A Cellular World
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`Page 1 of21
`
`A Cellular World
`PH709 The Biology of Public Health
`
`PH709 A Cellular World
`
`The Building Blocks of Life
`
`This is a video segment (3:36) from Discovery Channel. it's a very basic introduction to cells, but may be of interest
`to students with little background in the sciences.
`
`Learning Objectives
`
`After successfully completing this section, the student will be able to:
`
`List and distinguish the major organic molecules (sugars and starches; amino acids and proteins, nucleotides
`and nucleic acids; fatty acids, phospholipids, trigylcerides, and cholesterol) and explain how polymers provide
`for increasingly complex molecules.
`Distinguish between covalent and ionic chemical bonds.
`Explain what is meant by a “polar" compound.
`Explain how the amphipathic nature of molecules enables the self-assembly of macromolecular structures
`such as the cell membrane.
`
`Describe the composition of the cell membrane.
`List the functions of protein molecules in cells. Define what is meant by "protein binding sites".
`Describe the three mechanisms by which proteins enable transport of substances across cell membranes.
`List and distinguish the hierarchy of organization within organisms (atoms —> molecules -> organelles -> cells
`-> tissues -> organs ~> organ systems)
`
`Beaten university Echool at Pubtic Heaith
`
`Chemical Elements: Atoms
`
`All matter,
`whether it is
`
`living or not,
`IS
`
`‘
`
`composed
`of chemical
`
`
`
`Textron Exhibit 1001 pg. 1
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Ccl1ular_World/PI-I709_A_Cellular_. ..
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`9/30/2013
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`

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`A Cellular World
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`Page 2 of 21
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`elements;
`these are fundamental chemicals in the sense that they are what they are — they can't be changed into another
`element. Each element is distinguished by the number of protons, neutrons, and electrons that it possess. For
`example, carbon's atomic number is 6, and has an atomic mass of about 12, because it has 6 positively charged
`protons and 6 non-charged neutrons. The 6 charged electrons contribute very little to the atomic mass. There are
`92 natura|ly—occurring elements on earth. The array of elements and their subatomic structure are summarized by
`the periodic table of the elements, shown to the right.
`
`In living organisms the most abundant elements are carbon, hydrogen, and oxygen. These three elements along
`with nitrogen, phosphorus, and a handful of other elements account for the vast majority of living matter. An atom is
`one single unit of a chemical element. Some of these elements that are abundant in organic molecules are shown
`below.
`
` Hydrogen /_,\
`
`\‘\
`
`_’ p Owns
`.
`eutrons
`
`/
`1 electron
`
`1 proton
`
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`
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`
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`
`Molecules
`
`Atoms can combine with other
`atoms by forming chemical bonds.
`
`Covalent Bonds
`
`A covalent bond is one in which
`one or more pairs of electrons are
`shared by two atoms. The
`illustration to the right shows two
`atoms of oxygen that are covalently
`bonded by the sharing of two pairs
`of electrons as illustrated in the shaded area.
`
`Vie;
`
`
`E <
`
`.......‘
`
`Oxygen gas (02)
`
`0:0
`
`A double covalent bond
`(sharing 2 pairs of electrons)
`
`\~—~
`
`The figure below shows a series of molecules formed by covalent binding. Mouse over each molecule to see a brief
`description.
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Cellular_Wor1d/PH709_A_Cellular_. ..
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`9/3 0/2013
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`Textron Exhlblt 1001 pg. 2
`
`

