Visual Anatomy & First Edition

Martini & Ober

Chapter 22 (Sections 22.1-22.4) & Lecture 8

Lecture Overview • and control of metabolic reactions • and metabolic reactions • Cellular respiration – Overview – ATP as the biological energy carrier – Oxidation/Reduction – Steps in Cellular Respiration • • The Citric (Krebs) Cycle • The • Relationship of to 2

Enzymes and Metabolic Reactions

Enzymes – Biological catalysts • control rates of metabolic reactions • lower activation energy needed to start reactions • globular with specific shapes • not consumed in chilhemical reacti ons • substrate specific • shape of active site determines which substrate(s) the can act on Figure from: Hole’s Human A&P, 12th edition, 2010

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1 Enzymes Lower Activation Energy

Enzymes lower the barriers that block chemical reactions, i.e., they lower the activation energy needed to begin energetically favorable reactions

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Control of Metabolic Reactions

Metabolic pathways • series of enzyme-controlled reactions leading to formation of a product • each new substrate is the product of the previous reaction

Enzyme names commonly Factors that alter activity of • reflect the substrate enzymes • have the suffix – ase • heat • sucrase, lactase, • radiation protease, lipase, • substrate concentration hydrolase, oxidase • required cofactors • changes in pH 6

Cofactors and Coenzymes Cofactors Coenzymes • make some enzymes • complex organic molecules active that act as cofactors (so • ions or coenzymes coenzymes ARE cofactors) • • NAD+

Vitamins are essential organic substances that human cells cannot synthesize, i.e., they must come from the diet - required in very small amounts

- examples - B vitamins: Thiamine (B1), niacin

The parts of enzymes that need a nonprotein part

(coenzymes, cofactors) to work are called apoenzymes 7

2 Overview of Cellular Metabolism

Metabolism – All the chemical reactions that occur in an

KEEP THIS OVERALL SCHEME IN MIND AS WE ETS GO INTO DETAILS!!

8 Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Overview of Breakdown

9 Figure from: Hole’s Human A&P, 12th edition, 2010

Overview of Catabolism

Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011 11

3 A Closer Look at Mitochondria

Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

(Impermeable to charged or polar molecules)

Strategically placed in where ATP demand is high

Concentration of enzymes in the matrix is so high that there is virtually no hydrating . Enzyme-linked reactions and pathways are so crowded that normal rules of diffusion do not apply! 12

Carbohydrate Metabolism • Most cells generate ATP and other energy- yielding compounds via the catabolism of (and ) General Reaction sequence in

C6H12O6 + 6 O2  6 CO2 + 6 H2O + ENERGY

If the above reaction happened all at once, all the chemical energy contained in the carbohydrate would be DISSIPATED AS HEAT. How does the body harness the energy from ?

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Harnessing Energy - Stepwise Breakdown of Carbohydrates

14 Figure from: Alberts et al., Essential Cell , Garland Press, 1998

4 Energy for Metabolic Reactions

Energy • ability to do work or change something (potential, kinetic) • heat, light, sound, electricity, mechanical energy, chemical energy • changed from one form to another, but NEVER destroyed (law of conservation of energy) • invol ved i n all met ab oli c reacti ons

Release of chemical energy • most metabolic processes depend on chemical energy • oxidation of glucose generates chemical energy • cellular respiration releases chemical energy slowly from molecules and makes it available for cellular use

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Oxidation and Reduction Revisited

Oxidation

• gain of O2 • loss of e- • loss of H (since a H carries an electron with it) • increase in oxidation number, e.g., Fe2+ -> Fe3+

Reduction

• loss of O2 • gain of e- • gain of H • decrease in oxidation number, e.g., Fe3+ -> Fe2+

Oxidation Is Loss of electrons; Reduction Is Gain of electrons “OIL RIG” 16

Energy of Organic Molecules • Carbohydrates like glucose store a great deal of chemical energy (as H·)

•As carbohydrates (C6H12O6) are oxidized to CO2 they liberate their energy and lose electrons and H (H·) • But there must be molecules to accept these electrons, i.e., some molecules must be reduced.

