Unit 2 Chapter 4 (pgs 76-80) Patrick’s case study Enzyme Notes Unit 2 Chapter 4 (pgs 76-80) Patrick’s case study

Metabolism = anabolism + catabolism

Enzymes Structure Substrate Lock and key Folded protein Active site Specific to active site Enzymes named after substrate Ex. Lactase -> lactose Lock and key

Enzyme-catalyzed reaction **Enzyme can be reused over and over how enzymes work

Activation Energy Energy needed to begin a reaction Enzymes lower activation energy Enzymes are biological catalysts

Factors the affect enzyme function Temperature (heat) pH Substrate/enzyme concentration

Why did Patrick lose his ability to move? Patrick at 2: Patrick at 21: Movie in QuickTime (mov) Movie available at http://www.sciencecases.org/patrick_paralyzed/patrick_paralyzed.mov

Patrick’s History When Patrick was 16 years old, his hand started twitching as he picked up a glass at dinner. Five months later (in February 2001), he fell down the steps at his home and was unable to climb the steps to the bus. He went to the ER for his progressive weakness. At Children’s Hospital of Philadelphia he was initially diagnosed with a demyelinating disease. He was treated with anti-inflammatory drugs and antibodies for 2 years with no improvement. What was wrong with Patrick?

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.

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

Cycling between stored chemical versus movement energy Stored chemical energy must be released Processes that RELEASE energy Make ATP Catabolic Movement requires energy Processes that REQUIRE energy Use ATP Anabolic Energy released > Energy required ATP plays a central role

ATP plays a central role in energy cycling + Stored chemical energy is released in catabolic reactions to make ATP ATP is used in energy requiring reactions like muscle movement 12 12

CQ3: The high energy phosphate bond in ATP is _____ and ____ energy to break the bond. A: Easy to break, releases B: Hard to break, requires C: Easy to break, requires D: Hard to break, releases

ATP plays a central role in metabolism 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 than the energy required to break the bond

CQ4: What would happen if Patrick lost his ability to make ATP? A: His muscles would not be able to contract. B: His neurons would not be able to conduct electrical signals. C: Both A and B.

How is ATP generated? ATP is formed through metabolic pathways. In metabolic pathways, the product of one reaction is a reactant for the next. Each reaction is catalyzed by an enzyme.

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. Note: It is a common misconception that enzymes are always active. This question leads to the next slides on enzyme regulation.

DNA mutations can disrupt metabolic pathways Patrick suffered from a genetic disease that altered the structure of one protein. The protein was an enzyme. The enzyme could potentially: lose its ability to catalyze a reaction. lose its ability to be regulated.

CQ7: Consider the following metabolic pathway: A C D B If the enzyme responsible for converting A to C was mutated 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 levels would decrease. C: A, B and C levels would increase; D levels would decrease. D: A, B, C, and D levels would all decrease.

Cellular Respiration Review pyruvic acid electrons (in NADH & FADH2) glucose Krebs Cycle glycolysis ETC ATP ATP ATP Cellular Respiration Review

CQ8: Consider the following metabolic pathway: Pyruvate Acetyl CoA TCA (kreb) cycle Lactate If Patrick’s enzyme responsible for converting pyruvate to acetyl CoA was inhibited, what would happen? This question leads specifically to some of the clinical symptoms that Patrick suffered due to his enzyme deficiency.

Patrick suffered from lactate acidosis Lactate (lactic acid) and pyruvate accumulated in his blood. Acidosis led to: Hyperventilation Muscle pain and weakness Abdominal pain and nausea The enzyme deficiency must be between the conversion of pyruvate to acetyl CoA.

What happened to Patrick? He inherited a mutation leading to a disease called pyruvate dehydrogenase complex disease (PDCD). Pyruvate dehydrogenase is an enzyme that converts pyruvate to acetyl CoA inside the mitochondria. The brain depends on glucose as a fuel. PDCD degenerates gray matter in the brain. Pyruvate accumulates, leading to alanine and lactate accumulation in the blood (lactate acidosis). The pyruvate dehydrogenase complex disease link provides more extensive information about PDCD. It is important to emphasize that the enzyme deficiency is within the mitochondria. However, alanine and lactate accumulate in the cytoplasm. The “mitochondrial membrane” box delineates the different compartments (above the box = cytoplasm, below the box = mitochondria). This image can be found at: http://www.ehponline.org/realfiles/members/1998/Suppl-4/989-994stacpoole/stacfig1.GIF

CQ9: Why did Patrick become paralyzed? A: He inherited a genetic disease that resulted in the partial loss of an enzyme necessary for aerobic breakdown of glucose. B: The enzyme that is necessary for metabolizing fats was defective. C: He was unable to synthesize muscle proteins due to defective ribosomes. D: He suffered from a severe ion imbalance due to a high salt diet.

CQ12: The loss of which of the following molecules was the most critical for Patrick’s paralysis? A: Pyruvate dehydrogenase B: Acetyl CoA C: Lactate D: ATP Even though Patrick lost PDH activity which resulted in decreased levels of acetyl CoA, ultimately Patrick’s disease was due to his inability to make ATP. This clicker question links the case back to the importance of ATP formation for cellular work.

What happened to Patrick? Although his family tried to care for him at home, Patrick remained in hospitals and nursing homes until he died in 2006. Patrick died due to pneumonia, sepsis, and renal failure when he was only 21 years old. His family mourns his loss but feels grateful that he was able to survive for 5 years on a respirator, 4 years beyond his doctor’s predictions.