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Enzymes and Metabolism

Human Anatomy & Physiology, Sixth Edition Elaine N. Marieb Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Protein  Macromolecules composed of combinations of 20 types of amino acids bound together with peptide bonds

Figure 2.16 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Structural Levels of Proteins  Primary – amino acid sequence - lys-arg-met  Secondary – alpha helices or beta pleated sheets (see video)

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Structural Levels of Proteins

Figure 2.17a-c Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Structural Levels of Proteins  Tertiary – superimposed folding of secondary structures  Quaternary – polypeptide chains linked together in a specific manner

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Chemistry of Life: Proteins: Tertiary Structure

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Chemistry of Life: Proteins: Quaternary Structure


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Structural Levels of Proteins

Figure 2.17d, e Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Fibrous and Globular Proteins

 Fibrous proteins  Extended and strandlike proteins  Examples: keratin, elastin, collagen, and certain contractile fibers  Globular proteins  Compact, spherical proteins with tertiary and quaternary structures  Examples: antibodies, hormones, and enzymes Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Protein Denaturation

 Reversible unfolding of proteins due to drops in pH and/ or increased temperature

Figure 2.18a Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Protein Denaturation  Irreversibly denatured proteins cannot refold and are formed by extreme pH or temperature changes

Figure 2.18b Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Characteristics of Enzymes  Most are globular proteins that act as biological catalysts  Holoenzymes consist of an apoenzyme (protein) and a cofactor (usually an ion ex Mg, Mb)  Enzymes are chemically specific, bind to specific substrates  Frequently named for the type of reaction they catalyze  Enzyme names usually end in -ase  Lower activation energy - catalysts, speed up reactions Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Characteristics of Enzymes


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Mechanism of Enzyme Action

 Enzyme binds with substrate  Product is formed at a lower activation energy  Product is released

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How Enzymes Work


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Mechanism of Enzyme Action Active site Amino acids

1 Enzyme (E)

Substrates (s)

Enzyme-substrate complex (E–S)

H 20

2

Free enzyme (E)

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Peptide bond Internal rearrangements leading to catalysis

Dipeptide product (P)

Figure 2.20


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Metabolism  Metabolism – all chemical reactions necessary to maintain life  Cellular respiration – food fuels are broken down within cells and some of the energy is captured to produce ATP  Anabolic reactions – synthesis of larger molecules from smaller ones  Catabolic reactions – hydrolysis of complex structures into simpler ones Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Stages of Metabolism  Energy-containing nutrients are processed in three major stages  Digestion – breakdown of food; nutrients are transported to tissues  Anabolism and formation of catabolic intermediates where nutrients are:  Built into lipids, proteins, and glycogen  Broken down by catabolic pathways to pyruvic acid and acetyl CoA  Oxidative breakdown – nutrients are catabolized to carbon dioxide, water, and ATP Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Stages of Metabolism


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Oxidation-Reduction (Redox) Reactions  Oxidation occurs via the gain of oxygen or the loss of hydrogen  Whenever one substance is oxidized, another substance is reduced  Oxidized substances lose energy  Reduced substances gain energy  Coenzymes act as hydrogen (or electron) acceptors (electron carriers)  Two important coenzymes are nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Mechanisms of ATP Synthesis: Substrate-Level Phosphorylation  High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP  ATP is synthesized via substrate-level phosphorylation in glycolysis and the Krebs cycle Figure 24.4a Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Mechanisms of ATP Synthesis: Oxidative Phosphorylation  Is carried out by the electron transport proteins in the cristae of the mitochondria  Nutrient energy is used to pump hydrogen ions into the intermembrane space  A steep diffusion gradient across the membrane results  When hydrogen ions flow back across the membrane through ATP synthase, energy is captured and attaches phosphate groups to ADP (to make ATP) Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Mechanisms of ATP Synthesis:

 Uses the chemiosmotic process whereby the movement of substances across a membrane is coupled to chemical reactions


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Mechanisms of ATP Synthesis:

Figure 24.4b Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Carbohydrate Metabolism  Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism  Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2  6H2O + 6CO2 + 36 ATP + heat  Glucose is catabolized in three pathways  Glycolysis  Krebs cycle  The electron transport chain and oxidative phosphorylation Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Carbohydrate Catabolism


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Glycolysis  A three-phase pathway in which:  Glucose is oxidized into pyruvic acid  NAD+ is reduced to NADH + H+  ATP is synthesized by substrate-level phosphorylation  Pyruvic acid:  Moves on to the Krebs cycle in an aerobic pathway  Is reduced to lactic acid in an anaerobic environment Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Glycolysis

Text

10 Step process 6C molecules are broken into 2 3C molecules 2 NADH’s generated 2 ATP spent, 4ATP generated: net 2ATP


Figure 24.6 25

Krebs Cycle


Figure 24.7 26

Glycolysis: Phase 3

 The final products are:  Two pyruvic acid molecules  Two NADH + H+ molecules (reduced NAD+)  A net gain of two ATP molecules


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Krebs Cycle: Preparatory (Intermediate) Step

 Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids  pyruvic acid has to be transferred to mitochondrion, takes energy (ATP)


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Krebs Cycle: Preparatory Step

 Pyruvic acid is converted to acetyl CoA in three main steps:  Decarboxylation  Carbon is removed from pyruvic acid  Carbon dioxide is released


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Krebs Cycle: Preparatory Step

 Oxidation  Hydrogen atoms are removed from pyruvic acid  NAD+ is reduced to NADH + H+  Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA


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Krebs Cycle (Citric Acid cycle)

OAA


Figure 24.7 31

Krebs Cycle  An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating:  Three molecules of NADH + H+  One molecule of FADH2  Two molecules of CO2  One molecule of ATP  For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle; 2 cycles per glucose molecule PLAY

Krebs Cycle


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Krebs Cycle


Figure 24.7 33

Mechanism of Oxidative Phosphorylation Proton pumps

oxygen is the final electron acceptor


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Electron Transport Chain  Food (glucose) is oxidized and the released hydrogens with electrons:  Are transported by coenzymes NADH and FADH2  Enter a chain of proteinsAt the end of chain combine with molecular oxygen to form water  Release energy  The energy released is harnessed to make a H+ gradient which allows attachment of inorganic phosphate groups (Pi) to ADP, making ATP by oxidative phosphorylation Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Mechanism of Oxidative Phosphorylation  The hydrogens delivered to the chain are split into protons (H+) and electrons  The protons are pumped across the inner mitochondrial membrane by:  NADH dehydrogenase (FMN, Fe-S)  Cytochrome b-c1  Cytochrome oxidase (a-a3)  The electrons are shuttled from one acceptor to the next Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Mechanism of Oxidative Phosphorylation  Electrons are delivered to oxygen, forming oxygen ions  Oxygen ions attract H+ to form water  H+ pumped to the intermembrane space:  Diffuses back to the matrix via ATP synthase  Releases energy to make ATP

PLAY

InterActive Physiology®: Muscular System: Muscle Metabolism


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Mechanism of Oxidative Phosphorylation


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Electronic Energy Gradient

 The transfer of energy from NADH + H+ and FADH2 to oxygen releases large amounts of energy  This energy is released in a stepwise manner through the electron transport chain


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 The electrochemical proton gradient across the inner membrane:  Creates a pH gradient  Generates a voltage gradient  These gradients cause H+ to flow back into the matrix via ATP synthase

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Electron Transport


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