• In cellular respiration, O2 becomes the final electron (H·) acceptor and is reduced to H2O

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5 Harnessing Energy from Carbohydrates

General Reaction sequence in carbohydrate catabolism OXIDATION

C6H12O6 + 6 O2  6 CO2 + 6 H2O + ENERGY

REDUCTION Electrons (H·) “fall” in energy from organic molecules to during cellular respiration. That is, e- LOSE potential energy during this process and this energy is captured to make ATP However, electrons CANNOT be transferred directly from glucose to the electron transport chain. There are intermediates – activated carrier molecules 18

Activated Carrier Molecules

Some activated carriers: ATP, NADH, FADH2, GTP, NADPH

19 Figure from: Alberts et al., Essential , Garland Press, 1998

ATP – An Activated Carrier Molecule

Figure from: Hole’s Human A&P, 12th edition, 2010 • each ATP molecule has three parts:

• an molecule These two components • a molecule together are called a ? • three molecules in a chain

• ATP carries its energy in the form or P (phos phate )

• ATP is a readily interchangeable form High-energy of energy for cellular reactions bonds (“common currency”)

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6 NAD(H) – An Activated Carrier Molecule

NAD+ NAD (and NADP) are specialized to carry high-energy e- and H atoms

NADH + H+ A “packet” of energy = H·

NAD+ NADH

These packets of energy will be passed to oxygen in the electron transport chain, and their energy used to drive the synthesis of ATP

- Important carriers of e in catabolism: NADH, FADH2 21 Figure from: Alberts et al., Essential Cell Biology, Garland Press, 1998

Overview of Cellular Respiration

Anaerobic Cellular respiration (aerobic)

22 Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Overview of Glucose Breakdown

Figure from: Hole’s Human A&P, 12th edition, 2010

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7 Overview of Glucose Breakdown Occurs in three major of reaction series… 1. Glycolysis (glucose to pyruvate; in ) 2. cycle (finishes oxidation begun in glycolysis; in the matrix of mitochondria) 3. Electron transport chain (uses e- transfer to make ATP; on inner membranes of mitochondria) Produces • • water • ATP (chemical energy) • heat (energy has changed form from chemical) Includes

• anaerobic reactions (without O2) - produce little ATP • aerobic reactions (requires O2) - produce most ATP 24

Glycolysis • series of ten reactions

• breaks down glucose (6C) into 2 molecules of (pyruvate) (3C)

• occurs in

• anaerobic phase of cellular respiration (that is, it can

continue to work with OR without O2)

• yields 2 ATP and 2 NADH molecules per glucose

ADP + Pi ATP Glucose (6C) 2 Pyruvate (3C)

NAD+ NADH 25

Overview of Glycolysis glucose (6C) → 2 pyruvate (3C) Figure from: Hole’s Human A&P, 12th edition, 2010

Products of glycolysis - ATP - NADH - Pyruvate

NOTE what happens with and without O2 being available…

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8 Metabolism of Pyruvate Without O2

• process of forming lactate from glucose is anerobic glycolysis

• important for regenerating NAD+ so glycolysis can continue to generate ATP for the cell

O2 Pyruvic acid (pyruvate) (lactate)

NADH + H+ NAD+

NAD+ NADH + H+ Glucose (6C) 2 Pyruvate (3C)

ADP + Pi ATP

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Overview of Aerobic Reactions

Figure from: Hole’s Human A&P, 12th edition, 2010 If oxygen is available – • pyruvic acid is used to produce acetyl CoA • citric acid (Krebs) cycle begins • electron transport chain functions • carbon dioxide and water are formed • maximum of 36 molecules of ATP produced per glucose molecule

