The Macromolecules of the Cell

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The Macromolecules of the Cell

• Chapter 3
• The World of the Cell

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But First, What You Missed in Chapter 1

• The Cell Theory
• The Emergence of Modern Cell Biology
• Light microscopy
• Phase-contrast and D.I.C. microscopy
• Electron microscopy
• Biochemistry and genetics
• The Scientific Method

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But Wait! Theres More (Chapter 2)

• The importance of Carbon
• The Importance of Water
• The Importance of Selectively Permeable Membranes
• The Importance of Synthesis by Polymerization
• The Importance of Self-Assembly

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And Now Chapter 3

• Proteins
• Nucleic Acids
• Polysaccharides
• Lipids

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30 Most Common Monomers in Cells
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Proteins

• Based on function, proteins fall into 4 major
  classes
• Enzymes biological catalysts
• Structural proteins provide support and shape
• Motility proteins provide cell ability to move
• Regulatory proteins control and coordination of
  cellular function
• Monofunctional or bifunctional roles

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Proteins

• Linear polymers of amino acids
• gt60 kinds in a cell, but only 20 involved in
  protein synthesis
• The 20 essential amino acids categorized into
  three groups
• Non-polar (hydrophobic)
• Polar uncharged (hydrophilic)
• Polar charged (hydrophilic)

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Proteins

• Every amino acid has a similar basic structure
• NH3CHRCOOH
• Except for glycine (R H), all amino acids have
  at least one asymmetric carbon atom and exists as
  two stereoisomers (D or L)
• Only L form exists in proteins

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Proteins

• Proteins are built through a series of
  dehydration (a.k.a. condensation) reactions
• The H and OH groups are removed from the carboxyl
  group of one amino acid and the amino group from
  the next amino acid
• The removal of water forms a covalent amide
  (a.k.a. peptide) bond

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Proteins

• By forming peptide bonds, the orientation of the
  amino acids create an amino terminus and carboxyl
  terminus
• The process of protein synthesis must require
  both energy and information
• Energy required for amino acid activation and
  incorporation onto a tRNA
• Information is needed to determine the order of
  incorporation of amino acids and is determined by
  mRNA

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Proteins

• Peptide a short chain of amino acids
• Polypeptide a long chain of amino acids
• May be a functional monomeric protein
• Multimeric protein consists of two or more
  polypeptide subunits
• Homodimer consists of 2 identical subunits
• Heterodimer consists of 2 different subunits
  (usually designated a and b)
• Heterotrimer consists of 3 different subunits
  (usually designated a, b and g)

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Proteins

• Organization levels determining protein structure

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Proteins

• Primary structure
• Important genetically
• Important structurally by introducing the proper
  sequence of amino acids that will provide for
  appropriate folding of the protein
• A single substitution may result in a protein
  that is not folded properly (hemoglobin)

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Primary Structure

• Written from amino terminus to carboxyl terminus
• Coded for by nucleotide sequence from the mRNA,
  therefore represents the commands of the DNA
  sequence
• Sequence determines secondary, tertiary and
  quaternary structures, as well as protein-protein
  and protein-nucleic acid recognitions

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Proteins

• Secondary structure
• Involves local interactions between amino acids
• Interactions lead to the formation of the a helix
  or b sheet
• Helix is derived from repeating polymers and
  results in 3.6 amino acids per turn, bringing
  every 4th amino acid in proximity
• L, M, and E are strong helix formers
• G and P are helix breakers and are involved in
  bends and turns in helices
• This results in the formation of a hydrogen bond
  between the imino of one residue and the carbonyl
  of another residue

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Proteins

• The b sheet
• Maximized by hydrogen bonding, but between two
  polypeptides or two different segments of one
  polypeptide
• I, V, and F are strong sheet formers
• If the two strands linked are aligned with both
  amino and both carbonyl groups running in the
  same direction, then this is a parallel sheet
• If the two strands run in opposite directions,
  this is an anti-parallel sheet

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Proteins

• Motifs commonly occurring secondary structures
• b-a-b motif
• Hairpin turn motif
• Helix-turn-helix motif

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Proteins

• Tertiary structure
• depends more on the R groups than the imino or
  carbonyl groups
• Hydrophobic domains tend to associate with one
  another and are often found in the inner
  sanctions of the protein
• Hydrophobic and hydrophilic domains impart the
  native conformation, which can occur
  spontaneously or through the use of chaperones

