Chapter 4 Cellular Metabolism

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Chapter 4 Cellular Metabolism
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Cells and the Flow of Energy

• Energy is the ability to do work.
• Living things need to acquire energy this is a
  characteristic of life.
• Cells use acquired energy to
• Maintain their organization
• Carry out reactions that allow cells to develop,
  grow, and reproduce

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Forms of Energy

• There are two basic forms of energy.
• Kinetic energy is the energy of motion.
• Potential energy is stored energy.
• Food eaten has potential energy because it can be
  converted into kinetic energy.
• Potential energy in foods is chemical energy.
• Organisms can convert chemical energy into a form
  of kinetic energy called mechanical energy for
  motion.

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Two Laws of Thermodynamics

• The flow of energy in ecosystems occurs in one
  direction energy does not cycle.
• The two laws of thermodynamics explain this
  phenomenon.
• First Law Energy cannot be created or destroyed,
  but it can be changed from one form to another.
• Second Law Energy cannot be changed from one
  form to another without loss of usable energy.

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Flow of energy
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• Energy exists in several different forms.
• When energy transformations occur, energy is
  neither created nor destroyed but there is always
  loss of usable energy, usually as heat.
• For this reason, living things depend on an
  outside source of energy.
• The ultimate source of energy for ecosystems is
  the sun, and this energy is passed from plants to
  animals.

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Cells and Entropy

• The term entropy is used to indicate the relative
  state of disorganization.
• Cells need a constant supply of energy to
  maintain their internal organization.
• Complex molecules like glucose tend to break
  apart into their building blocks, in this case
  carbon dioxide and water.
• This is because glucose is more organized, and
  thus less stable, than its breakdown products.
• The result is a loss of potential energy and an
  increase in entropy.

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Cells and entropy
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Metabolic Reactions and Energy Transformations

• Metabolism is the sum of all the chemical
  reactions that occur in a cell.
• Reactants are substances that participate in a
  reaction products are substances that form as a
  result of a reaction.
• A reaction will occur spontaneously if it
  increases entropy.
• Biologists use the term free energy instead of
  entropy for cells.

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• Free energy, G, is the amount of energy to do
  work after a reaction has occurred.
• ?G (change in free energy) is calculated by
  subtracting the free energy of reactants from
  that of products.
• A negative ?G means the products have less free
  energy than the reactants, and the reaction will
  occur spontaneously.

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• Exergonic reactions have a negative ?G and energy
  is released.
• Endergonic reactions have a positive ?G and occur
  only if there is an input of energy.
• Energy released from exergonic reactions is used
  to drive endergonic reactions inside cells.
• ATP is the energy carrier between exergonic and
  endergonic reactions.

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ATP Energy for Cells

• ATP (adenosine triphosphate) is the energy
  currency of cells.
• ATP is constantly regenerated from ADP (adenosine
  diphosphate) after energy is expended by the
  cell.
• Use of ATP by the cell has advantages
• 1) It can be used in many types of reactions.
• 2) When ATP ? ADP P, energy released is
  sufficient for cellular needs and little energy
  is wasted.

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• 3) ATP is coupled to endergonic reactions in such
  a way that it minimizes energy loss.
• ATP is a nucleotide made of adenine and ribose
  and three phosphate groups.
• ATP is called a high-energy compound because a
  phosphate group is easily removed.

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The ATP cycle
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Coupled Reactions

• In coupled reactions, energy released by an
  exergonic reaction drives an endergonic reaction.

