patrick paralyzed case

7/31/2019 Patrick Paralyzed Case

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Why is Patrick Paralyzed?

Maureen Knabb

Department of Biology

West Chester University

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Why did Patrick lose his ability to move?

Patrick at 2: Patrick at 21:

Movie in QuickTime (mov)

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http://www.sciencecases.org/patrick_paralyzed/patrick_paralyzed.movhttp://www.sciencecases.org/patrick_paralyzed/patrick_paralyzed.mov


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Patricks History

When Patrick was 16 years old, his hand startedtwitching as he picked up a glass at dinner.

Five months later (in February 2001), he fell downthe steps at his home and was unable to climb the

steps to the bus. He went to the ER for hisprogressive weakness.

At Childrens Hospital of Philadelphia he was initiallydiagnosed with a demyelinating disease.

He was treated with anti-inflammatory drugs andantibodies for 2 years with no improvement.

What was wrong with Patrick?

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CQ1: What could be responsible

for Patricks loss of mobility?

A: His nervous system is not functioning

properly.B: His muscles are not functioning properly.

C: He cannot efficiently break down food for

energy.

D: All of the above are possible causes.

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CQ2: Which of the following processes

requires energy?

A: Creating ion gradients across membranes.

B: Muscle shortening.

C: Protein synthesis.

D: All of the above.

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Why do nerve and muscle cells

need energy? Synthetic work = building macromolecules

(e.g., Making protein)

Mechanical work = moving molecules past each other (e.g., Muscle shortening)

Concentration work = creating chemical gradients

(e.g., Storing glucose)

Electrical work = creating ion gradients

(e.g., Unequal distribution of sodium and potassium ions)

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What is energy?

Potential Energy = stored energy Chemical bonds

Concentration gradients

Electrical potential

Kinetic Energy = movement energy Heat = molecular motion

Mechanical = moving molecules past each other Electrical = moving charged particles

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Cycling between stored chemicalversus movement energy

Stored chemical energy must be released Processes that RELEASE energy

Make ATP

Catabolic/ Exergonic Movement requires energy

Processes that REQUIRE energy

Use ATP

Anabolic/ Endergonic

Energy released > Energy required

ATP plays a central role

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ATP plays a central role in energy cycling

+

Stored

chemical

energy isreleased in

catabolic

reactions to

make ATP

ATP is used

in energy

requiringreactions like

muscle

movement


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CQ3: The high energy phosphatebond in ATP is _____ and ____ energyto break the bond.

A: Easy to break, releases

B: Hard to break, requires

C: Easy to break, requires

D: Hard to break, releases

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Adenosine triphosphate (ATP)

This bond is easy to break

and requires energy!

Hydrolysis

of ATPH2O

Formation of these new bonds

releases energy

Adenosine diphosphate (ADP)

Inorganic

phosphate (Pi)

H H


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ATP plays a central role inmetabolism

ATP is NOT the highest energy molecule

intermediate energy

ATP hydrolysis releases energy

phosphate groups require low energy to break

new bonds formed release more energy thanthe energy required to break the bond

Phosphorylation by ATP increases theenergy of other molecules

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CQ4: What would happen if Patrick losthis ability to make ATP?

A: His muscles would not beable to contract.

B: His neurons would not beable to conduct electricalsignals.

C: Both A and B.

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How is ATP generated?

ATP is formed through metabolicpathways.

In metabolic pathways, the product ofone reaction is a reactant for the next.

Each reaction is catalyzed by anenzyme.

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What are enzymes?

Enzymes (usually proteins) are biological catalysts,highly specific for their substrates (reactants).

Enzymes change reactants into products throughtransition state intermediates.

Enzymes are not consumed in the reaction.

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Enzymes as Catalysts

Enzymes speed upreactions by loweringthe activation energy

of a reaction.

Enzymes DO NOTchange the overallenergy released in a

reaction.

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http://www.wiley.com/legacy/college/boyer/0470003790/animations/catalysis_energy/catalysis_energy.swfhttp://www.wiley.com/legacy/college/boyer/0470003790/animations/catalysis_energy/catalysis_energy.swf


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CQ5: Which statement about

enzymes is correct?A: Enzymes are always proteins.

B: Enzymes are consumed in a reaction.

C: Enzymes are always active.

D: All are correct.

E: None are correct.

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Enzyme Regulation

Enzymes turn on and off based on theneed of the organism

ON = Activators

Positive allosteric regulation

OFF = Inhibitors

Irreversible = must make new enzyme!

Reversible = inhibitor can come off Competitive = active site

Noncompetitive = other site = allosteric site

Feedback Inhibition

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http://www.chem.purdue.edu/courses/chm333/enzyme_inhibition.swfhttp://www.chem.purdue.edu/courses/chm333/enzyme_inhibition.swf


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CQ6: In competitive inhibition

A: the inhibitor competes with the normalsubstrate for binding to the enzyme's activesite.

B: an inhibitor permanently inactivates the

enzyme by combining with one of itsfunctional groups.

C: the inhibitor binds with the enzyme at a site

other than the active site.D: the competing molecule's shape does not

resemble the shape of the substratemolecule.

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How are metabolic pathwaysregulated?

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Feedback inhibition animation
http://programs.northlandcollege.edu/biology/Biology1111/animations/enzyme.htmlhttp://programs.northlandcollege.edu/biology/Biology1111/animations/enzyme.html


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DNA mutations can disrupt

metabolic pathways

Patrick suffered from a genetic

disease that altered the structure ofone protein. The protein was an enzyme.

