Provides structure & strength
   (fibers)
  Transports molecules in & out
   cells
  Hemoglobin (transports O2)
  Enzymes (speeds up reactions)-
   has ‟ase suffix..Amylase
  Acts as hormones (insulin)-
   many proteins have suffix of -in
                      Prions
 Prions are misfolded proteins with the ability to transmit
  their misfolded shape onto normal variants of the same
  protein.
 They characterize several fatal and transmissible
  neurodegenerative diseases in humans and many other
  animals.
 Prions cause diseases, but they aren't viruses or bacteria
  or fungi or parasites.
 Abnormal aggregates of proteins called amyloids,
  accumulate in infected tissue and are associated with
  tissue damage and cell death in Alzheimer's
  disease and Parkinson's disease.
Prions
         04_08_Prion diseases.jpg
Lipids and Fats
      Lipids are Hydrophobic
Lipids are a diverse group of hydrophobic
molecules
• Lipids are the one class of large biological
  molecules that do not form polymers
• The unifying feature of lipids is having little or no
  affinity for water (water fearing)
• Lipids are hydrophobic because they consist
  mostly of hydrocarbons, which form nonpolar
  covalent bonds
• The most biologically important lipids are fats,
  phospholipids, and steroids
     Fats: Start with a Simple Little
           Glycerol Molecule
• Fats are constructed from two
  types of smaller molecules:
  glycerol and fatty acids
• 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
Dehydration Reaction 1: Add a Fatty Acid
• Next, add a “fatty acid” through a dehydration
  synthesis reaction
• What makes it an acid? The C double bond O,
  single bond OH!
        Dehydration Reaction 2!!
• Next, add a SECOND “fatty acid” through a
  dehydration synthesis reaction
    Dehydration Reaction THREE!!!
• The joining
  of the C of
  the fatty acid
  to the O of
  the hydroxyl
  group of the
  glycerol is
  called an
  ester
  linkage.
    Saturated or Unsaturated?
• Fats made from
  saturated fatty acids
  are called saturated
  fats, and are solid at
  room temperature
• Most animal fats are
  saturated (lard)
• Saturated fatty acids
  have the maximum
  number of hydrogen
  atoms possible and no
  double bonds
     Saturated or Unsaturated?
• Fats made from
  unsaturated fatty acids are
  called unsaturated fats or
  oils, and are liquid at room
  temperature
• Plant fats and fish fats are
  usually unsaturated
• Unsaturated fatty acids
  have one or more double
  bonds
  Saturated or Unsaturated?
• A diet rich in saturated
  fats may contribute to
  cardiovascular disease
  through plaque deposits
• Hydrogenation is the
  process of converting
  unsaturated fats to
  saturated fats by adding
  hydrogen
        What’s a Trans fat?
• Hydrogenating vegetable oils also creates
  unsaturated fats with trans double bonds
• These trans fats may contribute more than
  saturated fats to cardiovascular disease
     Saturated or Unsaturated?
• Certain unsaturated fatty acids are not synthesized
  in the human body
• These must be supplied in the diet
• These essential fatty acids include the omega-3 (ω-
  3) fatty acids, required for normal growth, and
  thought to provide protection against cardiovascular
  disease
  Fats: Major function is storage!
• The major function of
  fats is energy storage
• Humans and other
  mammals store their
  fat in adipose cells
• Adipose tissue also
  cushions vital organs
  and insulates the
  body
                     Phospholipids
• When phospholipids are added to water, they self-
  assemble into a bilayer, with the hydrophobic tails
  pointing toward the interior
• The structure of phospholipids results in a bilayer
  arrangement found in cell membranes
• Phospholipids are the major component of all cell
  membranes
           Carbohydrate
                                           Phospholipid
                                             bilayer
    Nonpolar
   Hydrophobic
                   Polar
                 Hydrophilic
                          A Single Phospholipid Molecule
                                  Choline
       Hydrophilic head
                                 Phosphate
                                  Glycerol
Hydrophobic tails
                                 Fatty acids
                                                                                 Hydrophilic
                                                                                 head
                                                                                 Hydrophobic
                                                                                 tails
(a) Structural formula                         (b) Space-filling model   (c) Phospholipid symbol
                               Soaps
         Hydrophobic part: nonpolar
        Hydrophilic part: polar (remains in contact with environment)
      O
        -    +
   3 RCO N a
l Sodium soaps
n)
                     Soaps
When soap is mixed with dirt (grease, oil, and …), soap
micelles “dissolve” these nonpolar, water-insoluble
molecules.