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`A Cellular World
`
`Page 3 of 21
`
`Water is a Polar Molecule
`
`Note also that the sharing of electrons is not always equal. For example, in a water
`molecule, the negatively charged electrons spend more time in the vicinity of the
`heavier oxygen atom. The net result is that the water molecule has one end that is
`more negative relative to the other end. Water is therefore a "polar" molecule. We
`will see that this polarity has important implications for many biological phenomena
`including cell structure. You may have heard the expression "/ike dissolves like."
`What this means is that polar molecules dissolve well in polar fluids like water.
`Sugars (e.g., glucose) and salts are polar molecules, and they dissolve in water,
`because the positive and negative parts of the two types of molecules can distribute
`themselves comfortably among one another.
`
`
`
`‘Test ircuraetli
`
`Q.
`
`Ionic Bonds
`
`Sodium has a single electron in its outermost orbital shell, and it is thermodynamically more stable if it gives up this
`electron. This loss ofa negative electron results in a positively charged sodium ion, abbreviated Na+. Chlorine, on
`the other hand, has seven electrons in its outermost orbital shell, and it is more thermodynamically stable if it
`acquires an extra electron to complete the outer orbital shell. This results in a negatively charged chloride ion,
`abbreviated Na+. The positively charged sodium ions and the negatively charged chloride ions attract each other
`and result in the formation of an ionic bond. In the absence of water, sodium and chloride form a crystal lattice
`because of the attraction of negative and positive ions.
`
`Crystal Lattice of NaCl (table salt)
`
`
`
`However, if sodium chloride crystals are placed in water, the polar water molecules will "hydrate" the sodium and
`chloride atoms because the water molecules are polar. In the illustration below the darker blue V-shaped figures
`represent water molecules, which are polar. The positive ends of the water molecules are attracted to the negatively
`charged chloride ions, while the negative pole of the water molecule is attracted to the positive sodium ions. As a
`result, the ions are hydrated and the crystal lattice dissolves into the aqueous solution. This is exactly what happens
`when you add crystalline table salt to a glass of water.
`
`http1//sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Cellular_World/PH709_A__Cellular_...
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`9/30/2013
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`Textron Exhibit 1001 pg. 3
`
`

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`A Cellular World
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`Page 4 of21
`
`
`
`The video below provides an animated explanation of how salts like NaC| dissolve in water.
`
`More Complex Biological Molecules
`
`Carbohydrates
`
`Sugar Molecules
`
`The stuff of life is amazingly diverse and complex, but it is all based on combinations of simple biological molecules.
`Biological molecules are often made from chains & rings of carbon. These molecular structures can be represented
`by "stick drawings" that show the component atoms (e.g., C, H, N, O for carbon, hydrogen, nitrogen, and oxygen
`respectively) and show the bonds between them as dashes. A single dash ( —) represents a single bond, and a
`double dash (=) represents a double bond.
`
`I
`H '— C """ H
`I
`
`Note that some common "groups" are depicted
`without showing the bonds between them. For
`example, the hydroxyl group (—OH) in the sugar
`molecule below is an oxygen bonded to a
`hydrogen, as show more explicitly to the left. The
`"Cl-l2OH" group at the bottom of the glucose
`molecule shown below is a shorthand notation for
`the structure shown more explicitly to the right.‘
`
`/ O
`
`--H
`
`For example, a molecule of the sugar glucose consists of 6
`carbon atoms bonded together as a chain with additional
`atoms of oxygen and hydrogen. This short chain forms a ring
`in aqueous solutions, e.g., in body fluids, as shown to the
`right.
`
`s
`
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`D-glucose
`
`Fructose is another sugar, which also has 6 carbons, 12 hydrogens, and 6 oxygen atoms. However, the
`
`http://sph.bu.edu/otlt/MPH-Modules/PI-I/PH709_A__Ce1lular_World/PH709_A_Ce1lular_...
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`9/30/2013
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`Textron Exhlbli 1001 pg. 4
`
`

`
`A Cellular World
`
`_
`
`Page 5 of 21
`
`arrangement of the atoms is different, and this makes it much sweeter than glucose and also affects its ability to
`combine with other molecules.
`
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`
`Another important theme is that single units of biological molecules
`(monomers) can join to form increasingly complex molecules (polymers).
`For example, two monosaccharide sugars can also become bound
`together chemically to form a disaccharide. Sucrose is the disaccharide in
`common sugar that we buy at the grocery store. The structure of sucrose
`is shown at the right.
`
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`Poiysaccharides: Starch, Glycogen, and Cellulose
`
`Glucose and fructose are examples of monosaccharides, meaning they consist of a single sugar unit, while sucrose
`is an example of a disaccharide. However, sugar units can be bonded or linked together to form polysaccharides,
`which consist of many sugars linked together to form extensive chains of sugars. Plants store energy as starch,
`which consists of very long chains of glucose linked together. Animals store energy as glycogen, which consists of
`more highly branched chains of glucose. Collectively, sugars, starch, and glycogen are know as carbohydrates, and
`they are an important source of cellular energy.
`
`«
`
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`
`l»l'C1Dl*l
`
`Cellulose is yet another poiysaccharide formed from glucose.‘ Cellulose is composed of unbranched, parallel chains
`of glucose. A key feature is that the chains bond to one another to form strong fibers that serve a structural purpose.
`Humans do not have the enzymes necessary to break the bonds in cellulose, and any cellulose we ingest passes
`through our digestive systems. it is a major component of what we refer to as distant "fiber."
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Cellular_W0rld/PH709_A_Cellular_...
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`9/30/2013
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`Textron Exhibit 1001 pg. 5
`
`

