Metabolism: Fueling Cell Growth
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Transcript of Metabolism: Fueling Cell Growth
Metabolism:Fueling Cell Growth
Chapter 6
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• Principles of metabolism– Metabolism, catabolism, anabolism, energy,
redox reaction….
• Central metabolic pathway– Glycolysis, TCA
• Respiration– Electron transport chain
• Fermentation
Metabolism
• Chemical reactions to keep an organism alive.
• Basic needs
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
Metabolic Pathways
Principles of Metabolism
Glycolysis TCA Cycle
Energy
• Definition• Free energy-energy released
by breaking chemical bonds– reactants have more free energy
• Exergonic reaction
– products have more energy• Endergonic reaction
Energy source– Compound broken down to
release energy– Common energy sources
Energy
• Oxidizing energy source to release energy
Gas +O2 CO2+H2O+energy
Glucose+O2 CO2 +H2O +energy
Oxidization: gain of oxygen, loss of hydrogen, loss of electron
Harvesting Energy
•Oxidation/reduction reactions (redox reactions)
LEO - Lose electrons oxidizedGER - Gain electrons reduced
electron donor electron acceptor
Protons often follow electrons (i.e. a hydrogen atom is extracted/added; e- + H+ = H )General rules:
•If a compound gains oxygen or loses hydrogen, the reaction is an oxidation•If a compound loses oxygen or gains hydrogen, the reaction is a reduction
Harvesting Energy
The role of electron carriers
“reducing power”
In redox reactions, protons often follow electrons
Harvesting Energy
energy currency
Adenosine triphosphate
The role of ATP
Harvesting Energy
energy currencyThe role of ATP
Harvesting Energy
Synthesizing ATP•Substrate-level phosphorylation
Harvesting Energy
Synthesizing ATP•Substrate-level phosphorylation
•Other methods involve an electron transport chain and redox reaction
•Oxidative phosphorylation•Photophosphorylation
Principles of Metabolism
Synthesizing ATP•Substrate-level phosphorylation•Oxidative phosphorylation - chemical energy is used to create the proton motive force (involves an electron transport chain); the energy of proton motive force is harvested by making ATP;
•Photophosphorylation - radiant energy is used to create the proton motive force (involves an electron transport chain); the energy of proton motive force is harvested by making ATP
Central pathways are catabolic and provide
• Energy• Reducing power• Precursor metabolites
• Central metabolic pathways
• Glycolysis• Pentose phosphate pathway• Tricarboxcylic acid cycle
Central metabolic pathway
Central Metabolic PathwaysGlycolysis (aka Embden-Meyerhoff pathway, glycolytic pathway)
glucose 2 pyruvate
Central Metabolic PathwaysGlycolysis (aka Embden-Meyerhoff pathway, glycolytic pathway)
glucose 2 pyruvate •2 ATP (net gain)
•2 spent; 4 made •2 NADH•6 precursor metabolites
Central Metabolic PathwaysGlycolysis (aka Embden-Meyerhoff pathway, glycolytic pathway)
glucose 2 pyruvate •2 ATP (net gain)
•2 spent; 4 made •2 NADH•6 precursor metabolites
Central Metabolic PathwaysGlycolysis (aka Embden-Meyerhoff pathway, glycolytic pathway)
glucose 2 pyruvate •2 ATP (net gain)
•2 spent; 4 made•2 NADH•6 precursor metabolites
Central Metabolic Pathways
glucose intermediate of glycolysis
•NADPH (amount varies)•2 precursor metabolites
Pentose phosphate pathway
Central Metabolic Pathways
•NADPH (amount varies)•2 precursor metabolites
Primary role is biosynthesis; ignored in energy-yield calculations;
glucose intermediate of glycolysis
Pentose phosphate pathway
Central Metabolic Pathways
•NADPH (amount varies)•2 precursor metabolites
glucose intermediate of glycolysis
Pentose phosphate pathway
Primary role is biosynthesis; ignored in energy-yield calculations;
Central Metabolic Pathways
pyruvate (3 C) acetyl CoA (2 C) + CO2
(twice per glucose)
Transition step
Central Metabolic PathwaysTransition step
pyruvate (3 C) acetyl CoA (2 C) + CO2
(twice per glucose)•NADH•precursor metabolite
Central Metabolic Pathways
acetyl CoA (2 C) 2 CO2
(twice per glucose)
TCA cycle (aka Kreb’s cycle, citric acid cycle)
Central Metabolic Pathways
acetyl CoA (2 C) 2 CO2
(twice per glucose)
•3 NADH•FADH2
•2 precursor metabolites
•ATP
TCA cycle (aka Kreb’s cycle, citric acid cycle)
Central Metabolic Pathways
acetyl CoA (2 C) 2 CO2
(twice per glucose)
TCA cycle (aka Kreb’s cycle, citric acid cycle)
•3 NADH•FADH2
•2 precursor metabolites
•ATP
Central Metabolic Pathways
acetyl CoA (2 C) 2 CO2
(twice per glucose)
TCA cycle (aka Kreb’s cycle, citric acid cycle)
•3 NADH•FADH2
•2 precursor metabolites
•ATP
Review of central metabolic pathway
ATP (substrate-level phosphorylation)
Glucose (C6H12O6)
6 CO2
Precursor metabolites
BiosynthesisElectron transport chain
ATP (oxidative phosphorylation)
- carried by NADH, FADH2, NADPH
