Transcript

Biol 219 Lec 7 Fall 2016 Dr. Scott

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Cellular Respiration and Metabolism

Cellular Respiration: Harvesting Energy to form ATP

Introducing “The Players”

Glucose primary substrate for cellular respirationATP the “energy currency” moleculePyruvate end product of glycolysis; branch point between

aerobic and anaerobic metabolismLactate end product of anaerobic metabolismAcetyl CoA the 2-carbon shuttle; a key intermediate

in aerobic metabolismNAD+ oxidized coenzyme (also FAD)NADH reduced coenzyme (also FADH2):

carrier of 2 high-energy electronsO2 the final electron acceptor in aerobic metabolismCO2 end product of aerobic metabolism H2O other end product of aerobic metabolism

Glucose Oxidation: The Central Metabolic Pathway

1. Glycolysis

2. Citric Acid (Krebs) Cycle

3. Electron Transport Chain

glucose + 6 O2 → 6 CO2 + 6 H2O + energy ATPheat

Biol 219 Lec 7 Fall 2016 Dr. Scott

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Glycolysis1. Energy investment steps:

input 2 ATP

2. Cleavage step:6C → 2 x 3C

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

X 2

Summary of Glycolysis

(Aerobic -requires O2)

Glucose + 2 ADP + 2 NAD+ 2 Pyruvate + 2 ATP + 2 NADH

Anaerobic Metabolism:The Lactic Acid Pathway

• Pyruvate is converted to Lactate

• NADH is converted back to NAD+

which is needed for glycolysis

• Net yield is 2 ATP

• Pyruvate enters the matrix of the mitochondria

• Pyruvate is broken down intoa 2-carbon unit of Acetyl CoA

• Yields 1 NADHand1 CO2 is produced

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

Aerobic Metabolism: Transition from Glycolysis to the Citric Acid Cycle

Biol 219 Lec 7 Fall 2016 Dr. Scott

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The Citric Acid Cycle• 2C unit from Acetyl CoA combines with

Oxaloacetate (4C) to form Citrate (6C)

• Citrate is oxidizedin a series of stepsback to oxaloacetate

The Citric Acid Cycle

• High energy electrons are captured in the form of

reduced coenzymes:3 NADH + 1 FADH2

• 2 CO2 areproduced

• 1 ATP isformed directly

Electron Transfer in the Citric Acid Cycle

NADH and FADH2 carry the high-energy electrons to the Electron Transport Chain

High-energy electrons are transferred to NADH and FADH2 • Acetyl CoA (2C) combines with oxaloacetate (4C) to form

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.

Citric Acid Cycle Highlights

Biol 219 Lec 7 Fall 2016 Dr. Scott

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The Electron Transport Chain

Ø 3 major protein complexes (I, III, IV) located in the mitochondrial inner membraneØ NADH donates high-energy electrons to complex I (FADH2 donates further down)Ø Energy released from “downhill” flow of electrons is captured to form ATPØ O2 is the final electron acceptor at the end of the E.T.C.

Chemiosmotic Theory of ATP Synthesis

Ø Complexes I, III, IV use energy released from electron transfer to pump H+ ions“uphill” from the matrix to the intermembrane space.

Ø Energy is temporarily stored as an electrochemical gradient of H+

Ø H+ ions move “downhill” through the ATP synthase, releasing energyØ ATP synthase uses energy released to phosphorylate ADP to form ATP

Summary of Glucose Oxidation and ATP Production

(net 6 H2O)

24 e-

~ 30

Comparison of Aerobic and Anaerobic Metabolism of Glucose

Biol 219 Lec 7 Fall 2016 Dr. Scott

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Glycogen Synthesis (Glycogenesis)

Ø Glycogen is stored mostly in the liver and skeletal muscle

Ø Glycogen synthesis is stimulated by insulin

– formation of glycogen from glucose for storage

Glycogenolysis

Ø Glycogen stored in the liver helps maintain blood glucose homeostasis between meals

Ø Glycogenolysis in the liver is stimulated by glucagon

Ø Glycogen stored in muscle is metabolized during activity

– breakdown of glycogen to glucose

Summary of Glycogen Metabolism Protein Catabolism and Deamination

H+

• 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

Biol 219 Lec 7 Fall 2016 Dr. Scott

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Protein Catabolism and Deamination

H+

• Deamination removes the 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 urea to be excreted in the urine.

deamination

hydrolysis

Summary of Protein Metabolism

Fat Catabolism (Lipolysis) and Oxidation

Ø Triglycerides are broken down by hydrolysis into fatty acids + glycerol

Ø Fatty acids are broken down 2 C at a time by beta oxidation to form Acetyl CoA

Fat Catabolism (Lipolysis) and Oxidation

ØAcetyl CoA transfers 2 C units to the Citric Acid Cycle;(aerobic → CO2 + H2O)

Ø Yields > 2X more energy per gram than carbohydrates

Ø Excess fat catabolism produces ketone bodieswhich are acidic (lower pH)

Biol 219 Lec 7 Fall 2016 Dr. Scott

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Lipid SynthesisØ Acetyl CoA is a key intermediate for both

lipid catabolism and lipid synthesisØ Lipid catabolism occurs in mitochondria;

lipid synthesis occurs in smooth ER.

Summary of Fat Metabolism

beta oxidation

Gluconeogenesis

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)

Glycogen Metabolism

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deamination

hydrolysis

Protein Metabolism Fat Metabolism

beta oxidation

Gluconeogenesis

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