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Coupled reactions
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Function of ATP

• Cells make use of ATP for
• Chemical work ATP supplies energy to synthesize
  macromolecules, and therefore the organism
• Transport work ATP supplies energy needed to
  pump substances across the plasma membrane
• Mechanical work ATP supplies energy for
  cellular movements

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Two types of metabolic reactions

• Anabolism
• larger molecules are made
• requires energy

• Catabolism
• larger molecules are broken down
• releases energy

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Anabolism
Anabolism provides the substances needed for
cellular growth and repair

• Dehydration synthesis
• type of anabolic process
• used to make polysaccharides, triglycerides, and
  proteins
• produces water

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Anabolism
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Catabolism
Catabolism breaks down larger molecules into
smaller ones

• Hydrolysis
• a catabolic process
• used to decompose carbohydrates, lipids, and
  proteins
• water is used
• reverse of dehydration synthesis

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Catabolism
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Metabolic Pathways and Enzymes

• Cellular reactions are usually part of a
  metabolic pathway, a series of linked reactions,
  illustrated as follows
• E1 E2 E3 E4 E5
  E6 A ? B ? C ? D ? E ? F ?
  G
• Here, the letters A-F are reactants or
  substrates, B-G are the products in the various
  reactions, and E1-E6 are enzymes.

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• An enzyme is a protein molecule that functions as
  an organic catalyst to speed a chemical reaction.
• An enzyme brings together particular molecules
  and causes them to react.
• The reactants in an enzymatic reaction are called
  the substrates for that enzyme.

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Energy of Activation

• The energy that must be added to cause molecules
  to react with one another is called the energy of
  activation (Ea).
• The addition of an enzyme does not change the
  free energy of the reaction, rather an enzyme
  lowers the energy of activation.

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Energy of activation (Ea)
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Enzyme-Substrate Complexes

• Every reaction in a cell requires a specific
  enzyme.
• Enzymes are named for their substrates
• Substrate Enzyme
• Lipid Lipase
• Urea Urease
• Maltose Maltase
• Ribonucleic acid Ribonuclease

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• Only one small part of an enzyme, called the
  active site, complexes with the substrate(s).
• The active site may undergo a slight change in
  shape, called induced fit, in order to
  accommodate the substrate(s).
• The enzyme and substrate form an enzyme-substrate
  complex during the reaction.
• The enzyme is not changed by the reaction, and it
  is free to act again.

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Control of Metabolic Reactions
Enzymes

• control rates of metabolic reactions

• lower activation energy needed to start reactions

• globular proteins with specific shapes

• not consumed in chemical reactions

• substrate specific

• shape of active site determines substrate

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Control of Metabolic Reactions

• Metabolic pathways
• series of enzyme-controlled reactions leading to
  formation of a product
• each new substrate is the product of the
  previous reaction

• Enzyme names commonly
• reflect the substrate
• have the suffix ase
• sucrase, lactase, protease, lipase

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Control of Metabolic Reactions

• Coenzymes
• organic molecules that act as cofactors
• vitamins

• Cofactors
• make some enzymes active
• ions or coenzymes

• Factors that alter enzymes
• heat
• radiation
• electricity
• chemicals
• changes in pH

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Energy for Metabolic Reactions

• Energy
• ability to do work or change something
• heat, light, sound, electricity, mechanical
  energy, chemical energy
• changed from one form to another
• involved in all metabolic reactions

• Release of chemical energy
• most metabolic processes depend on chemical
  energy
• oxidation of glucose generates chemical energy
• cellular respiration releases chemical energy
  from molecules and makes it available for
  cellular use

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Enzymatic reaction
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Induced fit model
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Factors Affecting Enzymatic Speed

• Enzymatic reactions proceed with great speed
  provided there is enough substrate to fill active
  sites most of the time.
• Enzyme activity increases as substrate
  concentration increases because there are more
  collisions between substrate molecules and the
  enzyme.

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Temperature and pH

• As the temperature rises, enzyme activity
  increases because more collisions occur between
  enzyme and substrate.
• If the temperature is too high, enzyme activity
  levels out and then declines rapidly because the
  enzyme is denatured.
• Each enzyme has an optimal pH at which the rate
  of reaction is highest.

