Transcript Metabolism: Fueling Cell Growth

Metabolism:
Fueling Cell Growth
Chapter 6
Metabolism
 Cells must accomplish two fundamental tasks
to grow

Synthesize new components


Biosynthesis
Harvest energy
 The sum total of chemical reactions of
biosynthesis and energy-harvesting is termed
metabolism
Principles of Metabolism
 Metabolism is broken down into two
components
 Anabolism
 Catabolism
 Catabolism
 Degradative reactions
 Reactions produce energy from
the break down of larger
molecules
 Anabolism
 Reactions involved in the
synthesis of cell components
 Anabolic reactions require energy

Anabolic reactions utilize the
energy produced from catabolic
reactions
Principles of Metabolism
 Harvesting energy
 Energy defined as capacity to do work
 Exists as

Potential energy
 Stored energy

Kinetic energy
 Energy in motion
 Doing work

Energy can be converted from one form to
another


Potential  kinetic
Kinetic  potential
Principles of Metabolism
 Harvesting energy
 Amount of energy available
released from bonds is free
energy
 Energy available to do work
 If reactants have more free
energy than products,
energy is released
 Exergonic reaction
 If products have more
energy that reactants,
energy is consumed
 Endergonic reaction
Principles of Metabolism
 Components of metabolic pathways
 Process occurs in sequence of chemical reactions
 Starting compound is converted to intermediate
molecules and end products
 Intermediates and end products can be used as precursor
metabolites

Metabolic pathways employ critical components to
complete processes
 Enzymes
 ATP
 Chemical energy source
 Electron carriers
 Precursor metabolites
Principles of Metabolism
 Role of enzymes
 Enzymes facilitate each step of metabolic pathway
 They are proteins acting as chemical catalysts
 Accelerate conversion of substrate to product
 Catalyze reactions by lowering activation energy
 Energy required to initiate a chemical reaction
Principles of Metabolism
 Role of ATP
 Adenosine triphosphate (ATP)
 Energy currency of cell
 Negatively charged phosphate groups attached to adenosine
molecule
 Negative charges of phosphate repel
 Create unstable bond that is easily broken releasing energy

ATP created by three mechanism
 Substrate phosphorylation
 Oxidative phosphorylation
 Photophosphorylation
Principles of Metabolism
 Substrate phosphorylation
Uses chemical energy to
add phosphate ion to
molecule of ADP
 Oxidative phosphorylation
 Uses energy from proton
motive force to add
phosphate ion to ADP
 Photophosphorylation
 Utilizes radiant energy
from sun the
phosphorylate ADP to
ATP

Principles of Metabolism
 Role of chemical energy source

Energy source


Compound broken down to release energy
Variety of compounds available
 Glucose most common organic molecule

Harvesting energy requires series of coupled
reactions
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Oxidation-reduction reactions
Principles of Metabolism
 Oxidation-reduction reactions
 Reactions in which one or more electrons is transferred
from one substance to another
 Compounds that LOSE electrons are oxidized
 Termed electron donor

Compounds that GAIN electrons are reduced
 Termed electron carrier

In reactions electrons are removed
 Protons often follow generally in the form of H+ ion
 H+ ion has one proton and no electron
Principles of Metabolism
 Role of electron carriers
 Three different types of electron carriers
 Nicotinamide adenine dinucleotide
 NAD+

Flavin adenine dinucleotide
 FAD

Nicotinamide adenine dinucleotide phosphate
 NADP+

Reduced forms represent reducing power
 Due to usable energy in bonds
 Reduced forms
 NADH
 FADH2
 NADPH
Principles of Metabolism
 Precursor metabolites
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Intermediate products produced in catabolic
pathways
Used in anabolic pathways
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Serve as raw materials for construction of
macromolecules
Principles of Metabolism
 Scheme of metabolism
 Three key pathways
 Central metabolic pathways
 Glycolysis
 Pentose phosphate pathway
 Tricarboxcylic acid cycle

Central pathways are
catabolic and provide
 Energy
 Reducing power
 Precursor metabolites
Principles of Metabolism
 Glycolysis
Oxidizes glucose to two molecules of pyruvate
 Pentose phosphate pathway (PPP)
 Breaks down glucose
 Produces molecules for biosynthesis
 Works in conjunction with glucose degrading pathways
 Tricarboxylic acid cycle (TCA) Krebs Cycle
 Before entering cycle pyruvate enters transition step

