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1 Cellular Energy: Respiration Aerobic respiration Goals: Define and describe the 3 sets of chemical reactions that comprise aerobic cellular respiration Describe the 2 types of anaerobic respiration Compare anaerobic and aerobic cellular respiration Use knowledge of cellular respiration to solve problems related to human health and disease Aerobic cellular respiration occurs in 3 stages 1- Glycolysis. 2- Citric acid cycle. 3- Oxidative phosphorylation.

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Cellular Energy: Respiration

Aerobic respiration

Goals:• Define and describe the 3 sets of chemical

reactions that comprise aerobic cellular respiration

• Describe the 2 types of anaerobic respiration

• Compare anaerobic and aerobic cellular respiration

• Use knowledge of cellular respiration to solve problems related to human health and disease

Aerobic cellular respiration occurs in 3 stages

1- Glycolysis.

2- Citric acid cycle.

3- Oxidative phosphorylation.

2

ReactantsGlucose, 2 ADP, 2 P, 2 NAD+

Products2 ATP, 2 NADH+H, 2 Pyruvate

ATP is formed by ________________________.

NAD+ is __________to NADH.

Review Stage 1: Glycolysis Glucose

NAD+

+2

2 ADP

NADH2

P2

2

ATP2 +

H+

2 Pyruvate

Substrate level phosphorylation

REDUCED

2 ATP

4 ADP

4

4

INITIAL INVESTMENT = 2 ATP

TOTAL ATP PRODUCED = 4 ATPNET ATP PRODUCED = 2 ATP

Review Anaerobic Respiration

• _________

or __________ fermentation

• NADH+H from

glycolysis is __________ back to

NAD+

Glucose

NADH

NAD+

2

2

NADH2

NAD+2

2 ADP

P

ATP2

2 Pyruvate

2 Lactate

GL

YC

OL

YS

IS

++++ 22 ADP

P

ATP2 GL

YC

OL

YS

IS

NADH

NAD+

2

2

NADH2

NAD+2

2 Pyruvate

2 Ethanol

Glucose

CO22

released

++++ 2

LACTIC ACID

ALCOHOLIC

OXIDIZED

The citric acid cycle completes the

oxidation of glucose in aerobic

cellular respiration

3

Stage 2: Citric acid cycle

A set of 5 enzyme-driven chemical reactions, collectively called a metabolic pathway.

Occurs in the mitochondria (within the matrix and inner membrane).

Does not use oxygen.

The net molecular products of the citric acid cycle for 1 glucose molecule are:

- 4 CO2

- 6 NADH- 2 FADH- 2 ATP

• The pyruvate molecules produced by glycolysis are modified after being transported into the mitochondria.

- One carbon is removed as CO2

- One electron is removed when NAD+ is reduced to NADH

- The compound coenzyme A is added to make acetyl coenzyme A (acetyl CoA)

2 made per original glucose

Pyruvate from glycolysis is first “groomed”

• Two carbons (acetyl) are carried to the start of the cycle by coenzyme A

• 2 CO2, 1 FADH2, and 1 ATP exit the cycle

How many pyruvates (and therefore acetyle CoA’s) per glucose?

2!

Stage 2: The Citric

Acid Cycle

4

CITRIC ACID CYCLE

CoA

2 carbons enter cycle

Acetyl CoA

CoA

1Oxaloacetate

1Step

Acetyl CoA stokes the furnace.

Stage 2: The Citric Acid Cycle

CITRIC ACID CYCLE

CoA

2 carbons enter cycle

Acetyl CoA

CoA

1Oxaloacetate

1Step

Acetyl CoA stokes the furnace.

2

3

NAD+

NADH

CO2

Citrate

ADP +

+ H+

P

Alpha-ketoglutarate

leaves cycle

ATP

NAD+NADH

CO2

+ H+

leaves cycle

Steps –

NADH, ATP, and CO2 are generated

during redox reactions.

2 3

Stage 2: The Citric Acid Cycle

CITRIC ACID CYCLE

CoA

2 carbons enter cycle

Acetyl CoA

CoA

1Oxaloacetate

1Step

Acetyl CoA stokes the furnace.

2

3

NADH

CO2

Citrate

ADP ++++ P

Alpha-ketoglutarate

leaves cycle

ATP

NADH

CO2 leaves cycle

Steps –

NADH, ATP, and CO2 are generated

during redox reactions.

2 3

5NAD+

NADH

Malate

+ H+

4FADH2

FAD

Succinate

Steps –

Redox reactions generate FADH2

and NADH.

4 5

NAD+

+ H+

NAD++ H+

Stage 2: The Citric Acid Cycle

5

Lactic Acid Fermentation Alcoholic Fermentation

2 NADH 2 NAD+

2 Pyruvate 2 Lactate

2 NADH 2 NAD+

2 Pyruvate 2 Ethanol + 2 CO2

OR

Stage 3: Oxidative phosphorylationProduces lots of ATP (about 32) by capturing the energy from electron carriers (NADH and FADH2) generated in the first two steps of cellular respiration.