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Proteins

• Stabilization of tertiary structures
• Noncovalent bonds
• Hydrogen bonds between appropriate R groups
• Electrostatic interactions between charged R
  groups
• Hydrophobic interactions between nonpolar R
  groups
• Covalent bonds
• Disulfide bond between two cysteine residues
• Disulfide bonds are important for stabilizing
  both tertiary and quaternary structures

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Proteins

• Fibrous
• Have extensive secondary structure, with
  extremely long stretches of helix or sheet
  structure
• Fibroin, keratin, collagen, elastin
• Globular
• Most proteins involved in cellular structure
• Helices and sheets are present, and permit
  further folding of the protein

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Proteins

• Most globular proteins consists of several
  domains
• A domain is a discrete, locally folded unit of
  tertiary structure
• 50-350 residues
• Each domain has a specific function within the
  protein
• Metal binding domain of enzymes

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Proteins

• Domains
• Small globular proteins tend to have a single
  domain
• Large globular proteins have multiple domains

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Globular proteins with single domains
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Glyceraldehyde phosphate dehydrogenase two
functional domains
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Proteins

• Quaternary Structure
• Level of organization related to subunit
  interactions and assemblies
• Integrins (extracellular matrix receptors)
  contain a and b subunits

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Alpha 2 beta 1 integrin domain 1
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IgG Fab
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Nucleic Acids

• Store, carry, and aid in the transmission of
  genetic information
• Linear polymers of nucleotides
• Differ in type of sugar used and length of
  polymers
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)
• Sugar in each case is the pentose ribose

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Nucleic acids

• Deoxyribonucleic acid
• 2 hydroxyl group of ribose is replaced by
  hydrogen
• Four nucleotide bases (ATCG)
• Phosphate group
• Ribonucleic acid
• Ribose
• Four nucleotide bases (AUCG)
• Phosphate

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RNA
1base sugar 2base sugar phosphate
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DNA
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Polymers

• Linear polymers formed through phosphodiester
  linkage
• Phosphate is attached by phosphoester bond to 5
  carbon of a nucleotide or deoxynucleotide
• Forms bond with 3 carbon of next
  nucleotide/deoxynucleotide
• Forms 3, 5 phosphodiester bond
• Requires energy input supplied by a nucleotide
  triphosphate

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Nucleic Acids

• Recognition of molecules depends on features of
  purines and pyrimidines
• Carbonyl groups and nitrogen are capable of
  hydrogen bonding
• Hydrogen bonds form between AT or AU or between
  GC

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DNA

• DNA is the basic hereditary material in all cells
  and contains all the information necessary to
  make proteins
• DNA is a linear polymer that is made up of
  nucleotide units. The nucleotide unit consists of
  a base, a deoxyribose sugar, and a phosphate.
  There are four types of bases adenine (A),
  thymine (T), guanine (G), and cytosine (C). Each
  base is connected to a sugar via a ß glycosyl
  linkage. The nucleotide units are connected via
  the O3' and O5' atoms forming phosphodiester
  linkages

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DNA

• The results of fiber and single crystal x-ray
  crystallographic studies have shown that DNA can
  have several conformations. The most common one
  is called B-DNA. B-DNA is a right-handed double
  helix with a wide and narrow groove. The bases
  are perpendicular to the helix axis.

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DNA

• DNA can also be found in the A form in which the
  major groove is very deep and the minor groove is
  quite shallow.
• A very unusual form of DNA is the left-handed
  Z-DNA. In this DNA, the basic building block
  consists of two nucleotides, each with different
  conformations. Z-DNA forms excellent crystals.

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RNA

• RNA is a polymer that contains ribose rather than
  deoxyribose sugars. The normal base composition
  is made up of guanine, adenine, cytosine, and
  uracil
• RNA can form double stranded duplexes. These
  duplexes are in the A conformation because the
  2'OH precludes the B conformation. More commonly,
  RNA is single stranded and can form complex and
  unusual shapes.

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RNA

• Examples of RNA structures include tRNA, which is
  the key molecule involved in the translation of
  genetic information to proteins. tRNA contains
  about 70 bases that are folded such that there
  are base paired stems and open loops. The overall
  shape of the completely folded tRNA is L shaped.

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A-RNA
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Double stranded RNA
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tRNA
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Carbohydrates

• Monosaccharides - simple sugars with multiple OH
  groups. Based on number of carbons (3, 4, 5, 6),
  a monosaccharide is a triose, tetrose, pentose or
  hexose.
• Disaccharides - 2 monosaccharides covalently
  linked.
• Oligosaccharides - a few monosaccharides
  covalently linked.
• Polysaccharides - polymers consisting of chains
  of monosaccharide or disaccharide units.

