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Enzymes and Metabolism
Human Anatomy & Physiology, Sixth Edition
Elaine N. Marieb
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
1
Protein
 Macromolecules composed of combinations of 20
types of amino acids bound together with peptide
bonds
Figure 2.16
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Structural Levels of Proteins
 Primary – amino acid sequence - lys-arg-met
 Secondary – alpha helices or beta pleated sheets
(see video)
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3
Structural Levels of Proteins
Figure 2.17a-c
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Structural Levels of Proteins
 Tertiary – superimposed folding of secondary
structures
 Quaternary – polypeptide chains linked together in a
specific manner
PLAY
Chemistry of Life:
Proteins: Tertiary Structure
PLAY
Chemistry of Life:
Proteins: Quaternary Structure
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5
Structural Levels of Proteins
Figure 2.17d, e
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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
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Protein Denaturation
 Reversible
unfolding of
proteins due to
drops in pH and/
or increased
temperature
Figure 2.18a
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Protein Denaturation
 Irreversibly denatured proteins cannot refold and are
formed by extreme pH or temperature changes
Figure 2.18b
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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
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Characteristics of Enzymes
Figure 2.19
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Mechanism of Enzyme Action
 Enzyme binds with substrate
 Product is formed at a lower activation energy
 Product is released
PLAY
How Enzymes Work
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12
Mechanism of Enzyme Action
Active site
Amino acids
1
Enzyme (E)
Substrates (s)
Enzyme-substrate
complex (E–S)
H 20
2
Free enzyme (E)
3
Peptide bond
Internal rearrangements
leading to catalysis
Dipeptide product (P)
Figure 2.20
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13
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
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14
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
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Stages of Metabolism
Figure 24.3
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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)
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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
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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)
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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
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21
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
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Carbohydrate Catabolism
Figure 24.5
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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
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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
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Figure 24.6
25
Krebs Cycle
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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
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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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32
Krebs Cycle
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Figure 24.7
33
Mechanism of Oxidative Phosphorylation
Proton pumps
oxygen is the final electron
acceptor
Figure 24.8
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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
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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
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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
Figure 24.8
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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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Electronic Energy Gradient
 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
PLAY
Electron Transport
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Electronic Energy Gradient
Figure 24.9
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