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Definition of Respiration

• Respiration– process that occurs in cells – breakdown food molecules– yield ATP.

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Types of respiration

• Aerobic Respiration– A metabolic process involving oxygen in

the breakdown of glucose

• Anaerobic Respiration– A metabolic process that does not

involve oxygen in the breakdown of glucose.

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AEROBIC RESPIRATION

There are four main stages which are locate in difference places :

1. Glycolysis• in the cytosol.

2. The link reaction (pyruvate oxidation)• in the matrix of the mitochondria.

3. The Krebs cycle• within the mitochondrial matrix.

4. Electron transport systems • in inner membranes of mitochondria/cristae

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Glycolysis

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Glycolysis

• Glucose is phosphorylated, receives a high energy phosphate from ATP to increase its energy level to become glucose-6-phosphate, more reactive.

• Glucose-6-phosphate is rearranged to become fructose-6-phosphate.

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• Fructose-6-phosphate is activated by the addition of phosphate from ATP to form fructose-1,6-diphosphate.

• Fructose-1,6-diphosphate is split into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

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• Glyceraldehyde-3-phosphate is oxidised, H atoms are removed, NAD+ is reduced to become NADH.

• It produced 1,3-biphosphoglycerate.

• 1 phosphate from 1,3-biphosphate is transferred to ADP to form ATP.

• It produced 3-phosphoglycerate

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• 3-phosphoglycerate is rearranged to form 2-phosphoglycerate.

• Removal of water produces phosphoenolpyruvate.

• Phosphate is transferred to ADP to form ATP.

• Phosphoenolpyruvate is converted to pyruvate.

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The Link Reaction

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The Link Reaction(pyruvate oxidation)

• Occurs in the matrix of the mitochondria• Links glycolysis with the Krebs cycle.

During the link reaction the 1. Pyruvate combines with coenzyme A to form acetyl coenzyme A.2. One molecule of carbon dioxide and hydrogen atom are

removed forming acetyl (2C).3. Acetyl (2C) and coenzyme A will associate, forming acetyl CoA

which will then enter the Krebs cycle.

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Cellular respiration(summary)

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Krebs Cycle

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Hydrogen carrier

•NAD

•Nicotinamide adenine dinucleotide

•FAD

•Flavine adenine dinucleotide

•FMN

•Flavin mononucleotide

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1. Acetyl (2C) is transferred from acetyl-CoA to oxaloacetate (4C) forming citrate (6C).

2. Citrate (6C) was rearranged to form isocitrate(6C).

3. Isocitrate (6C) is oxidized and decarboxylated to form α-ketoglutarate (5C).

4. α-ketoglutarate (5C) is oxidized and decarboxylated forming succinyl CoA (4C) by adding CoA.

Krebs Cycle

Oxidized

*hydrogen atom removed to from NADH or FADH2

Decarboxylated

*carbon removed to form CO2

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5. CoA was released from succinyl CoA (4C) forming succinate (4C) and generates one molecule of ATP.

6. Succinate (4C) is oxidized to form fumarate (4C).

7. Fumarate (4C) was changed to malate (4C) by adding one molecule of water.

8. Finally, malate (4C) is oxidized. This regenerates oxaloacetate (4C) (starting material), completing the cycle.

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Cellular respiration(summary)

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Electron Transport Chain

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Electron Transport Chain1. A collection of molecules (mostly proteins) embedded in the

inner membrane of mitochondria.

2. Folding of the inner membrane into cristae increases surface area of inner membrane (increases the number of electron transport chains).

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Electron Transport ChainThe flow of ETC :

i. The hydrogen atoms removed from glycolysis and the Krebs cycle are transferred to specific carriers of the electron transport chain on the inner membrane of mitochondria by NADH and FADH2.

ii. The hydrogen are passed along carriers and then split into their protons (H+) and electrons along the chain.

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iii. The chain consist of 3 protein complexes;a) NADH dehydrogenase complex

b) Cytochrome b complex

c) Cytochrome oxidase complex and 2 mobile carriers;i. Ubiquinone (Q)

ii. Cytochrome c (cyt c)

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iv. Ubiquinone (Q) and cytochrome c (Cyt c) move rapidly (carrying electrons) along the mitochondria membrane between the 3 complexes.

v. Electrons are passed from one carrier to another.