`
`A Cellular World
`
`i
`
`Page 6 of 21
`
`Cellulose
`
`%
`
`CHzOH
`
`CH_2OH
`
` /am-lwcngou
`
`
`
`cnzon
`
`From http://nlko.unl.edu/bs'l 01/pix/ce||ulose.gif
`
`Cellulose fibers,
`
`From http://www.jpk.com/cellulose.110.en.html
`
`Lipids
`
`Lipids are a family of compounds whose diversity is also made possible by building complex molecules from
`multiple units of simpler molecules, and once again one sees characteristic rings and chains.
`
`Polar and Non-polar Molecules
`
`You are. of course, aware of the expression "oil and water don't mix," and you have all observed how salad
`dressing composed of vinegar (which is aqueous, i.e., largely water) and oil will separate when left to stand. The
`positive ends of the water molecule are attracted to the negative ends of adjacent water molecules, as shown in the
`figure below, and this enables water molecules to coalesce. You may have also seen water bead on a car
`windshield as a result of this phenomenon.
`
`
`
`Many lipids, on the other hand, are non-polar, meaning that the charge distribution is evenly distributed. Non-polar
`molecules do not dissolve well in water; in fact, polar and non~polar molecules tend to repel each other in the same
`way that oil and water don't mix and will separate from each other even if they are shaken vigorously in an attempt
`to mix them.
`
`This distinction between polar-and non-polar molecules has important consequences for living things, which are
`composed of both polar molecules and non-polar molecules. The next sections will illustrate the importance of this.
`
`Fatty Acids
`
`..........-x~~»-w-vm
`
`l...,..................m»»««~»~s
`
`.,
`
`Textron Exhibit 1001 pg. 6
`
`http://sph.bu.edu/otlt/MPH—Modules/PH/PH709__A_Ce1lular_World/PH709_A_Cellular_...
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`9/30/2013
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`

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`A Cellular World
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`Page 7 of 21
`
`Fatty acids are chain—like molecules that are important components of several types of lipids. The illustrations below
`show two different fatty acid molecules. Each has a characteristic carboxyl group (the -COOH) attached to a chain
`of carbons with hydrogen atoms attached to the carbon chain. Two things are noteworthy. First, the hydrocarbon
`chain is very non-polar and therefore doesn't dissolve in water very well. However, hydrocarbon chains do associate
`with each other readily. Second, note that the unsaturated fatty acid has two hydrogens removed. and this allows
`formation of a double bond, i.e., a stronger bond between two of the carbon atoms. Note also that the double bond
`tends to produce a bend or a kink in the fatty acid. The illustration to the right shows two other common fatty acids:
`stearic acid, which is a straight 18 carbon chain with no double bonds. and oleic acid, which is an 18 carbon chain
`with a single double bond, which cause a bend.
`
`Triglycerides
`
`A fat molecule is a type of lipid that
`consists of three fatty acid molecules
`connected to a 3 carbon glycerol
`backbone‘, as shown on the right. The three
`fatty acids can be different from one
`another. Since the hydrocarbon chains are
`very non-polar, fats do no dissolve in water;
`instead, fat molecules tend to coalesce with
`one another. Since a fat molecule has 3
`fatty acids connected to a glycerol
`
`molecule, they are also called trlgylcerides.
`
`Phospholipids
`
`
`
`Phospholipids constitute another important
`class of lipids. These are similar to similar
`to trlgylcerides in that they have a glycerol
`backbone, but there are only two fatty acids
`connected to glycerol. The third carbon of
`the glycerol backbone is attached to a
`phosphate group (an atom of phosphorus
`bonded to four atoms of oxygen), and the
`phosphate group is attached to a base
`molecule of choline, serine, or
`ethanolamine.
`
`The part of the phospholipid with
`phosphate and the base is actually very
`polar, and it tends to rotate away from the
`two fatty acids. This makes phospholipid
`molecules have a hairpin shape. The head of the hairpin is very polar and therefore likes to associate with water (it
`is hydrophilic), while the two fatty acid chains (the "talls") are very non-polar and tend to avoid water (hydrophobic)
`and associate with other hydrocarbon chains.
`
`Phospholipids can be described as amphipathic ("amphi" means "both“), because they have this dual nature (part
`polar and part non-polar). This characteristic causes phospholipids to self—associate into large macromolecular
`complexes in an aqueous (watery) environment.
`
`Cholesterol
`
`("Ho ("Hrs
`
`(‘He (He
`
`Cholesterol is also an important component of animal
`'
`
`Textron Exhibit 1001 pg. 7
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Ce1lular_World/PH709_A_Cellular_...
`
`9/3 0/2013
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`