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Monosaccharides

• Aldoses (e.g., glucose) have an aldehyde group at
  one end.

Ketoses (e.g., fructose) have a keto group,
usually at C2.
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D vs. L Designation

• D L designations are based on the configuration
  about the single asymmetric C in glyceraldehyde.
• The lower representations are Fischer Projections.

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D and L sugars

• For sugars with more than one chiral center, D or
  L refers to the asymmetric C farthest from the
  aldehyde or keto group.
• Most naturally occurring sugars are D isomers.

D and L sugars are mirror images of one another.
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Sugar nomenclature

• D L sugars (mirror images of one another) have
  the same name, e.g., D-glucose L-glucose.
• Other stereoisomers have unique names.
• The number of stereoisomers is 2n, where n is the
  number of asymmetric centers.
• The 6-C aldoses have 4 asymmetric centers. Thus
  there are 16 stereoisomers (8 D-sugars and 8
  L-sugars).

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Hemiacetal hemiketal formation

• An aldehyde can react with an alcohol to form a
  hemiacetal.
• A ketone can react with an alcohol to form a
  hemiketal.

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• Pentoses and hexoses can cyclize as the ketone or
  aldehyde reacts with a distal OH.
• Glucose forms an intramolecular hemiacetal, as
  the C1 aldehyde C5 OH react, to form a
  6-member pyranose ring, named after pyran.

The representations of the cyclic sugars above
are called Haworth projections.
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• Cyclization of glucose produces a new asymmetric
  center at C1. The 2 stereoisomers are called
  anomers, a b.
• Haworth projections represent the cyclic sugars
  as having essentially planar rings, with the OH
  at the anomeric C1
• a (OH below the ring)
• b (OH above the ring).

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Glycosidic Bonds

• The anomeric hydroxyl and a hydroxyl of another
  sugar or some other compound can join together,
  splitting out water to form a glycosidic bond
• R-OH HO-R' ? R-O-R' H2O
• E.g., methanol reacts with an OH on glucose to
  form methyl glucoside.

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Disaccharides Maltose, a cleavage product of
starch, is a disaccharide with an a(1?4)
glycosidic link between the C1 OH C4 OH of 2
glucoses. It is the a anomer, because the O on C1
points down.

• Cellobiose, a product of cellulose breakdown, is
  the otherwise equivalent b anomer (O on C1 points
  up). The b(1?4) glycosidic linkage is represented
  as a zigzag, but one glucose is actually flipped
  over relative to the other.

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Disaccharides

• Other common disaccharides include
• Sucrose, common table sugar, has a glycosidic
  bond linking the anomeric hydroxyls of glucose
  fructose.
• Because the configuration at the anomeric C of
  glucose is a (O points down from ring), the
  linkage is a(1?2).
• The full name of sucrose is
  a-D-glucopyranosyl-(1?2)-b-D-fructopyranose.)
• Lactose, milk sugar, is composed of galactose
  glucose, with b(1?4) linkage from the anomeric OH
  of galactose. Its full name is b-D-galactopyranosy
  l- (1?4)-a-D-glucopyranose

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Glucose Storage in Plants

• Plants store glucose as amylose or amylopectin,
  glucose polymers collectively called starch.
  Glucose storage in polymeric form minimizes
  osmotic effects.
• Amylose is a glucose polymer with a(1?4)
  linkages.
• The end of the polysaccharide with an anomeric C1
  not involved in a glycosidic bond is called the
  reducing end.
• Amylose adopts a helical conformation.

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• Amylopectin is a glucose polymer with mainly
  a(1?4) linkages, but it also has branches formed
  by a(1?6) linkages. Branches are generally longer
  than shown above.
• The branches produce a compact structure
  provide multiple chain ends at which enzymatic
  cleavage can occur.

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• Glycogen, the glucose storage polymer in animals,
  is similar in structure to amylopectin. But
  glycogen has more a(1?6) branches.
• The highly branched structure permits rapid
  release of glucose from glycogen stores, e.g., in
  muscle during exercise. The ability to rapidly
  mobilize glucose is more essential to animals
  than to plants.