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Rate of an enzymatic reaction as a function of
temperature and pH
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• A cell regulates which enzymes are present or
  active at any one time.
• Genes must be turned on or off to regulate the
  quantity of enzyme present.
• Another way to control enzyme activity is to
  activate or deactivate the enzyme.
• Phosphorylation is one way to activate an enzyme.

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Enzyme Inhibition

• Enzyme inhibition occurs when an active enzyme is
  prevented from combining with its substrate.
• When the product of a metabolic pathway is in
  abundance, it binds competitively with the
  enzymes active site, a simple form of feedback
  inhibition.
• Other metabolic pathways are regulated by the end
  product binding to an allosteric site on the
  enzyme.

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Feedback inhibition
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Enzyme Cofactors

• Presence of enzyme cofactors may be necessary for
  some enzymes to carry out their functions.
• Inorganic metal ions, such as copper, zinc, or
  iron function as cofactors for certain enzymes.
• Organic molecules, termed coenzymes, must be
  present for other enzymes to function.
• Some coenzymes are vitamins.

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Oxidation-Reduction and the Flow of Energy

• Oxidation is the loss of electrons and reduction
  is the gain of electrons.
• Because oxidation and reduction occur
  simultaneously in a reaction, such a reaction is
  called a redox reaction.
• Oxidation also refers to the loss of hydrogen
  atoms, and reduction refers to the gain of
  hydrogen atoms in covalent reactions in cells.

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• These types of oxidation-reduction, or redox,
  reactions are exemplified by the overall
  reactions of photosynthesis and cellular
  respiration.
• The two pathways of photosynthesis and cellular
  respiration permit the flow of energy from the
  sun though all living things.

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Cellular Respiration

• The overall equation for cellular respiration is
  opposite that of photosynthesis
• C6H12O6 6O2 ? 6CO2 6H2O Energy
• In this reaction, glucose is oxidized and oxygen
  is reduced to become water.
• The complete oxidation of a mol of glucose
  releases 686 kcal of energy that is used to
  synthesize ATP.

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Chapter Summary

• Two laws of thermodynamics state that energy
  cannot be created or destroyed, and energy
  transformations result in a loss of energy,
  usually as heat.
• As a result of these laws, we know the entropy of
  the universe is ever increasing, and that it
  takes energy to maintain the organization of
  living things.

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• Metabolism refers to all the chemical reactions
  in the cell.
• Only reactions with a negative free energy occur
  spontaneously.
• Endergonic reactions are thus coupled with
  exergonic reactions.
• Energy is stored in cells in ATP molecules.
• Metabolic pathways are a series of
  enzyme-catalyzed reactions.

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• Each reaction requires a specific enzyme.
• Substrate concentration, temperature, pH, and
  enzyme concentration affect the rates of
  reactions.
• Most metabolic pathways are regulated by feedback
  inhibition.
• Cellular respiration involves oxidation-reduction
  reactions and accounts for the flow of energy
  through all living things.

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Cellular Respiration

• Occurs in three series of reactions
• Glycolysis
• Citric acid cycle
• Electron transport chain

• Produces
• carbon dioxide
• water
• ATP (chemical energy)
• heat

• Includes
• anaerobic reactions (without O2) - produce
  little ATP
• aerobic reactions (requires O2) - produce most
  ATP

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Overview of Cellular Respiration

• Cellular respiration is the step-wise release of
  energy from carbohydrates and other molecules
  energy from these reactions is used to synthesize
  ATP molecules.
• This is an aerobic process that requires oxygen
  (O2) and gives off carbon dioxide (CO2), and
  involves the complete breakdown of glucose to
  carbon dioxide and water.

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• The oxidation of glucose is an exergonic reaction
  (releases energy) which drives ATP synthesis,
  which is an endergonic reaction (energy is
  required).
• The overall equation for cellular respiration
  shows the coupling of glucose breakdown to ATP
  buildup.
• The breakdown of one glucose molecule results in
  a maximum of 36 to 38 ATP molecules, representing
  about 40 of the potential energy within the
  glucose molecule.