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`A Cellular World
`
`Page 8 of 21
`
`membranes (plant membranes have a similar, but distinct
`'stero|' in their membranes). it is a lipid, because it is composed almost entirely of carbon and hydrogen, but it is
`different from fatty acids, fats and phospholipids in that it is arranged in a series of rings. The rings consist of 5 or 6
`carbon atoms bonded together. The carbon atoms at the apices of the hexagonal and pentagonal rings have
`hydrogen atoms attached to them. The ring~like structures are fairly rigid, but there is also a hydrocarbon tail, which
`is somewhat flexible. The entire structure is somewhat reminiscent of a fancy kits with a tail.
`
`Cholesterol is very non-polar, except for the hydroxyl group attached to the first ring. Consequently, in an animal
`cell membrane the polar hydroxyl group sticks into the aqueous environment (either extracellular water or
`intracellular water), and the rest of the cholesterol molecule, which is non-polar, is found among the non-polar fatty
`acid tails of the phospholipids.The image below depicts a section of a cell membrane with water outside and inside.
`The polar headgroups of the phospholipids are represented in red, and their non-polar fatty acid tails are shown as
`zig—zag lines extending from the polar head group. As we we see in greater detail, cell membranes consist of a
`bilayer of phospholipids with other molecules inserted into the bilayer. This illustration shows five cholesterol
`molecules (the black structures with four conjoined rings) inserted into the lipid bilayer. Most of the cholesterol
`molecule in non-polar and therefore associations with the non-polar fatty acid tails of the phospholipids. However,
`the hydroxyl group (—OH) on cholesterol carries a negative charge and therefore associates with the polar
`environment of water either inside the cell or outside.
`
`
`
`Overview of Cell Structure and Function
`
`
`
`Non-polar
`fatty acid tails
`
`: pathic" = Dual nature
`
`~/vvvx/v\/\
`
`The Cell Membrane - A Fluid Mosaic of Molecules
`
`If you were to add small amounts of phospholipid
`molecules to water, they will align so that the polar
`head groups are in the water, and the non-polar
`fatty acid tails will stick up from the surface of the
`water and form an oily film. If you were to continue
`to add phospholipids, the film would eventually
`cover the entire surface.
`
`Polar head
`group
`
`
`
`Textron Exhibit 1001 pg. 8
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A_Cellular_World/PH709_A_Cellular_...
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`9/30/2013
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`