Occurs in the mitochondria (across the inner membrane and in the intermembranespace)

Involves the electron transport chain and chemiosmosis

Transfers electrons to the “terminal electron acceptor”oxygen.

Intermembranespace

ATP

H+

Intermembranespace

O2

H2O

1−−−−2

Innermitochondrialmembrane

H+NAD+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

Mitochondrialmatrix

Electronflow

Electroncarrier

Proteincomplexof electroncarriers

NADH

FADH2 FAD

ATPsynthase

PADP +

Chemiosmosis

+ 2

OXIDATIVE PHOSPHORYLATION

Electron Transport Chain

6

Stage 3a: The electron transport chain

• The e-s associated with the coenzymes NADH and FADH2 have a lot of potential energy .

• They give up small bits of their potential energy to protein complexes in the inner mitochondrial membrane.

Electrons from glucose fall down an “energy staircase”

ATPNAD+

NADH

H+

H+2e–

2e–

Electron transport

chain

Controlledrelease ofenergy forsynthesis

of ATP

+

O2

H2O

1−−−−2

Stage 3a: The electron transport chain

• The e-s associated with the coenzymes NADH and FADH2 have a lot of potential energy .

• They give up small bits of their potential energy to protein complexes in the inner mitochondrial membrane.

• Some of these complexes use this energy to pump H+ ions across the membrane into the intermembrane space against their concentration gradient.

• e-s are transferred from membrane protein to membrane protein, giving up some of their energy with each transfer .

7

• The final e- acceptor molecule is oxygen .- Each molecule of O2 picks up 2 H+ to form H2O.

Stage 3a: The electron transport chain

• Without oxygen at the end to “pull” the e-s down the transport chain the earlier steps do not occur i.e. no H+ ion gradient is formed across the membrane.

Stage 3b: ATP synthase

• Enzyme complexes in the inner membrane called ATP synthases use the potential energy of the H+ ion gradient to phosphorylate ADP to ATP.

• H+ ions flow through a channel in the ATP synthaseprotein complex and, which energize it to produce ATP. This is called chemiosmosis.

Lactic Acid Fermentation Alcoholic Fermentation

2 NADH 2 NAD+

2 Pyruvate 2 Lactate

2 NADH 2 NAD+

2 Pyruvate 2 Ethanol + 2 CO2

OR

8

Which type of skeletal muscle fibers will have more mitochondria?• Slow Twitch (Type I)

The slow muscles are more efficient at using oxygen to generate more fuel (known as ATP) for continuous, extended muscle contractions over a long time. They fire more slowly than fast twitch fibers and can go for a long time before they fatigue. Therefore, slow twitch fibers are great at helping athletes run marathons and bicycle for hours.

• Fast Twitch (Type II)Because fast twitch fibers use anaerobic metabolism to create fuel, they are much better at generating short bursts of strength or speed than slow muscles. However, they fatigue more quickly. Fast twitch fibers generally produce the same amount of force per contraction as slow muscles, but they get their name because they are able to fire more rapidly. Having more fast twitch fibers can be an asset to a sprinter since she needs to quickly generate a lot of force.

Diagram the pathway that produces and

then breaks down lactic acid“… the working muscles generate energy anaerobically. This energy comes from glucose through a process called glycolysis, in which glucose is broken down or metabolized into a substance called pyruvate through a series of steps. When the body has plenty of oxygen, pyruvate is shuttled to an aerobic pathway to be further broken down for more energy. But when oxygen is limited, the body temporarily converts pyruvate into a substance called lactate, which allows glucose breakdown--and thus energy production--to continue. The working muscle cells can continue this type of anaerobic energy production at high rates for one to three minutes, during which time lactate can accumulate to high levels…. Once the body slows down, oxygen becomes available and lactate reverts back to pyruvate, allowing continued aerobic metabolism and energy for the body’s recovery from the strenuous event. … Lactic acid is actually a fuel, not a caustic waste product. Muscles make it deliberately, producing it from glucose, and they burn it to obtain energy. The reason trained athletes can perform so hard and so long is because their intense training causes their muscles to adapt so they more readily and efficiently absorb lactic acid.”

Cells can use other organic moleculesas fuel for cellular respiration.

9

Food, such aspeanuts!

ProteinsFatsCarbohydrates

Glucose

OXIDATIVEPHOSPHORYLATION(Electron Transportand Chemiosmosis)

CITRICACID

CYCLE

AcetylCoA

GLYCOLYSIS

Pyruvate

Amino acidsGlycerolSugars Fatty acids

Amino groups

G3P

ATP

Organic molecules also provide rawmaterials for biosynthesis.

Cells, tissues, organisms

Proteins Fats Carbohydrates

GlucoseCITRICACID

CYCLE

AcetylCoA

GLUCOSE SYNTHESIS

Pyruvate

Amino acids Glycerol SugarsFatty acids

Amino groups

G3P

Uses ATP!

Biosynthesis of raw materials from food molecules

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“Supply and demand” regulation

� Cellular respiration: If ATP accumulates in a cell to highlevels, the excess ATP will inhibit glycolysis, slowing down respiration, and thus conserving resources.