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ATP Molecules

• each ATP molecule has three parts
• an adenine molecule
• a ribose molecule
• three phosphate molecules in a chain

• third phosphate attached by high-energy bond

• when the bond is broken, energy is transferred

• when the bond is broken, ATP becomes ADP

• ADP becomes ATP through phosphorylation

• phosphorylation requires energy released from
  cellular respiration

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Cellular respiration
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Phases of Complete Glucose Breakdown

• The oxidation of glucose by removal of hydrogen
  atoms involves four phases
• Glycolysis the breakdown of glucose to two
  molecules of pyruvate in the cytoplasm with no
  oxygen needed yields 2 ATP
• Transition reaction pyruvate is oxidized to a
  2-carbon acetyl group carried by CoA, and CO2 is
  removed occurs twice per glucose molecule

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• Citric acid cycle a cyclical series of
  oxidation reactions that give off CO2 and produce
  one ATP per cycle occurs twice per glucose
  molecule
• Electron transport system a series of carriers
  that accept electrons removed from glucose and
  pass them from one carrier to the next until the
  final receptor, O2 is reached water is produced
  energy is released and used to synthesize 32 to
  34 ATP
• If oxygen is not available, fermentation occurs
  in the cytoplasm instead of proceeding to
  cellular respiration.

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Outside the Mitochondria Glycolysis

• Glycolysis occurs in the cytoplasm and is the
  breakdown of glucose to two pyruvate molecules.
• Glycolysis is universally found in all organisms
  and likely evolved before the citric acid cycle
  and electron transport system.
• Glycolysis does not require oxygen.

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Glycolysis

• series of ten reactions
• breaks down glucose into 2 pyruvic acids
• occurs in cytosol
• anaerobic phase of cellular respiration
• yields two ATP molecules per glucose

• Summarized by three main events
• phosphorylation
• splitting
• production of NADH and ATP

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Energy-Investment Steps

• As glycolysis begins, two ATP are used to
  activate glucose, a 6-carbon molecule that splits
  into two C3 molecules known as PGAL.
• PGAL carries a phosphate group from ATP.
• From this point on, each C3 molecule undergoes
  the same series of reactions.

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Glycolysis

• Event 1 - Phosphorylation
• two phosphates added to glucose
• requires ATP

• Event 2 Splitting (cleavage)
• 6-carbon glucose split into two 3-carbon
  molecules

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Energy-Harvesting Steps

• Oxidation of PGAL now occurs by the removal of
  electrons that are accompanied by hydrogen ions,
  both picked up by the coenzyme NAD
• 2 NAD 4H ? 2 NADH 2 H
• The oxidation of PGAL and subsequent substrates
  results in four high-energy phosphate groups used
  to synthesize ATP in substrate-level
  phosphorylation.

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Glycolysis

• Event 3 Production of NADH and ATP
• hydrogen atoms are released
• hydrogen atoms bind to NAD to produce NADH
• NADH delivers hydrogen atoms to electron
  transport chain if oxygen is available
• ADP is phosphorylated to become ATP
• two molecules of pyruvic acid are produced

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Glycolysis Summary

• Inputs
• Glucose
• 2 NAD
• 2 ATP
• 4 ADP 2 P

• Outputs
• 2 pyruvate
• 2 NADH
• 2 ADP
• 2 ATP (net gain)

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Anaerobic Reactions

• If oxygen is not available -
• electron transport chain cannot accept NADH
• pyruvic acid is converted to lactic acid
• glycolysis is inhibited
• ATP production declines

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Aerobic Reactions

• If oxygen is available
• pyruvic acid is used to produce acetyl CoA
• citric acid cycle begins
• electron transport chain functions
• carbon dioxide and water are formed
• 36 molecules of ATP produced per glucose molecule

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Inside the Mitochondria

• A mitochondrion is a cellular organelle that has
  a double membrane, with an intermembrane space
  between the two layers.
• Cristae are folds of inner membrane that jut out
  into the matrix, the innermost compartment, which
  is filled with a gel-like fluid.
• The transition reaction and citic acid cycle
  occur in the matrix the electron transport
  system is located in the cristae.