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vi. The carrier molecule gaining an electron is reduced and the carrier molecule losing the electron is oxidised and able to accept more electrons.

vii. Energy released from passing electrons down the chain are used to pump H+ out of the matrix into intermembrane space.

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viii. Now, there is a greater concentration of H+ outside of the matrix.

ix. H+ flow back into the matrix through the channels in ATP synthase molecules in the membrane.

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x. The energy released as H+ flow back into the ATP synthase channel are then used to phosphorilate ADP into ATP.

xi. The above process is called oxidative phosphorylation because phosphorylation occurs from energy associated with the transfer of electrons from food to oxygen.

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xii. The final electron aceptor at the end of the chain is O2 which combines with H+ to form H2O

Chemiosmosis– the use of H+ gradient to transfer energy from redox reactions to

work (phosphorylation of ATP).

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Cellular respiration(summary)

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Cellular respiration(summary)

Aspects Glicolysis Link reactions Krebs cycle

Electron transport

chain

Location Cytoplasm

Matrix of mitochondia

Matrix of mitochondia

Inner membrane of mito chondrion

Products

2 NADH

2 ATP

2 pyruvate

2 NADH

6 NADH

2 FADH2

2 ATP

32 ATP

Or

34 ATP

Net ATP 2 ATP 2 ATP

32 ATP

Or

34 ATP

Reactions C6 H12 O6 + 6 O2 → 6 CO2 + 6 H20 + 36 or 38 ATP

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ATP Production in aerobic respiration

• When electrons flow through the ETC, a proton gradient is generated and– ATP is produced by chemiosmosis– 1 NADH can generate 3 ATP– 1 FADH2 can generate 2 ATP

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• Glycolysis– 2 ATP– 2 NADH (will enter ETC)

• Link reaction– 2 NADH (will enter ETC)

• Krebs cycle– 2 ATP– 6 NADH (will enter ETC)– 2 FADH2 (will enter ETC)

• Electron Transport Chain (ETC)– 2 NADH (glycolysis) = 2 X 3 ATP = 6 ATP– 2 NADH (link reaction) = 2 X 3 ATP = 6 ATP– 6 NADH (Krebs cycle) = 6 X 3 ATP = 18 ATP– 2 FADH2 (Krebs cycle) = 2 X 2 ATP = 4 ATP

Number of ATP produced in ETC = 34 ATP

TOTAL ATP= 34 +2 + 2 = 38 ATP

ATP Production in aerobic respiration

(active cells or in heart muscle )

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• Glycolysis– 2 ATP– 2 NADH (will enter ETC)

• Link reaction– 2 NADH (will enter ETC)

• Krebs cycle– 2 ATP– 6 NADH (will enter ETC)– 2 FADH2 (will enter ETC)

• Electron Transport Chain (ETC)– 2 NADH (glycolysis) = 2 X 2 ATP = 4 ATP– 2 NADH (link reaction) = 2 X 3 ATP = 6 ATP– 6 NADH (Krebs cycle) = 6 X 3 ATP = 18 ATP– 2 FADH2 (Krebs cycle) = 2 X 2 ATP = 4 ATP

Number of ATP produced in ETC = 32 ATP

TOTAL ATP= 32 +2 + 2 = 36 ATP

ATP Production in aerobic respiration(ordinary cells)

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Shuttle

• In most cells, ATP yield is lower from an NADH produced during glycolysis.

• Mitochondrial membrane is impermeable to NADH.– Its electrons must be carried across the membrane by

one of the several shuttle mechanism.

– Shuttle mechanisms transport metabolites between mitochondria and cytosol.