� This type of regulation is called feedback inhibition.

� Feedback inhibition also regulates biosynthesis.

Cellular RespirationA Case Study

The Case

• You’re working at the medical examiner’s office at San Francisco County Hospital. It has been a particularly light day. Just as you’re flipping the switch, you get a call from your secretary. “Francesca,” he says. “We’ve got a dead kid up here that you’ll want to look at right away. Might be foul play.”

• Thinking of your four-year old daughter waiting for you at home, you grimace. “OK Jon, I’m heading to the morgue.” Performing autopsies on kids is the least favorite part of your job. But you are paid to solve medical mysteries, and it looks like you’ve got one here.

11

• In the morgue, you find the report from the hospital. Glancing over it, you notice a narrative of the girl’s last hours and read it carefully:– At 10 AM, mother returns from the store to find girl

vomiting, not feeling well, and sleepy. Mother put girl to bed. Ten minutes later, she noticed that the child’s breathing became irregular and slow. She tried to wake her daughter but was not able to do so. The child became comatose. At noon, the girl was admitted to the hospital, with no heartbeat or spontaneous breathing.

• A police report states the following:– The parents discovered that the girl had been giving

her dog a bath using a flea dip called Fleacide. According to the label on the container, Fleacide is an insecticide made of plant material only and appropriate for external use on animals.

The Case II

New

&

Impro

ved!!FLEACIDE

Flea dip

Kills fleas & Chewing Lice on contact! Guaranteed!

Active Ingredients:Rotenone: CAS# 330387-01…….. 7.0%essential oils of clove ……………. 2.0%essential oil of cinnamon………….2.0 %essential oil of fir …………………..2.0%essential oil of rosemary…………..2.0%Inert ingredients ……………………85.0%

Instructions for use: Add 1/3 cup per tub of full water . Dunk dog. Rinse. Repeat if necessary.

Made from all natural products!

Non-toxic.

1.) What could have been in the flea dip that killed the girl?

2.) How can a product that is normally harmless to humans and pets killed the girl?

3.) Is the label misleading? Why?

Autopsy Report

�The girl died within two hours of first vomiting

� Immediate cause of death was hypoxia

�Tissue sections from the kidneys, lungs, thymus, and heart show massive cell death

�Staining with cellular dyes indicates that the mitochondria within the affected tissues were damaged

•Hypoxia: is a pathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is

deprived of adequate oxygen supply.

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Normal Necrotic Cellular Staining

Kidney

Liver

Lung

�Given the autopsy report, and recalling

your knowledge from your reading about the functions of cellular organelles, what

functions of the cell did fleacide affect?

�As the medical examiner, what other

information would you want to know?

ATP Analysis

�A more detailed analysis of the cells from

the girls heart, showed that ATP levels were reduced in the mitochondria. ATP

levels in the cytoplasm of these cells, however, was normal.

�What cellular process (or processes) was impaired by the Fleacide?

13

Cellular respiration (aerobic) occurs in 3 stages

1.2.

3.

ATP

H+

Intermembranespace

O2

H2O

1−−−−2

Innermitochondrialmembrane

H+NAD+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

Mitochondrialmatrix

Electronflow

Electroncarrier

Proteincomplexof electroncarriers

NADH

FADH2 FAD

ATPsynthase

PADP +

Chemiosmosis

+ 2

OXIDATIVE PHOSPHORYLATION

Electron Transport Chain

• Using a new chromatographic technology

developed late last year, you are able to determine the levels of various subcellular

components in the heart cells.

14

• Chromatography: is the collective term

for a family of laboratory techniques for the separation of mixtures.

Gas chromatography

Thin layer chromatography

Metabolite Autopsy Finding Normal LevelsGlucose 102 mmol 100 mmolPyruvate 23 mmol 25 mmolNAD+ 6 mmol 75 mmolNADH 383 mmol 50 mmol

Subcellular Analysis

1. Given this new information, what specific cellular process

do you think was affected by the Fleacide? Why?

2. Would artificial respiration or oxygenation save the girl?

Why or why not?

ATP

H+

Intermembranespace

O2

H2O

1−−−−2

Innermitochondrialmembrane

H+NAD+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

Mitochondrialmatrix

Electronflow

Electroncarrier

Proteincomplexof electroncarriers

NADH

FADH2 FAD

ATPsynthase

PADP +

Chemiosmosis

+ 2

OXIDATIVE PHOSPHORYLATION

Electron Transport Chain

15

ATP

H+

O2

H2O

1−−−−2 H+

NAD+NADH

FADH2 FAD

PADP +

Chemiosmosis

+ 2

Electron Transport Chain

H+H+H+

H+

Rotenone Cyanide,carbon monoxide

H+ H+

Oligomycin

ATPsynthase

DNP

H+

H+

H+

Rotenone

• Rotenone is a natural plant toxin used for centuries by indigenous peoples of Southeast Asia and South America

• Rotenone is chemically unstable and breaks down rapidly in the environment, yielding water soluble non-toxic products.

• Rotenone is a highly specific metabolic poison that affects cellular aerobic respiration, blocking mitochondrial electron transport