metabolism: fueling cell growth

Metabolism:Fueling Cell Growth

Chapter 6

Preview

• 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