Chapter 25: Metabolism

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Chapter 25 Metabolism
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Introduction to Cellular Metabolism
Formation of Organic Molecules
Energy production begins in cytosol
Energy is captured to produce ATP
Figure 251
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Energy

• Large food molecules contain energy
• Energy in the form of chemical bonds
• Work required to liberate energy
• ATP breaking the P bond provides
• energy for cells
• ATP? ADP P free energy from food
• Food Energy ADP P ? ATP
• (This ATP permits anabolism)

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Energy

• Cells break down organic molecules to obtain
  energy
• used to generate ATP
• Most energy production takes place in
  mitochondria

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Essential Materials

• Oxygen
• absorbed at the lungs
• Water
• Nutrients absorbed at digestive tract
• vitamins
• mineral ions
• organic substrates

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Materials Transport

• Cardiovascular system
• carries materials through body
• Materials diffuse
• from bloodstream into cells

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Metabolism

• Refers to all chemical reactions in an organism
• Includes all chemical reactions within cells
• Provides energy to maintain homeostasis and
  perform essential functions

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Essential Metabolic Functions

• Metabolic turnover
• periodic replacement of cells organic components
• Growth and cell division
• Special processes
• secretion
• contraction
• propagation of action potentials

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The Nutrient Pool

• Contains all organic building blocks cell needs
• to provide energy
• to create new cellular components
• Is source of substrates for catabolism and
  anabolism
• Catabolism
• Is the breakdown of organic substrates
• Releases energy used to synthesize high-energy
  compounds (e.g., ATP)
• Anabolism
• Is the synthesis of new organic molecules via
  forming new chemical bonds

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Nutrient Use in Cellular Metabolism
Figure 252 (Navigator)
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Organic Compounds

• Glycogen (carbohydrates)? short carbon chains
• most abundant storage carbohydrate
• a branched chain of glucose molecules
• Triglycerides? fatty acids and glycerol
• most abundant storage lipids
• primarily of fatty acids
• Proteins? amino acids
• most abundant organic components in body
• perform many vital cellular functions

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KEY CONCEPT

• There is an energy cost to staying alive
• Even at rest cells must spend ATP to
• perform routine maintenance
• remove and replace structures and components
• Cells spend additional energy for vital
  functions
• growth
• secretion
• contraction

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Oxidation-Reduction Reactions (Redox Rxns)

• Oxidation the removal of electrons (Or addition
  of oxygen)
• Reduction the addition of electrons
• These reactions are always coupled
• One molecule must be oxidized while another is
  reduced
• A-e B ? A B-e
• Oxidized molecule (A) Loses energy OIL
• Reduced molecule (B) Gains energy RIG

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Oxidation-Reduction Reactions (Redox Rxns)

• Cells perform dehydrogenation reactions
• Hydrogen (1 proton 1 electron) is exchanged
  instead of a free electron, but this is still a
  redox reaction
• Catabolism of large molecules result in reduced
  carrier compounds
• e.i. ADP ? ATP NAD ? NADH FAD ? FADH2
• These reduced compounds are later oxidized to
  generate ATP

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ATP Production

• Requires the addition of a phosphate to ADP
• Two Methods for ATP Productions
• Substrate Level Phosphorylation
• - High energy phosphate is transferred directly
  from a substrate to ADP forming ATP
• Oxidative Phosphorylation
• Electrons are transferred from an organic
  compound to a cofactor carrier molecule (e.g.
  NAD)
• Electrons are passed through other carriers (the
  electron transport chain) to a final acceptor
  (oxygen)
• The passing of electrons releases energy that is
  harvested to add a phosphate to ADP
• Process is called chemiosmosis.

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What are the basic steps in glycolysis, the TCA
cycle, and the electron transport system?
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Carbohydrate Catabolism (Metabolism)

• Carbohydrates are the primary source of cellular
  energy for most organisms
• Glucose is the most commonly used carbohydrate
  and will always be used first
• Generates ATP and other high-energy compounds by
  breaking down carbohydrates
• glucose oxygen ? carbon dioxide water ?