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• Cellulose, a major constituent of plant cell
  walls, consists of long linear chains of glucose
  with b(1?4) linkages.
• Every other glucose is flipped over, due to the b
  linkages. This promotes intrachain interchain
  H-bonds, as well as van der Waals interactions,
  that cause cellulose chains to be straight and
  interact laterally in thick, strong bundles.
• The role of cellulose is to impart strength and
  rigidity to plant cell walls. Assemblies of
  Cellulose Synthase enzymes in the plasma membrane
  spin out bundles of parallel cellulose chains
  from the plant cell surface.

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Oligosaccharides of glycoproteins glycolipids
may be linear or branched chains. They often
include modified sugars (e.g., acetylglucosamine).
O-linked oligosaccharides of glycoproteins may
be relatively simple, with a glycosidic bond from
one sugar to a Ser or Thr OH.

• N-linked oligosaccharides of glycoproteins are
  complex branched chains, linked to an Asn residue
  in a particular 3-amino acid sequence.

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Lipids
Lipids are non-polar (hydrophobic) compounds,
soluble in organic solvents. Most membrane
lipids are amphipathic, having a non-polar end
and a polar end. Fatty acids, the simplest
lipids, consist of a hydrocarbon chain with a
carboxylic acid at one end. an 16-C fatty acid
CH3(CH2)14-COO- Non-polar
polar
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Abbreviated notation for a 16-C fatty acid with
one cis double bond between carbons 9 10 is 161
cis D9. Some examples

• 140  myristic acid
• 160  palmitic acid
• 180  stearic acid
• 181 cisD9  oleic acid
• 182 cisD9,12  linoleic acid
• 183 cisD9,12,15  a-linonenic acid
• 204 cisD5,8,11,14  arachidonic acid
• 205 cisD5,8,11,14,17  eicosapentaenoic acid

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Double bonds in fatty acids are usually have the
cis configuration.

• Most naturally occurring fatty acids have an even
  number of carbon atoms.
• There is free rotation about C-C bonds in a fatty
  acid, except at a double bond. Each cis double
  bond causes a kink in the chain. Rotation about
  other C-C bonds would permit a more linear
  structure than shown above, but with a kink.

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Glycerophospholipids

• Glycerophospholipids (phosphoglycerides), are
  common constituents of cellular membranes. They
  have a glycerol backbone.
• Hydroxyls at C1 C2 are esterified to fatty
  acids.

An ester forms when a hydroxyl reacts with a
carboxylic acid, with loss of H2O.
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• In most glycerophospholipids (phosphoglycerides),
  Pi is in turn esterified to OH of a polar head
  group (X), e.g.
• serine, choline, ethanolamine, glycerol, or
  inositol.
• The 2 fatty acids tend to be non-identical. They
  may differ in length and/or the presence/absence
  of double bonds.

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• Phosphatidylcholine, with choline as polar head
  group, is an example of a glycerophospholipid. It
  is a common membrane lipid.

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• Phosphatidylinositol, with inositol as polar head
  group, is another example of a glycerophospholipid
  .
• In addition to being a membrane lipid,
  phosphatidyl inositol has roles in cell signaling.

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Glycerophospholipid

• Each glycerophospholipid includes
• a polar region glycerol, carbonyl of fatty
  acids, Pi, polar head group (X)
• 2 non-polar hydrocarbon tails of fatty acids (R1,
  R2).
• Such an amphipathic lipid
• is often represented as at right.

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Sphingolipids are derivatives of the lipid
sphingosine, which has a long hydrocarbon tail,
and a polar domain that includes an amino group.

• The amino group of sphingosine can form an amide
  bond with a fatty acid carboxyl to yield a
  ceramide.
• Ceramides usually include a polar head group,
  esterified to the terminal OH of the sphingosine.

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Sphingomyelin, a ceramide with a phosphocholine
or phosphethanolamine head group, is a common
constituent of plasma membranes
Sphingomyelin, with a phosphocholine head group,
is similar in size and shape to the
glycerophospholipid phosphatidyl choline.
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Polar head groups of sphingolipids (ceramides)
Gangliosides, which have complex oligosaccharide
head groups, are often found in the outer leaflet
of the plasma membrane bilayer, with sugar chains
extending out from the cell surface.
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Cholesterol

• Cholesterol has a rigid ring system and a short
  branched hydrocarbon tail. It is largely
  hydrophobic, but has one polar group, a hydroxyl,
  making it amphipathic.
• Cholesterol is found in membranes, and is the
  precursor for synthesis of steroid hormones and
  vitamin D.