The enzyme could potentially: lose its ability to catalyze a reaction. lose its ability to be regulated.

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CQ7: Consider the following metabolic pathway:A C D

B

If the enzyme responsible for converting A to C wasmutated and nonfunctional, what would happen?

A: A levels would increase; B, C, and D levels

would decrease.

B: A and B levels would increase; C and D levelswould decrease.

C: A, B and C levels would increase; D levelswould decrease.

D: A, B, C, and D levels would all decrease.

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MetabolicPathways: Glycolysis

Pathway present in almost every cell!

Takes place in the cytoplasmof the cell.

Occurs with or without oxygen.

Oxidizes glucose (6 C) to 2 pyruvate(3 C).

Overall yield = 2 ATPand 2 NADH + H+

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http://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTMLhttp://instruct1.cit.cornell.edu/Courses/biomi290/MOVIES/GLYCOLYSIS.HTML


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Important Electron Acceptors

Coenzymes NAD (Nicotinamide Adenine Dinucleotide)

NAD+ + 2H+ + 2 e- --> NADH+ + H+

FAD (Flavin Adenine Dinucleotide) FAD + 2H+ + 2 e- --> FADH2

Both molecules serve as coenzymes in

many reactions.

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Fermentation: Recycles NADH

Occurs in the cytoplasm without O2

NADH + H+ is reoxidized to NAD+

Alcoholic Fermentation = yeast cells Converts pyruvate to ethanol and CO2

Overall yield = 2 ATP

Lactate Fermentation = animal cells Converts pyruvate to lactate

Overall yield = 2 ATP

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CQ8: Consider the following metabolic pathway:Pyruvate Acetyl CoA TCA cycle

Lactate

If Patricks enzyme responsible for convertingpyruvate to acetyl CoA was inhibited, what wouldhappen?

A: Pyruvate levels would increase; acetyl CoA andlactate levels would decrease.

B: Pyruvate and lactate levels would increase;acetyl CoA levels would decrease.

C: Pyruvate, acetyl CoA, and lactate levels wouldincrease.

D: Pyruvate, acetyl CoA, and lactate levels would

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Patrick suffered from lactate acidosis

Lactate (lactic acid) and pyruvateaccumulated in his blood.

Acidosis led to: Hyperventilation

Muscle pain and weakness

Abdominal pain and nausea

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Mitochondria

Cell membrane

Outer membrane

Intermembrane space

Inner membranematrix

cytoplasm

Glucose

Na+

Glucose

2 ATP

2 NADH + H+

2 Pyruvate

No O22 Lactate (fermentation)Glycolysis

With O2

Pyruvate

Acetyl CoA

3 NADH +

H+FADH2

GTP

ATP

2 CO2

NADH +

H+

NAD+

3 NAD+

Electron transport carriers

F0F1ATPase

CO2CO2 diffuses out

of the cell

Oxaloacetate

citrateGDP + Pi

FAD

H+

H+

H+

H+

e-

e-e-

e-e-

H+

H+

ADP + Pi

ATP

O2

Oxygen diffuses into the cell

H2O

O2

Krebs cycle

Anaerobic versus aerobic metabolism

Pyruvate

dehydrogenase

enzyme


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What happened to Patrick?

He inherited a mutation

leading to a disease calledpyruvate dehydrogenasecomplex disease (PDCD).

Pyruvate dehydrogenase isan enzyme that convertspyruvate to acetyl CoA insidethe mitochondria.

The brain depends onglucose as a fuel. PDCD

degenerates gray matter inthe brain.

Pyruvate accumulates,leading to alanine and lactateaccumulation in the blood

(lactate acidosis). 29


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CQ9: Why did Patrick becomeparalyzed?

A: He inherited a genetic disease that resulted in thepartial loss of an enzyme necessary for aerobicbreakdown of glucose.

B: The enzyme that is necessary for metabolizing fatswas defective.

C: He was unable to synthesize muscle proteins dueto defective ribosomes.

D: He suffered from a severe ion imbalance due to ahigh salt diet.

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CQ10: Which food(s) can be metabolizedto generate acetyl CoA?

A: Carbohydrates

B: Fats

C: Proteins

D: Both carbohydrates

and fats

E: Carbohydrates, fatsand proteins

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Are there any treatment options forPDH deficiency?

High fat, low carbohydrate diet (ketogenic diet)

Fatty acids can form acetyl CoA which can enterthe Krebs cycle

Fatty acids

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Are there any treatment options forPDH deficiency?

Dichloroacetate (DCA) blocks the enzyme thatconverts PDH from active to inactive forms

PDH remains in the active form

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DCA blocks here


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CQ11: Dichloroacetate (DCA)administration would lead to

A: Increased production of acetyl CoA.

B: Decreased lactate accumulation.

C: Increased ATP production.

D: All of the above.

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CQ12: The loss of which of thefollowing molecules was themost criticalfor Patricksparalysis?

A: Pyruvate dehydrogenase

B: Acetyl CoA

C: Lactate

D: ATP

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What happened to Patrick?

Although his family tried to care for him at home,Patrick remained in hospitals and nursing homesuntil he died in 2006.

Patrick died due to pneumonia, sepsis, and renalfailure when he was only 21 years old.

His family mourns his loss but feels grateful thathe was able to survive for 5 years on a respirator,4 years beyond his doctors predictions.

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patrick paralyzed case

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