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`A Cellular World
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`Page 9 of 21
`
`
`
`Oily Layer
`
`Once the surface of the water becomes completely
`saturated with phospholipid, addition of still more
`phospholipid would result in formation of a bilayer
`within the water (as shown on the left). since this
`would be the most thermodynamically stable
`structure, allowing all of the polar heads of the
`phospholipids to be in contact with water, while at
`the same time allowing all of the non—po|ar fatty
`acid tails to be sheltered amongst themselves in an
`oily layer that is away from the water.
`
`With the addition of even more phospholipid to this
`aqueous solution the phospholipids would spontaneously form spherical bilayers of phospholipids that had water
`inside and outside as depicted in the figure below to the right.
`-
`
`This bilayer structure is actually the basic structure for cell membranes and
`many of the internal structures (organelles) within cells. Imagine a cell as a
`three dimensional sac consisting of a bilayer of phospholipid molecules.
`There is water inside the cell and outside the cell, and the polar heads of
`the phospholipids protrude into the water (shown in blue). Certainly the
`structure of cells is far more complex than this. Cell membranes have
`many proteins and glycoproteins which serve many functions,, e.g. as
`signal receptors and transport conduits to move molecules in and out of
`the cell. The video below gives a sense ofthe structure and function of the
`
`"plasma membrane."
`
`Test Yourself
`
`The Flash animation below gives further detail about the functions of some of the membrane's proteins. Click on the
`name of each protein type to see more detailed information. [This Flash animation is from "Biology ~ The Unity and
`Diversity of Life", 9th edition, by Cecie Starr and Ralph Taggart, Brooks/Cole - Thomson Learning, 2001 .]
`
`Nucleic Acids
`
`There are two types of
`nucleic acids that are
`
`imp°rtan”° "mg things’
`
`0 DNA
`
`(deoxyribonuclelc
`acid)
`. RNA (ribonucleic
`acid)
`
`These molecules are also
`polymers of smaller units
`called nucleotides; each
`nucleotide consist of a
`sugar (ribose or
`
`(Sugar)
`
`‘
`
`‘
`
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`
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`
`RNA
`
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`
`http://sph.bu.edu/otlt/MPH—Modules/PH/PH709_A_Ce1lular_World/PH709_A_Celiular_*...
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`9/3 0/2013
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`Textron Exhibit 1001 pg. 9
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`A Cellular World
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`Page 10 of21
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`deoxyribose), a phosphate
`group, and one of several "bases" that are either purines or pyrimidines. Alternating sugar molecules and phosphate
`groups are bonded together to form the backbone of the nucleic acid, and a purine or pyrimidine base is bonded to
`each of the sugars, as illustrated on the right.
`
`There are several differences between DNA and RNA.
`
`o DNA contains the sugar deoxyribose, while RNA contains the sugar ribose.
`o DNA consists of two nucleotide chains that are bonded to together by weak hydrogen bonds between
`complementary base pairs. The double strands are wrapped to form a double helix.
`o The bases found in DNA are limited to adenine, cytosine, guanine, and thymine; RNA has adenine, cytosine,
`and guanine, but hase another base called uracil instead of thymine.
`
`The cells of living organisms have chromosomes which contain an inherited code for synthesizing all of the proteins
`that the organism produces. in essence, each chromosome is a gigantic molecule of double stranded DNA wound
`tightly into a double helix. A single chromosome contains thousands of genes, segments of DNA that encode for
`specific proteins. In a highly regulated process, cellular enzymes can unwind a particular segment (gene). and other
`enzymes move along a gene using one strand of DNA as a template to synthesize a complementary strand of
`messenger RNA. This newly synthesized messenger RNA will then leave the cell nucleus and move to the
`cytoplasm of the cell where the RNA will in turn be used as a template to synthesize a specific protein.
`
`This process will be clearer when we explore it in more detail in another online module. For the time being the video
`below provides an overview of this process that will be helpful.
`
`An Overview of Transcription and Translation
`
`This short animation from the Discovery Channel provides a nice overview of the transcription and translation.
`Transcription is the process by which a gene, segment of DNA that encodes for a specific protein, serves as a
`template for the synthesis of a messenger RNA (mRNA) for that specific protein. Transcription takes place inside
`the cell nucleus where chromosomal DNA is located. The mRNA then leaves the nucleus through special pores in
`the membrane of the nucleus. Once the mRNA emerges from the nucleus, it attaches to a two part structure called
`a ribosome, which consists of ribosomal RNA (rRNA). Enzymes also attach to the ribosomal complex and aid in the
`process of translation, in which the coded sequence of bases on the mRNA is translated and directs the synthesis
`of a chain of amino acids, which are the building blocks of proteins.
`
`Proteins
`
`Proteins are another class of enormously diverse organic molecules
`that are made from multiple units of simpler molecules arranged in
`chains. All proteins are made from combinations of the 20 amino acids
`show below. As shown on the right, each of these 20 amino acids has
`a central carbon (the alpha carbon) bonded to an amino group (-NH2
`i.e., nitrogen bonded to two hydrogens) at one end and a carboxyl
`group ( -COOH) at the other end. What distinguishes one amino acid
`from another is the side chain of atoms that is also bonded to the
`alpha carbon (designated "R-group on the right).
`
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`
`Textron Exhibit 1001 pg. 10
`
`http://sph.bu.edu/otlt/MPH—Modules/PH/PH709_A_Cellular_Wor1d/PH709_A_Cellular_...
`
`9/30/2013
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`