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Transition Reaction

• The transition reaction connects glycolysis to
  the citric acid cycle, and is thus the transition
  between these two pathways.
• Pyruvate is converted to a C2 acetyl group
  attached to coenzyme A (CoA), and CO2 is
  released.
• During this oxidation reaction, NAD is converted
  to NADH H the transition reaction occurs
  twice per glucose molecule.

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Citric Acid Cycle

• The citric acid cycle is a cyclical metabolic
  pathway located in the matrix of the
  mitochondria.
• At the start of the citric acid cycle, CoA
  carries the C2 acetyl group to join a C4
  molecule, and C6 citrate results.
• Each acetyl group received from the transition
  reaction is oxidized to 2 CO2 molecules.

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• During the cycle, oxidation occurs when NAD
  accepts electrons in three sites and FAD accepts
  electrons once.
• Substrate-level phosphorylation results in a gain
  of one ATP per every turn of the cycle it turns
  twice per glucose.
• During the citric acid cycle, the six carbon
  atoms in glucose become CO2.
• The transition reaction produces two CO2, and the
  citric acid cycle produces four CO2 per molecule
  of glucose.

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Citric Acid Cycle

• begins when acetyl CoA combines with oxaloacetic
  acid to produce citric acid
• citric acid is changed into oxaloacetic acid
  through a series of reactions
• cycle repeats as long as pyruvic acid and oxygen
  are available

• for each citric acid molecule
• one ATP is produced
• eight hydrogen atoms are transferred to NAD and
  FAD
• two CO2 produced

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Citric acid cycle
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Citric acid cycle inputs and outputs per glucose
molecule

• Inputs
• 2 acetyl groups
• 6 NAD
• 2 FAD
• 2 ADP 2 P

• Outputs
• 4 CO2
• 6 NADH
• 2 FADH2
• 2 ATP

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Electron Transport System

• The electron transport system located in the
  cristae of mitochondria is a series of protein
  carriers, that pass electrons from one to the
  other.
• Electrons carried by NADH and FADH2 enter the
  electron transport system.
• As a pair of electrons is passed from carrier to
  carrier, energy is released and is used to form
  ATP molecules by oxidative phosphorylation.

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• Oxygen receives energy-spent electrons at the end
  of the electron transport system.
• Next, oxygen combines with hydrogen, and water
  forms
• ½ O2 2 e- 2 H ? H2O
• When NADH carries electrons to the first carrier,
  enough energy is released by the time electrons
  are accepted by O2 to produce three ATP two ATP
  are produced when FADH2 delivers electrons to the
  carriers.

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Overview of the electron transport system
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Organization of Cristae

• The electron transport system is located in the
  cristae of the mitochondria and consists of three
  protein complexes and two mobile carriers.
• The mobile carriers transport electrons between
  the complexes, which also contain electron
  carriers.
• The carriers use the energy released by electrons
  as they move down the carriers to pump H from
  the matrix into the intermembrane space of the
  mitochondrion.

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• A very strong electrochemical gradient is
  established with few H in the matrix and many in
  the intermembrane space.
• The cristae also contain an ATP synthase complex
  through which hydrogen ions flow down their
  gradient from the intermembrane space into the
  matrix.
• The flow of three H through an ATP synthase
  complex causes a conformational change, which
  causes the ATP synthase to synthesize ATP from
  ADP P.

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• Mitochondria produce ATP by chemiosmosis, so
  called because ATP production is tied to an
  electrochemical gradient, namely an H gradient.
• Once formed, ATP molecules are transported out of
  the mitochondrial matrix.