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Citric Acid Cycle

Figure from: Hole’s Human A&P, 12th edition, 2010 In mitochondria…

What happens…

- Acetyl CoA enters cycle - Citric Acid is converted to various intermediates - SlSeveral ittdtimportant products are produced in these interconversions of citric acid…

• ATP is produced •NAD+ is reduced to NADH and FAD is

reduced to FADH2 • CO2 produced 29

9 Source of e- for the Electron Transport Chain

Figure from: Hole’s Human A&P, 12th edition, 2010

Notice the flow of electrons to the Electron Transport Chain

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Electron Transport Chain

• NADH and FADH2 carry electrons to the ETC • ETC series of electron carriers located in cristae of mitochondria • energy from electrons transferred to ATP synthase • ATP synthase catalyzes the oxidative of ADP to ATP • water is formed

*

Figure from: Hole’s Human A&P, 12th edition, 2010 31

Oxidative Phosphorylation

Chemiosmosis, Chemiosmotic coupling, or Chemiosmotic phosphorylation

32 Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

10 Summary of Cellular Respiration

Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

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Is This All the Metabolism There Is?

Definitely NOT!

NtiNotice h ow many lines connect pyruvate and Acetyl CoA to the rest of metabolism

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Intermediates of Metabolism

Acetyl CoA (2C) and Pyruvate (3C) are important: Allow interconversion of different types of molecules so cell’s needs can be met

Figure from: Martini, Visual Anatomy & Physiology, Pearson, 2011

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11 Figure from: Hole’s Human A&P, 12th edition, 2010 Summary of Catabolism of Proteins, Carbohydrates, and Fats Acetyl CoA is a common intermediate in the breakdown of most . Acetyl CoA can be generated by carbohydrates, fats, or amino Acetyl CoA can be converted into fatty

acids 36

Pyruvate is a Key Junction in Metabolism

Pyruvate is used to synthesize   amino acids and Lipo-  genesis Acetyl CoA  Pyruvate can also be used to synthesize * glucose via .

37 Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Carbohydrate Storage Excess glucose can be • stored as glycogen by glycogenesis (liver and muscle cells) • stored as by • converted to amino acids

38 Figure from: Hole’s Human A&P, 12th edition, 2010

12 Terms to Know…

-olysis  breakdown of -neo  new -genesis  creation of • Glycolysis – metabolism of glucose to pyruvate • Gluconeogenesis – metabolism of pyruvate to glucose (making CHO from non-CHO source) • Glycogenesis – metabolism of glucose to glycogen • Glycogenolysis – metabolism of glycogen to glucose • Lipolysis – breakdown of triglyceride into and fatty acids • Lipogenesis – creation of new triglyceride (fat)

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Review • Enzymes are biological catalysts – Highly specific for their substrate – Lower activation energy needed to start a reaction – Are not consumed during reaction – Mayyq require cofactors/coenz ymes – Effectiveness is greatly affected by temperature, pH, and the presence of required cofactors • The goal of metabolism is to provide the cell with energy (catabolism) and materials for the manufacture of cellular components (anabolism) 40

Review • Cells derive energy mainly from carbon compounds like carbohydrates and fats – These substances contain a great deal of energy stored in their chemical bonds – This energy must be liberated in stepwise fashion – Activated carriers serve as intermediates to capture the energy liberated at each step • Energy is the ability to do work – May be potential or kinetic – Changes form – Is never destroyed (only converted to another form) 41

13 Review • Anabolism is intimately tied to catabolism – Energy derived from catabolism is used to drive anabolic reactions – Some molecules are important junctions between catabolism and anabolism – Acetyl CoA • Generated from pyruvate , fatty acids , and amino acids • Can be used to synthesize fatty acids and other molecules • CANNOT be used to generate pyruvate – Pyruvate • Can be synthesized from glucose and amino acids • can be used to synthesize amino acids, glucose and acetyl CoA – NOTE, however, that in humans fatty acids cannot be converted to glucose

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