`
`A Cellular World
`
`Page 11 of2l
`
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`The primary structure of proteins results from
`linking together various combinations of these 20
`amino acids with peptide bonds, which link the
`carboxyl group of one amino acid to the amino
`group of another amino acid. Proteins are
`sometimes referred to as polypeptides because
`they consist of chains of amino acids. The chains
`can be just a few amino acids long, or they can
`consist of chains of a thousand of amino acids or
`more.
`
`(The image on the right is from
`http://www.accessexcel|ence.com/AB/GG/Fig_5.02.jpg)
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709_A__Ce1lu1ar_World/PH709_A__Ce1lular_...
`
`9/30/2013
`
`Textron Exhibit 1001 pg. 11
`
`

`
`A Cellular World
`
`Page 12 of 21
`
`Secondary Structure of Proteins
`
`(cl) Primary ‘structure
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`Proteins are more than just strings of amino acids,
`however. There are attractive and repulsive forces among
`the amino acids in the chain that determine the secondary
`structure of the protein. For example, the hydrogen on the
`amino group of one amino acid can form a weak "hydrogen
`bond’ to the oxygen atom in the carboxyl group of another
`amino acid elsewhere on the chain. Hydrogen bonding can
`cause portions of the polypeptide chain to form zig-zag
`sections called "beta sheets" (which are very prominent in
`the protein fiber in silk, for example), and it can also cause
`sections of the polypeptide to twist into a cork screw-
`shaped structure called an "alpha he/ix." Other sections of
`a polypeptide may be referred to as "random coils"
`because they fold but do not have a regular structural
`shape.
`
`Proteins also have a tertiam level of structure as a result
`of ionic, hydrogen, or covalent bonds between the “—R"
`groups of the amino acids. As a result, alpha helical
`segments, beta pleated sheets, and random coils fold upon
`themselves. Folding and placement in a cell will also be
`influenced by the polarity of the amino acids. Some amino
`acids have side chains that are po_|ar and others have non-
`.
`.
`.
`.
`.
`polar side chains. If some sections of the chain contain
`mostly non-polar amino acids, while other sections contain
`mostly polar amino acids, the non-polar sections will self-
`associate in the interior of the molecule away from water, '
`and the polar sections will be arrayed on the exterior of the
`molecule.
`
`
`
`(C) Tertiary structure
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`Finally, guaternagy structure refers to the association of two or more polypeptide chains or subunits into a larger
`entity. For example, the hemoglobin molecule (shown in (d) to the left) consists of two alpha subunits and two beta
`subunits; each of these four polypeptide chains has a binding site for oxygen. Transport proteins in cell membranes
`frequently consist of multiple subunits as well.
`
`amino acid side chains
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`The three
`dimensional
`structure of
`
`proteins
`goes hand
`1” ham with
`
`the three
`dimensional
`shape of a
`protein (its
`conformation)
`may change
`depending
`on changes
`in its local
`environment,
`
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`
`http://sph.bu.edu/otlt/MPH—Modules/PH/PH709__A_Cellular_Wor1d/PH709_A_Cellu1ar_...
`
`9/30/2013
`
`Textron Exhibit 1001 pg. 12
`
`

`
`A Cellular World
`
`Page 13 of 21
`
`and this also may relate to its function. To illustrate, consider the function of an enzyme whose purpose is to cleave
`the phosphate groups from a molecule called cyclic AMP. The enzyme is depicted in the figure to the right. The
`drawings on the left side of the figure show the enzyme folding into its quaternary conformation (folded protein), and
`the drawing on the right is a close up of the binding site, showing a molecule of cyclic AMP (pink shading) nestled in
`the arms of the binding site. Chemical groups on the cyclic AMP (the substrate) are interacting with chemical groups
`on the enzyme through ionic and hydrogen bonds. The binding site is specific for cyclic AMP, which fits into the
`protein binding site in much the same way that a key fits into a specific look. This interaction then causes the
`conformation of the enzyme to change, and this bends the cyclic AMP in a way that facilitates cleavage of the
`phosphate group. Once this occurs, the two resulting products are released, and the enzyme reverts back to its
`resting conformation. (illustration adapted from
`http://accessexceilence.org/RCNL/GG/ecb/protein_binding_site.php )
`
`The three dimensional shape of proteins and this concept of a specific binding site is relevant not only for the
`interaction of enzymes and their substrates, but also for receptors which bind chemical signals in a specific way
`(histamine receptor, below left), and for antibodies that bind to specific antigens based on their shape (below right),
`and for the binding of insulin to its receptor, which triggers a sequence of events that result in the insertion of
`glucose transporters into the plasma membrane (bottom image).
`
`
`
`Antibody
`Binding Sites
`
`functions.
`
`As you will
`see in the
`next section,
`the structure
`of proteins
`enables them
`to serve a
`
`wide variety of
`
`http://sph.bu.edu/otlt/MPH—Modules/PH/PH709_A_Cellular_World/PH709_A_Ce.liular_. ..
`
`9/3 0/2013
`
`Texlron Exhibit 1001 pg. 13
`
`