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Organization of cristae
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Electron Transport Chain

• NADH and FADH2 carry electrons to the ETC
• ETC series of electron carriers located in
  cristae of mitochondria
• energy from electrons transferred to ATP
  synthase
• ATP synthase catalyzes the phosphorylation of
  ADP to ATP
• water is formed

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Energy Yield from Glucose Metabolism

• Per glucose molecule, there is a net gain of two
  ATP from glycolysis, which occurs in the
  cytoplasm by substrate-level phosphorylation.
• The citric acid cycle, occurring in the matrix of
  mitochondria, adds two more ATP, also by
  substrate-level phosphorylation.

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• Most ATP is produced by the electron transport
  system and chemiosmosis.
• Per glucose molecule, ten NADH and two FADH2 take
  electrons to the electron transport system three
  ATP are formed per NADH and two ATP per FADH2.
• Electrons carried by NADH produced during
  glycolysis are shuttled to the electron transport
  chain by an organic molecule.

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Accounting of energy yield per glucose molecule
breakdown
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Summary of Cellular Respiration
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Summary of Catabolism of Proteins, Carbohydrates,
and Fats
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Carbohydrate Storage

• Excess glucose stored as
• glycogen (primarily by liver and muscle cells)
• fat
• converted to amino acids

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Nucleic Acids and Protein Synthesis
Genetic information instructs cells how to
construct proteins stored in DNA
Gene segment of DNA that codes for one protein
Genome complete set of genes
Genetic Code method used to translate a
sequence of nucleotides of DNA into a sequence of
amino acids
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DNA Structure and Replication

• In the mid-1900s, scientists knew that
  chromosomes, made up of DNA (deoxyribonucleic
  acid) and proteins, contained genetic
  information.
• However, they did not know whether the DNA or the
  proteins was the actual genetic material.

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Structure of DNA

• The structure of DNA was determined by James
  Watson and Francis Crick in the early 1950s.
• DNA is a polynucleotide nucleotides are composed
  of a phosphate, a sugar, and a nitrogen-containing
  base.
• DNA has the sugar deoxyribose and four different
  bases adenine (A), thymine (T), guanine (G), and
  cytosine (C).

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One pair of bases
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• Watson and Crick showed that DNA is a double
  helix in which A is paired with T and G is paired
  with C.
• This is called complementary base pairing because
  a purine is always paired with a pyrimidine.

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• When the DNA double helix unwinds, it resembles a
  ladder.
• The sides of the ladder are the sugar-phosphate
  backbones, and the rungs of the ladder are the
  complementary paired bases.
• The two DNA strands are anti-parallel they run
  in opposite directions.

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DNA double helix
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Replication of DNA

• DNA replication occurs during chromosome
  duplication an exact copy of the DNA is produced
  with the aid of DNA polymerase.
• Hydrogen bonds between bases break and enzymes
  unzip the molecule.
• Each old strand of nucleotides serves as a
  template for each new strand.

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• New nucleotides move into complementary positions
  are joined by DNA polymerase.
• The process is semiconservative because each new
  double helix is composed of an old strand of
  nucleotides from the parent molecule and one
  newly-formed strand.
• Some cancer treatments are aimed at stopping DNA
  replication in rapidly-dividing cancer cells.

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Ladder configuration and DNA replication
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Gene Expression

• A gene is a segment of DNA that specifies the
  amino acid sequence of a protein.
• Gene expression occurs when gene activity leads
  to a protein product in the cell.
• A gene does not directly control protein
  synthesis instead, it passes its genetic
  information on to RNA, which is more directly
  involved in protein synthesis.

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RNA

• RNA (ribonucleic acid) is a single-stranded
  nucleic acid in which A pairs with U (uracil)
  while G pairs with C.
• Three types of RNA are involved in gene
  expression messenger RNA (mRNA) carries genetic
  information to the ribosomes, ribosomal RNA
  (rRNA) is found in the ribosomes, and transfer
  RNA (tRNA) transfers amino acids to the
  ribosomes, where the protein product is
  synthesized.

