Biol 219 Lec 7 Fall 2016 Dr. Scott 1

Biol 219 Lec 7 Fall 2016 Dr. Scott

Cellular Respiration: Harvesting Energy to form ATP

Cellular Respiration and Metabolism

Glucose Oxidation: The Central Metabolic Pathway Introducing “The Players” ATP glucose + 6 O2 → 6 CO2 + 6 H2O + energy heat Glucose primary substrate for cellular respiration ATP the “energy currency” molecule Pyruvate end product of glycolysis; branch point between 1. Glycolysis aerobic and anaerobic metabolism Lactate end product of anaerobic metabolism Acetyl CoA the 2-carbon shuttle; a key intermediate in aerobic metabolism 2. Citric Acid NAD+ oxidized coenzyme (also FAD) (Krebs) Cycle

NADH reduced coenzyme (also FADH2): carrier of 2 high-energy electrons

O2 the final electron acceptor in aerobic metabolism 3. Electron CO2 end product of aerobic metabolism Transport H2O other end product of aerobic metabolism Chain

1 Biol 219 Lec 7 Fall 2016 Dr. Scott

Glycolysis Summary of Glycolysis 1. Energy investment steps: input 2 ATP Glucose + 2 ADP + 2 NAD+ 2 Pyruvate + 2 ATP + 2 NADH

2. Cleavage step: 6C → 2 x 3C (Aerobic - requires O2)

3. Energy capture steps: Net yield = 2 ATP an d 2 NADH (4 high-energy e-) X 2

Anaerobic Metabolism: Aerobic Metabolism: The Lactic Acid Pathway Transition from Glycolysis to the Citric Acid Cycle

• Pyruvate enters the matrix of • Pyruvate is converted to Lactate the mitochondria

+ • NADH is converted back to NAD • Pyruvate is broken down into which is needed for glycolysis a 2-carbon unit of Acetyl CoA

• Net yield is 2 ATP • Yields 1 NADH and 1 CO2 is produced

• Acetyl CoA transfers the 2C unit into the Citric Acid Cycle

2 Biol 219 Lec 7 Fall 2016 Dr. Scott

The Citric Acid Cycle The Citric Acid Cycle • 2C unit from Acetyl CoA combines with • High energy electrons are Oxaloacetate (4C) to form Citrate (6C) captured in the form of • Citrate is oxidized reduced coenzymes: in a series of steps 3 NADH + 1 FADH2 back to oxaloacetate

• 2 CO 2 are produced

• 1 ATP is formed directly

Electron Transfer in the Citric Acid Cycle Citric Acid Cycle Highlights High-energy electrons are NADH and FADH2 carry the transferred to NADH and FADH2 high-energy electrons to the • Acetyl CoA (2C) combines with oxaloacetate (4C) to form Electron Transport Chain citrate (6C)

• Citrate is oxidized in a series of steps back to oxaloacetate

• High-energy electrons are captured in reduced coenzymes: 3 NADH + 1 FADH2

• 2 CO2 are produced

• 1 ATP is formed directly

• NADH and FADH2 carry high-energy electrons to the Electron Transport Chain where most ATP is produced.

3 Biol 219 Lec 7 Fall 2016 Dr. Scott

Chemiosmotic Theory of ATP Synthesis The Electron Transport Chain

+ Ø 3 major protein complexes (I, III, IV) located in the mitochondrial inner membrane Ø Complexes I, III, IV use energy released from electron transfer to pump H ions “uphill” from the matrix to the intermembrane space. Ø NADH donates high-energy electrons to complex I (FADH2 donates further down) Ø Energy is temporarily stored as an electrochemical gradient of H+ Ø Energy released from “downhill” flow of electrons is captured to form ATP Ø H+ ions move “downhill” through the ATP synthase, releasing energy Ø O2 is the final electron acceptor at the end of the E.T.C. Ø ATP synthase uses energy released to phosphorylate ADP to form ATP

Summary of Glucose Oxidation and ATP Production Comparison of Aerobic and Anaerobic Metabolism of Glucose

24 e-

(net 6 H 2O)

~ 30

4 Biol 219 Lec 7 Fall 2016 Dr. Scott

Glycogen Synthesis (Glycogenesis) Glycogenolysis – breakdown of glycogen to glucose – formation of glycogen from glucose for storage Ø Glycogen stored in the liver Glycogen is stored mostly in Ø helps maintain blood glucose the liver and skeletal muscle homeostasis between meals

Ø Glycogen synthesis is Ø Glycogenolysis in the liver is stimulated by insulin stimulated by glucagon

Ø Glycogen stored in muscle is metabolized during activity

Summary of Glycogen Metabolism Protein Catabolism and Deamination

• Protein catabolism breaks down proteins into amino acids by hydrolysis of peptide bonds

• Occurs in the GI tract and within cells in lysosomes and proteasomes H+

5 Biol 219 Lec 7 Fall 2016 Dr. Scott

Summary of Protein Metabolism Protein Catabolism and Deamination

hydr olysis

• Deamination removes the deam ination amino group from amino acids. • Forms organic acids (keto acids) which enter glycolysis or the Krebs Cycle

• Amino group is released as NH3 then converted to H+ urea to be excreted in the urine.

Fat Catabolism (Lipolysis) and Oxidation Fat Catabolism (Lipolysis) and Oxidation

Ø Triglycerides are broken down by hydrolysis into fatty acids + ØAcetyl CoA transfers 2 C glycerol units to the Citric Acid Cycle; (aerobic → CO2 + H2O) Ø Fatty acids are broken down Ø Yields > 2X more energy per 2 C at a time by beta oxidation to form Acetyl CoA gram than carbohydrates Ø Excess fat catabolism produces ketone bodies which are acidic (lower pH)

6 Biol 219 Lec 7 Fall 2016 Dr. Scott

Summary of Fat Metabolism Lipid Synthesis Ø Acetyl CoA is a key intermediate for both lipid catabolism and lipid synthesis Ø Lipid catabolism occurs in mitochondria; lipid synthesis occurs in smooth ER.

beta oxidation

Gluconeogenesis Glycogen Metabolism

Ø Production of glucose from non-carbohydrate sources

Ø Important after glycogen stores are depleted to maintain glucose supply to the brain

Ø Gluconeogenesis is stimulated by cortisol (and glucagon)

7 Biol 219 Lec 7 Fall 2016 Dr. Scott

Protein Metabolism Fat Metabolism

hydr olysis

deam ination

beta oxidation

Gluconeogenesis