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Pyruvate formed in glycolysis and PPP
Cycle turns twice to complete oxidation of one glucose
molecule
Principles of Metabolism
 Respiration vs. fermentation
 Respiration uses reducing power to generate ATP
 NADH and FADH2 transfer electrons to produce proton
motive force
 Allows for recycling of electron carriers

Electrons join with terminal electron acceptor
 Oxygen in aerobic respiration
 Anaerobic respiration uses another inorganic molecule

Fermentation is partial oxidation of glucose
 Produces very little ATP
 Uses pyruvate or derivative as terminal electron acceptor
 Other organisms may use other organic molecules as terminal
electron acceptor
Enzymes
 Act as biological catalysts
 Very specific
 A particular enzyme will only act with one or a limited
number of substrates
 Enzymes do not alter the reactants or products of a
chemical reaction
 Enzymes are not altered by the chemical reaction they
catalyze
 Enzymes are usually named for the substrate they act
on and end in the suffix –ase
 Protease
Enzymes
 Enzyme action
 Enzymes act in two
steps
 Substrate binds to
the active site of
the enzyme to
form an
enzyme/substrate
complex
 A substrate is the
specific substance
on which the
enzyme acts

Products are
formed
 E + S  ES  E + P
 Enzyme is released to bind
new substrate
 Enzymes are regulated
to prevent over
production of product
Enzymes
 Cofactors and coenzymes
 Cofactors
 Non-protein component
reacting with enzyme
 Coenzymes
 Organic cofactors
 Act as carriers for molecules or
electrons
 NAD+, FAD and NADP+ are
coenzymes

Not as specific as enzymes
 May act with numerous
enzymes
Enzymes
 Environmental factors of enzyme activity
 Enzymes function in narrow range of
environmental factors
 Factors affecting enzyme activity are

Temperature
 Increases temperature increases speed of reaction
 Extremely high temperature makes enzyme non
functional

pH
 Enzymes function best at pH just above 7

Salt concentration
 Low salt concentration are most desired
Enzymes
 Allosteric regulation


Regulation regulates production of
product
Regulatory molecule binds to
allosteric site of enzyme


Alters affinity of enzyme to
substrate
Allosteric enzymes initiates activity
of give pathway

Regulation controls metabolic
activity
 Feedback inhibition

End product of pathway acts on
allotter site of enzyme

Shuts pathway down
Enzymes
 Enzyme inhibition

Non-competitive inhibition

Inhibitor and substrate act on different enzyme sites
 Allosteric inhibition
 Feedback inhibition

Competitive inhibition

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Inhibitor competes for active site with substrate
Inhibitor structurally similar to substrate
 Sulfa drugs compete with PABA for active site on enzyme that
produces folic acid
Central Metabolic Pathways
 Pathways modify organic molecules to form
 High energy intermediates to synthesize ATP
 Intermediates to generate reducing power
 Intermediate and end products as precursor
metabolites
 Pathways
 Glycolysis
 Pentose Phosphate Pathway
 Tricarboxylic Acid Cycle
Central Metabolic Pathways
 Glycolysis
 Primary pathway to convert one glucose to two
pyruvate
 10 step process
 Pathway generates
 Two 3-C pyruvate molecules
 Net gain of two ATP
 2 ATP expended to break glucose
 4 ATP harvested

Two molecules reducing power
 NADH

Six different precursor metabolites
 5 intermediates and pyruvate
Glycolysis
Central Metabolic Pathways
 Pentose phosphate pathway

Generates 5 and 7 carbon sugars

Also produces glyceraldehyde 3-phosphate
 Can go into glycolysis for further breakdown

Pathway major contributor to biosynthesis

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Produces reducing power in NADPH
Two vital precursor metabolites
Central Metabolic Pathways
 Transition step
 Links glycolysis to Tricarboxylic Acid Cycle
 Modifies 3-C pyruvate from glycolysis to 2-C acetyl CoA
 CO2 is removed through decarboxylation
 Remaining 2-C acetyl group joined to coenzyme A
 Forms Acetyl CoA
NAD+ is reduced to NADH
Each pyruvate enters transition step
 Reaction occurs twice for one glucose
Yield from transition step
 Reducing power
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 NADH
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Precursor metabolites
 Acetyl CoA
Central Metabolic Pathways
 Tricarboxylic acid cycle
 Completes the oxidation of glucose
 Incorporates acetyl CoA from transition step
 Releases CO2 in net reaction
 Cycle turns once for each acetyl CoA
 Two turns for each glucose molecule
 Cycle produces
 2 ATP
 6 NADH
 2 FADH2
 2 precursor metabolites
Tricarboxylic Acid Cycle
Respiration
 Uses NADH and FADH2 to synthesize ATP