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Structure of RNA
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• Two processes are involved in the synthesis of
  proteins in the cell
• Transcription makes an RNA molecule complementary
  to a portion of DNA.
• Translation occurs when the sequence of bases of
  mRNA directs the sequence of amino acids in a
  polypeptide.

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The Genetic Code

• DNA specifies the synthesis of proteins because
  it contains a triplet code every three bases
  stand for one amino acid.
• Each three-letter unit of an mRNA molecule is
  called a codon.
• Most amino acids have more than one codon there
  are 20 amino acids with a possible 64 different
  triplets.
• The code is nearly universal among living
  organisms.

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Messenger RNA codons
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Central Concept

• The central concept of genetics involves the
  DNA-to-protein sequence involving transcription
  and translation.
• DNA has a sequence of bases that is transcribed
  into a sequence of bases in mRNA.
• Every three bases is a codon that stands for a
  particular amino acid.

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Transcription

• During transcription in the nucleus, a segment
  of DNA unwinds and unzips, and the DNA serves as
  a template for mRNA formation.
• RNA polymerase joins the RNA nucleotides so that
  the codons in mRNA are complementary to the
  triplet code in DNA.

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Transcription and mRNA synthesis
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Processing of mRNA

• DNA contains exons and introns.
• Before mRNA leaves the nucleus, it is processed
  and the introns are excised so that only the
  exons are expressed.
• The splicing of mRNA is done by ribozymes,
  organic catalysts composed of RNA, not protein.
• Primary mRNA is processed into mature mRNA.

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Function of introns
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Translation

• Translation is the second step by which gene
  expression leads to protein synthesis.
• During translation, the sequence of codons in
  mRNA specifies the order of amino acids in a
  protein.
• Translation requires several enzymes and two
  other types of RNA transfer RNA and ribosomal
  RNA.

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Transfer RNA

• During translation, transfer RNA (tRNA) molecules
  attach to their own particular amino acid and
  travel to a ribosome.
• Through complementary base pairing between
  anticodons of tRNA and codons of mRNA, the
  sequence of tRNAs and their amino acids form the
  sequence of the polypeptide.

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Transfer RNA amino acid carrier
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Ribosomal RNA

• Ribosomal RNA, also called structural RNA, is
  made in the nucleolus.
• Proteins made in the cytoplasm move into the
  nucleus and join with ribosomal RNA to form the
  subunits of ribosomes.
• A large subunit and small subunit of a ribosome
  leave the nucleus and join in the cytoplasm to
  form a ribosome just prior to protein synthesis.

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• A ribosome has a binding site for mRNA as well as
  binding sites for two tRNA molecules at a time.
• As the ribosome moves down the mRNA molecule, new
  tRNAs arrive, and a polypeptide forms and grows
  longer.
• Translation terminates once the polypeptide is
  fully formed the ribosome separates into two
  subunits and falls off the mRNA.
• Several ribosomes may attach and translate the
  same mRNA, therefore the name polyribosome.

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Polyribosome structure and function
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Translation Requires Three Steps

• During translation, the codons of an mRNA
  base-pair with tRNA anticodons.
• Protein translation requires these steps
• Chain initiation
• Chain elongation
• Chain termination.
• Enzymes are required for each step, and the first
  two steps require energy.

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Chain Initiation

• During chain initiation, a small ribosomal
  subunit, the mRNA, an initiator tRNA, and a large
  ribosomal unit bind together.
• First, a small ribosomal subunit attaches to the
  mRNA near the start codon.
• The anticodon of tRNA, called the initiator RNA,
  pairs with this codon.
• Then the large ribosomal subunit joins.

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Initiation
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Chain Elongation

• During chain elongation, the initiator tRNA
  passes its amino acid to a tRNA-amino acid
  complex that has come to the second binding site.
  
• The ribosome moves forward and the tRNA at the
  second binding site is now at the first site, a
  sequence called translocation.
• The previous tRNA leaves the ribosome and picks
  up another amino acid before returning.