GlycolysisPentose phosphate pathwayKreb’s cycle (+ transition step)
Electrons (protons often follow, therefore H atoms removed)
Oxidation of glucose= Dehydrogenation to CO2+ reducing power (H)
Precursor Metabolites
Intermediates of catabolism also used in biosynthesis
Review
Respiration
Electron Transport Chainof mitochondria
Part of figure 3.53
TCA cycleElectron carrier get recycledElectron transport chainOxidative phosphorylation
Electron Transport Chainof mitochondria
Terminal electron acceptorFADH2 FAD
Inside of mitochondria
Electron Transport Chainof mitochondria
Creates the proton motive force
FADH2 FAD
Electron Transport Chainof mitochondria
FADH2 FAD
Electron Transport ChainThe Mechanics
Electron Transport Chain
Hydrogen carrier
Electron carrier
Electron carrier
Hydrogen carrier
Electron carrier2H+
2H+
Hydrogen carrier
2e- 2H+
NADH + H+
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chain
Hydrogen carrier
Electron carrier
Electron carrier
Hydrogen carrier
Electron carrier2H+
2H+
Hydrogen carrier
NAD
2e- 2H+
Mitochondrial matrix(outside)(inside)
Intermembrane space
Regenerates NAD
Electron Transport Chain
Hydrogen carrier
Electron carrier
Electron carrier
Hydrogen carrier
Electron carrier
2e-
2H+
2H+
Hydrogen carrier
2H+
NAD
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chain
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
2e-
2H+
2H+
2H+
NAD
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chain
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
2H+
2e-
2H+
NAD
2H+
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chain
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
2H+
2e- 2H+
NAD
2H+
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chain
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
Hydrogen carrier
Electron carrier
2H+
2e-
2H+
NAD
2H+
Terminal electron acceptor
Mitochondrial matrix(outside)(inside)
Intermembrane space
Electron Transport Chainof mitochondria
FADH2 FAD
Electron Transport Chainof E. coli
Aerobic respiration (shown)Anaerobic respiration
•NO3 as a TEA (different ubiquinol oxidase)•Quinone used provides humans with vitamin K
FADH2 FAD
Harvesting Energy
12 pairs of electrons (snatched by electron carriers)
•Passed to the electron transport chain (used to create the proton motive force); ultimately passed to a terminal electron acceptor (such as O2, making H2O)
•Used in biosynthesis (to reduce compounds)
The role of electron carriers
C6H12O6 + 6 O2 6 CO2 + 6 H2O
e- O2 H2O
Principles of Metabolism
Synthesizing ATP
ATPsynthase
•Substrate-level phosphorylation•Oxidative phosphorylation - the energy of proton motive force is harvested; chemical energy is used to create the proton motive force (involves an electron transport chain)
ADP + Pi ATPe- O2 H2O
Harvesting Energy
Energy source versus terminal electron acceptor
Glucose + 6 O2 6 CO2 + 12 H2O
Overall Maximum Energy Yield
Complete oxidation of glucose4 ATP
Overall maximum energy yield of aerobic respiration (ignoring the pentose phosphate pathway):
10 NADH2 FADH2
Electron transport chain (oxidative phosphorylation)
•3 ATP/NADH•2 ATP/FADH2
Overall Maximum Energy Yield
Complete oxidation of glucose4 ATP
Electron transport chain (oxidative phosphorylation)
Overall maximum energy yield of aerobic respiration (ignoring the pentose phosphate pathway):
•3 ATP/NADH•2 ATP/FADH2
10 NADH2 FADH2
38 ATP (maximum theoretical)
Respiration
Fermentation•Used when respiration is not an option
•Lack of TEA•No electron transport chain
•Oxidation of glucose stops at pyruvate
NAD NADH
The logic:•Oxidizes NADH, generating NAD for use in further rounds of glucose breakdown•Stops short of the transition step and the TCA cycle, which together generate 5X more reducing power
•Passes electrons from NADH to pyruvate or a derivative
Fermentation
Fermentation
Review
Catabolism of Organic Compounds Other than Glucose (The Elegance of Metabolism)
Anabolic Pathways
• Synthesis of subunits from precursor metabolites– Pathways consume ATP, reducing power and
precursor metabolites– Macromolecules produces once subunits are
synthesized
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
Enzymes
•A specific, unique, enzyme catalyzes each biochemical reaction
•Enzyme activity can be controlled by a cell
•Enzymes can be exploited medically, industrially
•Enzyme names usually reflect the function and end in -ase
Enzymes
EnzymesAllosteric regulation
reversible
EnzymesEnzyme inhibition
Competitive inhibition
Ex.: PABA folic acid coenzyme
- Inhibitor/substrate act at the same site
Sulfa
EnzymesEnzyme inhibition
Non-competitive inhibition•Regulation (allosteric)•Enzyme poisons (example: mercury)
- Inhibitor/substrate act at different sites
EnzymesEnvironmental factors influence enzyme activity
temperature, pH
Enzymes
Coenzymes are organic cofactors
Cofactors act in conjunction with certain enzymes