                  Steroids
• Steroids are lipids characterized by a carbon
  skeleton consisting of four fused rings
• Cholesterol, an important steroid, is a component
  in animal cell membranes
• Although cholesterol is essential in animals, high
  levels in the blood may contribute to
  cardiovascular disease
                      Sex Hormones
            Progestins (Female Sex Hormones):
The progestin progesterone is called the “pregnancy
hormone”; it is responsible for the preparation of the uterus for
implantation of a fertilized egg.
                    Sex Hormones
Androgens (Male Sex Hormones):
Testosterone and Androsterone are androgens made in the
testes.
They control the development of secondary sex
characteristics in males.
                  Sex Hormones
- Synthetic androgen analogues, called anabolic steroids,
promote muscle growth.
- They have the same effect as testosterone, but are more
stable, so they are not metabolized as quickly.
- They have come to be used by athletes and body builders,
but are not permitted in competitive sports.
- Prolonged use of anabolic steroids can cause physical and
psychological problems.
Nucleic Acids: Information
        Molecules
 The biochemical activity of a cell depends on
  production of a large number of proteins, each
  with a specific sequence.
 The information necessary to produce the correct
  proteins is passed through generations of
  organisms, even though the protein molecules
  themselves are not.
 Nucleic acids carry information inside cells, just as
  disks contain the information in a computer
                                                    65
 Two main varieties of nucleic acids are
  deoxyribonucleic acid (DNA)
  ribonucleic acid (RNA)
 DNA encodes the genetic information used to
  assemble proteins
 Cells use a type of RNA called messenger RNA
  (mRNA) to direct the synthesis of proteins .
 mRNA consists of transcribed single-stranded
  copies of portions of the DNA.
 These transcripts serve as blueprints specifying
  the amino acid sequences of proteins.
Nucleic acids are nucleotide polymers
  Nucleic acids are long polymers of repeating
   subunits called nucleotides.
  Each nucleotide consists of three components:
  A pentose, or five-carbon sugar (ribose in RNA and
   deoxyribose in DNA);
  a phosphate (-PO4 ) group
  an organic nitrogenous (nitrogen-containing) base
                     Nitrogen Bases
• The nitrogen bases in nucleotides consist of two general types:
  - purines: adenine (A) and guanine (G)
  - pyrimidines: cytosine (C), thymine (T) and Uracil (U)
                Pentose Sugars
• There are two related pentose sugars:
  - RNA contains ribose
  - DNA contains deoxyribose
• The sugars have their carbon atoms numbered with
  primes to distinguish them from the nitrogen bases
         Nucleosides and Nucleotides
 A nucleoside consists of a nitrogen base linked by a glycosidic
  bond to C1’ of a ribose or deoxyribose
 Nucleosides are named by changing the nitrogen base ending to
  -osine for purines and –idine for pyrimidines
 A nucleotide is a nucleoside that forms a phosphate ester with
  the C5’ OH group of ribose or deoxyribose
 Nucleotides are named using the name of the nucleoside
  followed by 5’-monophosphate
Names of Nucleosides and
      Nucleotides
      Primary Structure of Nucleic Acids
 The primary structure of a nucleic acid is the nucleotide sequence
 The nucleotides in nucleic acids are joined by phosphodiester bonds
 The 3’-OH group of the sugar in one nucleotide forms an ester bond
  to the phosphate group on the 5’-carbon of the sugar of the next
  nucleotide
            Reading Primary Structure
 A nucleic acid polymer has a free 5’-
  phosphate group at one end and a
  free 3’-OH group at the other end
 The sequence is read from the free
  5’-end using the letters of the bases
 This example reads
       5’—A—C—G—T—3’
75
   Secondary Structure: DNA Double Helix
• In DNA there are two strands of nucleotides that wind together
  in a double helix
  - the strands run in opposite directions
  - the bases are arranged in step-like pairs
  - the base pairs are held together by hydrogen bonding
• The pairing of the bases from the two strands is very specific
• The complimentary base pairs are A-T and G-C
  - two hydrogen bonds form between A and T
  - three hydrogen bonds form between G and C
• Each pair consists of a purine and a pyrimidine, so they are the
  same width, keeping the two strands at equal distances from
  each other
Eukaryotic Nuclear DNA organization
• Nucleosome: DNA
  associated with histone
  protein
• Chromatin: collection of
  nucleosome and linker
  DNA
• Chromosome: condensed
  chromatin
   – Ends of chromosomes
     are called telomeres
     (very repetitive
     sequences)
Nobody can pack as
nature has packed:
DNA Condensation
If you were to take one
molecule of DNA from a
human cell and stretch it
out to its full length, it
would be approximately
two meters long. So it is
truly incredible that such an
enormously long molecule
can be compressed into
the microscopic space of
the nucleus of a cell.
       Unpacking of DNA as a fraction of time (femto seconds)
       and space (1014 cells) is a far far bigger challenge
Next Lecture:
Central Dogma of Molecular Biology