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Elongation
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Chain Termination

• Chain termination occurs when a stop-codon
  sequence is reached.
• The polypeptide is enzymatically cleaved from the
  last tRNA by a release factor, and the ribosome
  falls away from the mRNA molecule.
• A newly synthesized polypeptide may function
  along or become part of a protein.

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Termination
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Review of Gene Expression

• DNA in the nucleus contains a triplet code each
  group of three bases stands for one amino acid.
• During transcription, an mRNA copy of the DNA
  template is made.
• The mRNA is processed before leaving the nucleus.
• The mRNA joins with a ribosome, where tRNA
  carries the amino acids into position during
  translation.

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Gene Mutations

• A gene mutation is a change in the sequence of
  bases within a gene.
• Frameshift Mutations
• Frameshift mutations involve the addition or
  removal of a base during the formation of mRNA
  these change the genetic message by shifting the
  reading frame.

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Point Mutations

• The change of just one nucleotide causing a codon
  change can cause the wrong amino acid to be
  inserted in a polypeptide this is a point
  mutation.
• In a silent mutation, the change in the codon
  results in the same amino acid.

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• If a codon is changed to a stop codon, the
  resulting protein may be too short to function
  this is a nonsense mutation.
• If a point mutation involves the substitution of
  a different amino acid, the result may be a
  protein that cannot reach its final shape this
  is a missense mutation.
• An example is Hbs which causes sickle-cell
  disease.

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Sickle-cell disease in humans
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Cause and Repair of Mutations

• Mutations can be spontaneous or caused by
  environmental influences called mutagens.
• Mutagens include radiation (X-rays, UV
  radiation), and organic chemicals (in cigarette
  smoke and pesticides).
• DNA polymerase proof reads the new strand against
  the old strand and detects mismatched pairs,
  reducing mistakes to one in a billion nucleotide
  pairs replicated.

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Transposons Jumping Genes

• Transposons are specific DNA sequences that move
  from place to place within and between
  chromosomes.
• These so-called jumping genes can cause a
  mutation to occur by altering gene expression.
• It is likely all organisms, including humans,
  have transposons.

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Cancer A Failure of Genetic Control

• Cancer is a genetic disorder resulting in a
  tumor, an abnormal mass of cells.
• Carcinogenesis, the development of cancer, is a
  gradual process.
• Cancer cells lack differentiation, form tumors,
  undergo angiogenesis and metastasize.
• Cancer cells fail to undergo apoptosis, or
  programmed cell death.

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Structure of DNA

• two polynucleotide chains
• hydrogen bonds hold nitrogenous bases together
• bases pair specifically (A-T and C-G)
• forms a helix
• DNA wrapped about histones forms chromosomes

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RNA Molecules

• Messenger RNA (mRNA) -
• delivers genetic information from nucleus to the
  cytoplasm
• single polynucleotide chain
• formed beside a strand of DNA
• RNA nucleotides are complementary to DNA
  nucleotides (exception no thymine in RNA
  replaced with uracil)
• making of mRNA is transcription

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RNA Molecules

• Transfer RNA (tRNA) -
• carries amino acids to mRNA
• carries anticodon to mRNA
• translates a codon of mRNA into an amino acid

• Ribosomal RNA (rRNA)
• provides structure and enzyme activity for
  ribosomes

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Protein Synthesis
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134
Protein Synthesis
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135
DNA Replication

• hydrogen bonds break between bases
• double strands unwind and pull apart
• new nucleotides pair with exposed bases
• controlled by DNA polymerase

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136
Mutations
Mutations change in genetic information

• Result when
• extra bases are added or deleted
• bases are changed

May or may not change the protein
Repair enzymes correct mutations
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Clinical Application
Phenylketonuria PKU

• enzyme that breaks down the amino acid
  phenylalanine is missing
• build up of phenylalanine causes mental
  retardation
• treated by diets very low in phenylalanine

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