`
`A Cellular World
`
`Page 14 of 21
`
`insulin
`
`Outside of Cell
`
`
`
`
`Qoélose
`
`The Functions of Proteins
`
`Oxygen Transport
`
`Each of us has tens of thousands of proteins, which serve a variety of functions, and each protein has a unique
`three-dimensional structure that specifies its function. For example, hemoglobin is a protein found in red blood cells,
`which plays a key role in oxygen transport; it has 4 subunits of two distinct types (2 alpha and 2 beta subunits).
`
`‘ quaternary strucmira,
`[aggregation call‘ we or mere easrtldm}
`
`from http://gened.emc.maricopa.edu/bio/bio181/BIOBK/3_14d.jpg
`
`Sickle Cell Disease
`
`The critical relationship between protein structure and function is dramatically illustrated by
`sickle cell anemia, an inherited disease seen in people whose ancestors came from Africa,
`the Middle East, the Mediterranean, or India. In the U.S. about 4 out of every 1,000 African
`Americans has sickle cell disease (about 80,000 people), and about 10% carry the sickle cell
`trait.
`
`
`amino acid glutamate. Unlike glutamate, the side
`
`People with sickle cell disease an abnormal type of
`hemoglobin, called hemoglobin 8 (instead of normal
`hemoglobin A). Hemoglobin S differs from
`hemoglobin A in that the amino acid va/ine is found
`at position number 6 in the beta chain instead of the
`
`http://sph.bu.edu/otlt/MPH-Modules/PH/PH709__A_Cellu1ar_World./PH709*A_Cellu1ar__...
`
`9/30/2013
`
`Textron Exhibit 1001 pg. 14
`
`

`
`A Cellular World
`
`Page 15 of 21
`
`chain of valine is very non—po|ar and creates a sticky patch on the outside of each of the beta
`chains. There is a complementary sticky patch elsewhere on the hemoglobin, but it is masked
`as long as the hemoglobin molecules are bound to oxygen. However, if large numbers of
`hemoglobin molecules become deoxygenated, the sticky sites created by the abnormal
`valines begin to bind to the complementary sticky site on other hemoglobin molecules. This
`forms long aggregates of hemoglobin that distort the red blood cell and give it a characteristic
`sickle shape. This causes red cells to aggregate and impairs their ability to circulate through
`small blood vessels (arterioles and capillaries). and it also makes them fragile, shortening
`their life span and leading to anemia.
`
`Acute exacerbations referred to as "sickle cell crises" are sometimes triggered by
`deoxygenation of hemoglobin, for example, after rigorous exercise or infections. Sickllng can
`be very extensive and result in inadequate blood flow to organs with severe pain and
`
`complications such as stroke. kidney damage and breathing problems.
`
`Proteins as Enzymes
`
`Some proteins function as
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`biochemical reactions.
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`Enzymes facilitate
`biochemical reactions and
`
`speed them up enormously,
`making them as much as a
`million times faster. There
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`are thousands of enzymes,
`and each type facilitates a
`specific biochemical
`reaction. In other words, a
`given enzyme only acts on
`specific reactant molecules
`(substrates) to produce a
`specific end product or products. The diagram to the right illustrates enzymatic cleavage of the disaccharide lactose
`(the substrate) into the monosaccharides galactose and glucose.
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`The three-dimensional shape of the enzyme will include
`a very specific binding site that the substrate will fit into
`very precisely, in much the same way that a key fits a
`specific lock. Once the substrate is bound the enzyme
`cleaves the substrate and the products are released.
`While this cartoon illustrates cleavage of a substrate,
`many enzymes synthesis new biochemicals by binding
`two substrates together to form a new product. A
`particular cell may have thousands of distinct enzymes
`catalyzing many different reactions.
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