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Shuttle

1. Glycerol phosphate shuttle– Found in most cells

– 2 ATP are produced in mitochondria for each cystolic NADH

2. Malate-Aspartate shuttle– Found in mamalian kidney, liver, and heart

– 3 ATP are produced in mitochondria for each cystolic NADH

Shuttle

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Malate-Aspartate Shuttle(active cells)

Cytoplasm

Matrik of mitochondrion

Oxaloacetate

Oxaloacetate

Malate

Malate

NADH

NAD+

NAD+

NADH

(from glycolysis)

(to ETC)

α-ketoglutarate

Glutamate

Aspartate

Aspartate α-ketoglutarateGlutamate

Inner membrane

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Glycerol phosphate shuttle(ordinary cells)

Cytoplasm

Matrix of mitochondrion

Dihydroxyacetone phosphate

Dihdroxyacetone phosphate

Glycerol phosphate

Glycerol phosphate

NADH NAD+

FAD+FADH2

(from glycolysis)

(to ETC)

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ATP(adenosine triphosphate)

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• The immediate source of energy that powers cellular work is ATP.

• ATP is a type of nucleotide consisting– nitrogenous base adenine

– sugar ribose

– three phosphate groups.

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• The bonds between phosphate groups can be broken by hydrolysis.– Hydrolysis of the end phosphate group forms

adenosine diphosphate (ADP)

ATP ADP + Pi

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• Phosphate bonds of ATP are referred to high-energy phosphate bonds, these are actually fairly weak covalent bonds.

• They are unstable however and their hydrolysis yields energy as the products are more stable.

• The phosphate bonds are weak because each of the three phosphate groups has a negative charge.

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• In the cell the energy from the hydrolysis of ATP is coupled directly to endergonic processes by transferring the phosphate group to another molecule.– This molecule is now phosphorylated.– This molecule is now more reactive.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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• ATP is a renewable resource that is continually regenerated by adding a phosphate group to ADP.– The energy to support renewal comes from catabolic

reactions in the cell.

• Regeneration, an endergonic process, requires an investment of energy.

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ANAEROBIC RESPIRATION

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ANAEROBIC RESPIRATION

Anaerobic Respiration

• A metabolic process that does not involve oxygen in the breakdown of glucose.

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Fermentation– Anaerobic respiration is generation of ATP from

glucose in absence of O2

– In fermentation, glucose only goes through the steps of Glycolysis

– 2 Pyruvates that are formed does not enter krebs cycle or electron transport chain

– THUS, only 2 ATP are produced per molecule of glucose

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Importance of fermentation in industryAlcohol Fermentation

• In alcohol fermentation, pyruvate is converted to ethanol in two steps.

– First, pyruvate is converted to a two-carbon compound, acetaldehyde by the removal of CO2.

– Second, acetaldehyde is reduced by NADH to ethanol.– Alcohol fermentation by yeast is used in brewing and

winemaking.

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Lactic acid fermentation• During lactic acid fermentation, pyruvate is reduced

directly by NADH to form lactate (ionized form of lactic acid).

• no release of CO2 • carried out by human muscle cells when O2 is depleted;

accumulation of lactate in muscle causes pain/fatigue

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– Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt.

– Muscle cells switch from aerobic respiration to lactic acid fermentation to generate ATP when O2 is scarce.

• The waste product, lactate, may cause muscle fatigue, but ultimately it is converted back to pyruvate in the liver.

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Alternative sources of energy

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• Glycolysis can accept a wide range of carbohydrates.

– Polysaccharides, like starch or glycogen, can be hydrolyzed to glucose monomers that enter glycolysis.

– Other hexose sugars, like galactose and fructose, can also be modified to undergo glycolysis.

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• The other two major fuels, proteins and fats, can also enter the respiratory pathways, including glycolysis and the Krebs cycle, used by carbohydrates.

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Carbohydrate Blood glucose Glucose-6-phosphate

(Tissue and liver)

Glucose-1-phosphate

Glycogen

(Liver)

Glycogen (Muscle)

Pyruvate

aerobicanaerobic

Lactate + energy CO2 + H2O + energy

Amino acid Glycerol, fatty acid

digestion insulinglycogenesis

glycogenolysisGluconeogenesis

Carbohydrate, Fats, and Proteins Metabolism

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Fats (lipid) metabolism

• Fats in the liver can be modified for respiration and can be stored in the body cells

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Fats • The energy of fats can also be

accessed via catabolic pathways.

• Fats must be digested to glycerol and fatty acids.

– Glycerol can be converted to glyceraldehyde phosphate, an intermediate of glycolysis.

– The rich energy of fatty acids is accessed as fatty acids are split into two-carbon fragments via beta oxidation.