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Carbohydrate Catabolism (Metabolism)

• Two methods for ATP productions via catabolism of
  glucose
• Cellular Respiration
• Requires oxygen to serve as the final electron
  acceptor in a series of redox reactions
• Generate ATP by oxidative phosphorylation
• Most efficient method of ATP production
• 1 glucose generates 36 ATP
• Involves reaction performed inside the
  mitochondria

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Carbohydrate Catabolism (Metabolism)

• Two methods for ATP productions via catabolism of
  glucose
• 2. Fermentation
• Requires an organic molecule to serve as the
  final electron acceptor
• Can be done in the absence of oxygen
• ATP is synthesized using substrate level
  phosphorylation
• Less efficient, 1 glucose generates 2 ATP
• In humans, results in lactic acid

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Anaerobic Vs. Aerobic RespirationGlycolysis

• Anaerobic reactions Fermentation
• Do not require oxygen
• Example Glycolysis
• Breaks down glucose in cytosol
• into smaller molecules used by mitochondria
• Aerobic reactions Cellular Respiration
• Occur in mitochondria
• consume oxygen
• produce ATP

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Aerobic Respiration of GlucoseC6H12O6 6O2 ? 6
CO2 6H2O

• Three Stages
• Glycolysis
• Oxidation of glucose to pyruvic acid
• Some ATP and NADH produced
• Citric Acid Cycle
• Oxidation of acetyl to carbon dioxide
• Some ATP, NADH and FADH produced
• Electron Transport Chain
• NADH and FADH2 are oxidized providing electrons
  for redox reactions
• coenzymes that function to transport electrons in
  the form of hydrogen
• Reduce oxygen to generate ATP
• Majority of ATP is produced at this step

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Nutrient Use in Cellular Metabolism
Figure 252 (Navigator)
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Glycolysis (Anaerobic Process)

• Does not require oxygen
• Occurs in cytoplasm
• 10 step metabolic pathway
• Catabolizes and oxidizes one 6-carbon glucose
  molecule into two 3-carbon pyruvic acid molecules
• Generates 2 ATP by substrate level
  phosphorylation
• Many cells can survive on glycolysis alone
• Not very efficient
• Generates lactic acid as a waste product
• Needs to be removed and processed to prevent
• Drastic alterations in pH
• Loss of homeostasis

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Glycolysis Factors

• Glucose molecules
• Cytoplasmic enzymes
• ATP and ADP
• Inorganic phosphates
• NAD (coenzyme)

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Two Stages in Glycolysis

• Preparatory Stage
• Enzyme phosphorylates last (sixth) carbon atom of
  glucose molecule
• Glucose-6-phosphate is formed using 1 ATP
  molecule
• - traps glucose molecule within cell
• Fructose 1,6-bisphosphate is formed using 1 ATP
• Therefore, two ATP molecules are used to
  phosphorylate one 6-carbon glucose and catabolize
  it into two 3-carbon molecules

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Two Stages in Glycolysis

• Energy Conservation Stage
• the two 3-carbon molecules are oxidized to
  generate two 3-carbon pyruvic acid molecules
• Two NAD molecules are reduced to two NADH
  molecules
• 4 ATP molecules are produced by substrate level
  phosphorylation
• net gain 2 ATP per 1 glucose

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Summary of Glycolysis

• 1 glucose 2 NAD 2 ADP 2P ?
• 2 pyruvic acid 2 NADH 2H 2 ATP

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Aerobic Reactions

• If oxygen supplies are adequate
• mitochondria absorb and break down pyruvic acid
  molecules

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Mitochondrial Membranes

• Outer membrane
• contains large-diameter pores
• permeable to ions and small organic molecules
  (pyruvic acid)
• Inner membrane
• contains carrier protein
• moves pyruvic acid into mitochondrial matrix
• Intermembrane space
• separates outer and inner membranes

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Mitochondrial ATP Production

• H atoms of pyruvic acid
• are removed by coenzymes
• are primary source of energy gain
• C and O atoms
• are removed and released as CO2
• process of decarboxylation

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The TCA Cycle
TCA Cycle
PLAY
Figure 254a (Navigator)
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Decarboxylation

• Preparation of the Citric Acid Cycle
• First step in aerobic process of glucose
  metabolism (oxygen is necessary)
• 3 carbon pyruvic acid is decarboxylated into
  carbon dioxide and a 2 carbon acetyl
• Acetyl is attached to coenzyme A (serves as a
  carrier) and one NAD is reduced to NADH
• Occurs in the matrix of the mitochondria