Oxidative phosphorylation

Occurs in electron transport chain
 Generates proton motive force

Combined with ATP synthase
 Uses energy in proton motive force to synthesize
ATP
Respiration
 Electron transport chain
 Group of membrane-embedded electron
carriers
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Arrangement of carriers aids in production of
proton motive force
Four types of electron carriers



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Flavoproteins
Iron-sulfur proteins
Quinones
Cytochromes
Respiration
 Mechanism of proton motive force

Certain carriers accept protons and electrons,
some accept only electrons

Pump protons across membrane
 Creates a proton gradient (proton motive force
 Arrangement of carriers causes protons to be
shuttled across membrane
Respiration
 Electron transport chain of mitochondria
 Chain consists of following components
 Complex I
 A.k.a NADH dehydrogenase complex
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Complex II
 A.k.a succinate dehydrogenase complex

Coenzyme Q
 A.k.a cyrochiome bc, complex
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
Complex III
Cytochrome C
 A.k.a. Cyrochiome c oxidate complex
Complex IV
Each carrier accepts electrons from previous carrier
 In process protons are pumped across membrane
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Electron Transport Chain
of Mitochondria
Respiration
 Electron transport chain of prokaryotes
 Respiration is either aerobic or anaerobic
 In aerobic respiration some prokaryotes have
enzymes equivalent to complex I and II of
mitochondria

Do not have enzyme equivalents of complex III or
cytochrome c
 Use quinones instead (ubiquinone)
 Shuttles electrons directly to terminal electron
acceptor
 Oxygen acts as acceptor when available
Electron Transport Chain
of Prokaryotes (Aerobic)
Respiration
 Electron transport chain in prokaryotes
 Anaerobic respiration is less efficient
 Alternative electron carriers used
 Oxygen does not act as terminal electron acceptor
 Some bacteria use nitrate
 Nitrate converted to nitrite
 Nitrite converted to ammonia
Sulfur-reduce bacteria use sulfate as terminal electron
acceptor
Quinone carrier (menaquinone) produces vitamin K


Respiration
 ATP synthase
 Harvest energy from proton motive force to
synthesize ATP

Permits protons to flow back into cell
 Produces enough energy to phosphorylate ADP 
ATP
 1 ATP is formed from entry of 3 protons

10 protons pumped out per NADH
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
One NADH produces 3 molecules ATP
6 protons pumped out per FADH
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One FADH2 produces 2 molecules of ATP
Respiration
 ATP from oxidative phosphorylation
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ATP produced through re-oxidation of NADH and
FADH2
Maximum theoretical yield

From glycolysis
 2 NADH  6 ATP
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From transition step
 2 NADH  6 ATP
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From TCA
 6 NADH  18 ATP
 2 FADH2  4 ATP
Respiration
 Total ATP yield from prokaryotic aerobic respiration

Substrate phosphorylation

4 ATP
 Net 2 from glycolysis
 2 ATP from TCA

Oxidative phosphorylation
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34 ATP
 6 ATP from glycolysis
 Re-oxidation of 2 NADH
 6 from transition step
 Re-oxidation of NADH
 22 from TCA cycle
 Re-oxidation of NADH and FADH2

Total yield

4 + 34 = 38 (theoretical maximum)
 Eukaryotic cells have theoretical maximum of 36
 2 ATP spent crossing mitochondrial membrane
Fermentation
 Used by organisms that cannot respire

Due to lack of suitable inorganic electron
acceptor or lack of electron transport chain
 ATP produced only in glycolysis

Other steps for consuming excess reducing
power

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Recycles NADH
Fermentation pathways use pyruvate or
derivative as terminal electron acceptor
Fermentation
 End products of fermentation include
 Lactic acid
 Ethanol
 Butyric acid
 Propionic acid
 2,3-Butanediol
 Mixed acids
 All are produced in a series of reaction to produce
appropriate terminal electron acceptors
Catabolism of Other
Organic Compounds
 Cells use variety of organic molecules as
energy sources

Use hydrolytic enzymes to break bonds

Hydrolytic reactions add water to break bonds
Catabolism of Other
Organic Compounds
 Polysaccharides and disaccharides

Starch and cellulose polymers of glucose


Amylases breaks down starch to glucose subunits
Cellulases breaks down cellulose to glucose subunits
 Glucose enters glycolysis for metabolism