– These molecules enter the Krebs cycle as acetyl CoA.

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Carbohydrate Blood glucose Glucose-6-phosphate

(Tissue and liver)

Glucose-1-phosphate

Glycogen

(Liver)

Glycogen (Muscle)

Pyruvate

aerobicanaerobic

Lactate + energy CO2 + H2O + energy

Amino acid Glycerol, fatty acid

digestion insulinglycogenesis

glycogenolysisGluconeogenesis

Carbohydrate, Fats, and Proteins Metabolism

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Fats

• In fact, a gram of fat will generate twice as much ATP as a gram of carbohydrate via aerobic respiration.

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Protein Metabolism

• Protein being recycled are first broken down into amino acids.

• Hepatocytes (liver cells) convert amino acids to fatty acid, ketone bodies, glucose or oxidize them to carbon dioxide and water

• There are two ways of protein metabolism– Deamination

• a conversion consists of removing the amino group from the amino acids and converting it to ammonia

– Transamination• the transfer of an amino group from an amino acid to pyruvic acid or to

an acid in the Krebs cycle-can synthesized nonessential amino acids

• Ornithine Cycle shows the formation of urea

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Metabolism of excess amino acid

Excess amino acid

Keto acid + NH3

Glucose

Glycogen Fats

Krebs cycle

Ornithine cycle

deamination

H2O + CO2 urea

CO2

Production of organic base

Nucleotide synthesis

Nucleic acid synthesis

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Ornithine cycle (urea cycle)

citruline

arginosuccinate

arginine

ornithine

H2O

urea

Carbamoyl phosphate

Pi

aspartate

NH3

ATP

AMP + PPi

fumarate

Deamination of amino acid

NH3 + CO2 + H2O

2 ATP

2 ADP + Pi

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• Carbohydrates, fats, and proteins can all be catabolized through the same pathways.

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The needs for energy and the role of respiration in living organism

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Metabolic reaction (metabolism)

• Biochemical reactions that occur in living organisms

• Metabolic reaction

1. Anabolic reaction (anabolism)• Anabolic pathways consume energy to build complicated

molecules from simpler compounds

2. Catabolic reaction (catabolism)• Catabolic pathways release energy by breaking down

complex molecules to simpler compounds.

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The importance of ATP

ATP provides the energy for :• Substrate level phosphorylation• Chemiosmosis• Muscle contraction• Urea synthesis• Protein synthesis• Active transport systems• Calvin cycle (dark stage of photosynthesis) • Nitrogen fixation

– involves the ATP-driven reduction of molecular nitrogen

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• A cell does three main kinds of work:– Mechanical work

• beating of cilia, contraction of muscle cells, and movement of chromosomes

– Transport work• pumping substances across membranes against the direction of

spontaneous movement

– Chemical work• driving endergonic reactions such as the synthesis of polymers

from monomers.

• In most cases, the immediate source of energy that powers cellular work is ATP.

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That’s all for this topic

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QUESTIONS

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Final exam 2005/2006

Question number : 6

• Describe how one molecule of glucose is able to produce 36 ATP via aerobic respiration.

[14 marks]

• Explain the production of lactic acid during anaerobic respiration.

[6 marks]

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Final exam 2004/2005

Question number : 6

a) Compare between aerobic and anaerobic respirations.

[8 marks]

b) Describe the stages in the production of NAD and its role in cellular respiration.

[12 marks]

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Final exam (January intake) 1999/2000

Question number : 3

a) Describe the structure of ATP and its functions in cellular metabolism.

[6 marks]

b) Aerobic respiration produced more ATP compared to anaerobic respiration. Explain this statement. [14 marks]

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Final exam (Jun intake) 1999/2000

Question number : 4

Glucose undergo three phase of oxidation

during cellular respiration

i. Glycolysis

ii. Krebs cycle

iii. Oxidative phosphorylation

Complete the table below with suitable answer.

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Aspect Glycolysis Krebs cycle Oxidative phosphorylation

1. Location Cytoplasm (i) (ii)

2. Products Two main products

(iii)

(iv)

Two main products

(v)

(vi)

Two main products

ATP

Water

3. Net amount of ATP (vii) 2 (viii)

4. Equation for cellular respiration

(ix)(ix)