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Summary of Decarboxylation

• 2 pyruvic acid 2 NAD 2 CoA ?
• 2 Acetyl CoA 2 CO2 2 NADH

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Citric Acid Cycle

• a.k.a. Krebs Cycle or Tricarboxylic Acid Cycle
• Aerobic metabolism of glucose involves
• 8 enzymatic reactions occurring in the
  mitochondrial matrix
• Function to reduce the coenzyme NAD and FAD
• 2-carbon acetyl 4-carbon and 2 CO2 molecules
• At the same time oxaloacetic acid ?
• 
  6-carbon citric acid
• Oxidation and decarboxylation reactions
• Catabolize the 6-carbon citric acid back into a
  4-carbon oxaloacetic acid
• 3 NAD and 1 FAD are reduced into 3 NADH and 1
  FADH2
• 1 ATP is produced by substrate level
  phosphorylation

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The TCA Cycle
Figure 254b
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Citric Acid Cycle

• Remember
• 1 glucose ? 2 pyruvic acid ?
• 2 acetyl so this cycle
  will run twice
• 2Acetyl Co A 6NAD 2FAD 2ADP
• 2P 4H20 ?
• 2CoA 4CO2 6NADH 4H
• 2FADH2 2ATP

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Oxidative Phosphorylation
Figure 255a (Navigator)
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Oxidative Phosphorylation
Occurs on a membrane, the mitochondrial cristae,
to generate most of the ATP produced from glucose
Figure 255b
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Oxidative Phosphorylation

• Is the most important mechanism for generation of
  ATP within the mitochondria
• Produces more than 90 of ATP used by body
• Requires oxygen, electrons, and coenzymes
• rate of ATP generation is limited by oxygen or
  electrons
• Cells obtain oxygen by diffusion from
  extracellular fluid
• Results in 2 H2 O2 ??2 H2O

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The Electron Transport System (ETS)

• Key reaction in oxidative phosphorylation
• Is in inner mitochondrial membrane
• Coenzymes from the previous reactions pass
  electrons (which transfer energy) to a series of
  electron carrier molecules
• Molecules carry out redox reactions resulting in
  the chemiosmotic generation of ATP

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The Electron Transport System (ETS)

• Three classes of carrier molecules
• FMN (flavin mononucleotide) protein flavin
  coenzyme
• Coenzyme Q nonprotein
• Cytochromes protein an iron group
• - Most common

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Events of the Electron Transport Chain

• NAD and FAD collected energy in the form of
  hydrogens (electrons) from organic molecules
  during Glycolysis, Decarboxylation, and the
  Citric Acid Cycle becoming that reduced forms
  NADH and FADH2
• NAD FAD ? NADH FADH2
• NADH and FADH2 are oxidized and pass hydrogens
  (electrons and protons) to the electron transport
  chain consisting of flavoproteins, cytochromes,
  and coenzyme Q.
• NADH FADH2 ? NAD FAD
• As electrons are passed along the chain,
  protons are pushed out through the membrane.
  This sets up a concentration gradient with
  protons ( charge) on the outside and electrons
  (- charge) on the inside

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Events of the Electron Transport Chain

• At the end of the chain the electrons are
  accepted by oxygen creating an anion (O-) inside,
  which has a strong affinity for the cations (H)
  outside.
• Chemiosmosis generates ATP
• - H from the outside moves toward O-
  on the inside through
• special membrane channels that are
  coupled to ATP
• synthase
• - High-energy diffusion of H drives the
  reaction
• ADP P ? ATP.
• a. Energy from 1 NADH from
  glycolysis generate 2 ATP
• b. Energy from 1 NADH from decarboxylation
  and the
• citric acid cycle generate 3
  ATP
• c. Energy from 1 FADH2 generate 2 ATP for
  a total of
• 32 ATP
• 5. H combines with O- inside the
  mitochondria creating water (H2O)

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Oxidative Phosphorylation
Occurs on a membrane, the mitochondrial cristae,
to generate most of the ATP produced from glucose
Figure 255b
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Summary of Electron Transport