Disaccharides are hydrolyzed by specific
disaccharidases

Disaccharides are formed between glucose and other
monosaccharides
 Glucose liberated through hydrolysis enters glycolysis
 Other monosaccharide modified before metabolism
Catabolism of Other
Organic Compounds
 Lipids
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
Simple lipids are combination of fatty acids
and glycerol
Hydrolyzed by lipases

Glycerol is converted to dihydroxyacetone
phosphate
 Molecule enters glycolysis

Fatty acids degraded by β-oxidation
 Transfers 2-C fatty acid units to coenzyme A
 Forms acetyl CoA that enters TCA cycle
Catabolism of Other
Organic Compounds
 Proteins

Hydrolyzed by proteases


Amino group removed through deamination
Remaining carbon skeleton converted to
precursor metabolite
Chemolithotrophs
 Chemolithotrophs able to reduce inorganic chemicals as
source of energy
 Organisms fall into four groups




Hydrogen bacteria
 Oxidize hydrogen gas
Sulfur bacteria
 Oxidize hydrogen sulfide
Iron bacteria
 Oxidized reduced iron
Nitrifying bacteria
 Two groups
 One oxidizes ammonia to nitrite
 One oxidizes nitrite to nitrate
Chemolithotrophs
 Chemolithotrophs generate ATP through oxidative
phosphorylation

Amount of energy gained depends on energy source
and terminal electron acceptor
 Organisms thrive in specific environments
 Particularly where reduced inorganic compounds are
found
 Do not require external carbon source
 Produce organic carbon from inorganic source through
carbon fixation
Photosynthesis
 Photosynthetic organisms harvest energy from
sunlight

Use energy to power synthesis of organic compounds
from CO2
 Photosynthesis has two distinct stages
 Light dependent reactions
 A.k.a light reactions
 Converts light energy to chemical energy
 Light independent reactions
 a.k.a dark reactions
 Uses energy from light reactions to produce organic
compounds
Photosynthesis
 Capturing radiant energy
 Photosynthetic organisms highly visible due to light
capturing pigments
 Pigments include
 Chlorophyll
 Found in plants, algae and cyanobacteria

Bacteriochlorophylls
 Found in purple and green photosynthetic bacteria

Accessory pigments
 Includes carotenoids and phycobilins
 Carotenoids found in eukaryotes and prokaryotes
 Phycobilins found only in cyanobacteria

Reaction center pigments
 Function as electron donors

Antennae pigments
 Funnels light energy to reaction center pigments
Photosynthesis
 Converting radiant energy to chemical energy

Light reactions accomplish two tasks


Synthesize ATP through photophosphorylation
Generate reducing power to fix carbon dioxide
 Reducing power may be NADH or NADPH
Light Dependant Reactions
Carbon Fixation
 Carbon dioxide converted to organic carbon
through carbon fixation



Occurs in dark reactions in photosynthesis
Consumes great deal of energy
Calvin cycle most common pathway of carbon
fixation
Carbon fixation
 Calvin Cycle


A.k.a Calvin-Benson
cycle
Has three essential
stages




One molecule of fructose
produces from 6 turns of
cycle


Incorporation of CO2
into organic compound
Reduction of resulting
molecules
Regeneration of
starting compound
6 turns consumes 18
ATP and 12 NADPH
Process has three sages
Anabolic Pathways
 Synthesis of subunits from precursor
metabolites


Pathways consume ATP, reducing power and
precursor metabolites
Macromolecules produces once subunits are
synthesized
Anabolic Pathways
 Lipid synthesis

Synthesis begins with transfer of acetyl group
from acetyl CoA to acyl carrier protein

Carrier hold fatty acid during elongation
 Fatty acid released when reaches required length
 14, 16 or 18 carbons long

Glycerol is synthesized from dihydroxyacetone
phosphate
Anabolic Pathways
 Amino acid synthesis
 Some precursors are formed in glycolysis
other in TCA cycle
 Glutamate synthesis essential for formation of
other amino acids

Synthesis incorporates ammonia with αketoglutarate produce in TCA cycle
 Amino group from glutamate can be transferred to
produced other amino acids

Precursors for aromatic amino acids produced
in pentose phosphate pathway and glycolysis
Anabolic Pathways
 Nucleotide synthesis

Nucleotides synthesized as ribonucleotides
and modified to deoxribonucleotides

Replace OH group on 2’ carbon of ribose and
replace with hydrogen atom
 Remove oxygen