• 2 NADH from glycolysis 2 NADH from
  decarboxylation 6 NADH from Citric Acid Cycle
  2 FADH2 from Citric Acid Cycle 6 O2 32 ATP
  32 P ?
• 12 H2O 32 ATP 10 NAD
  2 FAD

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Final Summary of Aerobic Respiration

• C6H12O6 6 O2 36 ADP 36 P ?
• 6 CO2
  6 H2O 36 ATP
• 36 ATP
• 2 from Glycolysis in cytoplasm
• 2 from Citric Acid Cycle by substrate level
  phosphorylation in matrix of mitochondria
• 32 from Electron Transport by oxidative
  phosphorylation in the cristae of the mitochondria

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Energy Yield of Aerobic Metabolism
Figure 256
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Lipid Catabolism BetaOxidation
Figure 258 (Navigator)
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Lipolysis Lipid Catabolism

• Hydrolyzes triglycerides (fat storage) ?
• 
  glycerol and three fatty acids
• Glycerol
• Glycerol ? pyruvic acids in the cytoplasm
• Pyruvic acid catabolized through TCA in
  mitochondria
• Fatty Acids
• Fatty acids are catabolized by beta-oxidation
  into acetyl-CoA
• In mitochondria to enter the TCA as two-carbon
  fragments
• For each two-carbon fragment of fatty acid
  produced by beta-oxidation, the cell can generate
  17 molecules of ATP
• This is 1.5 times the energy production as with
  glucose
• Generates more energy but requires more oxygen
• Occurs much more slowly than equal carbohydrate
  metabolism

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Amino Acid Catabolism
Figure 2510 (Navigator)
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Protein and Amino Acid Catabolism

• 1. Protein ? amino acids
• 2. Amino group (-NH2) is removed from amino acid
  in process called deamination
• Requires vitamin B6
• 3. Amino group is removed with conjunction with
  a hydrogen creating ammonia (NH3)
• Toxic
• 4. Liver converts the NH3 ? urea
• Harmless and excreted by the kidney
• 5. Remaining amino acid carbon chains are used
  at various stages in the Citric Acid Cycle to
  generate ATP
• Amount of ATP produced varies

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Protein and Amino Acid Catabolism

• Not a Practical Source of Quick Energy
• Typically only used in starvation situations
• Harder to break apart than carbohydrates or
  lipids
• Proteins are structural and functional parts of
  every cell
• Thus tend to only be used when no other energy
  source is available
• Amino acids are simply recycled by hydrolysis of
  peptide bonds in one protein, to be reassembled
  by dehydration synthesis into the next.

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Nucleic Acid Catabolism

• DNA is never catabolized for energy
• RNA can be broken down into
• Simple sugars
• Nitrogenous bases
• Sugars
• Metabolized in glycolysis but only the pyrimidine
  bases (uracil and cytosine) can be processed in
  the TCA cycle
• Purines (adenine and guanine) are deaminated and
  excreted as uric acid making RNA metabolism very
  inefficient
• Typically nucleotides are simply recycled into
  new nucleic acid molecules and are not used for
  energy production

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Pathways of Catabolism and Anabolism
Figure 2512
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What is the primary role of the TCA cycle in the
production of ATP?

1. break down glucose
2. create hydrogen gradient
3. phosphorylate ADP
4. transfer electrons from substrates to coenzymes

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How would a decrease in the level of cytoplasmic
NAD affect ATP production in mitochondria?

1. ATP production would increase.
2. ATP production would decrease.
3. ATP production would fluctuate randomly.
4. ATP is not produced in mitochondria.

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How would a diet that is deficient in pyridoxine
(vitamin B6) affect protein metabolism?

1. It would interfere with protein metabolism.
2. It would enhance protein metabolism.
3. It would cause the use of different coenzymes.
4. Pyridoxine is not involved in protein metabolism.

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Elevated levels of uric acid in the blood can be
an indicator of increased metabolism of which
organic compound?

1. nucleic acids
2. proteins
3. carbohydrates
4. lipids

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SUMMARY

• Cellular metabolism
• Catabolism and Anabolism
• Carbohydrate metabolism
• Glycolysis
• Cellular Respiration
• Mitochondrial ATP production
• Lipid catabolism (Beta-oxidation)
• Amino acid catabolism
• Protein synthesis