essential biochemistry · 2016-03-17 · glycogenolysis • glycogen breakdown occurs via different...
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Lecture Notes for
Chapter 12/13/14/15 Metabolism I
Essential Biochemistry
Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
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Overview of Metabolism
Breaking down molecules
Building up molecules
Free energy comes from hydrolysis of ATP
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Cells take up the products of digestion.
• Human diet consists of four types of biomolecules – Proteins – Nucleic acids – Polysaccharides – Fats (particularly triacylglycerols)
• Digestion reduces biomolecules to monomers – Amino acids – Nucleotides – Monosaccharides – Fatty acid
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Starchy foods are hydrolyzed by amylases.
Bond broken
Amylases are found in the salivary glands
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Proteins are hydrolyzed by proteases.
Proteases are secreted in the stomach and pancreas.
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Fatty acids are hydrolyzed by lipases.
Remember: Fatty acids are technically not
polymers.
Lipases are made in the
pancreas and secreted in the
small intestines.
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Monomers are stored as polymers.
Fatty acids are stored
in the form of triacylglycerols (large globules) in adipocytes.
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Some tissues use monosaccharides to produce glycogen.
Glycogen Structure
Electron Micrograph of a Liver Cell
Glycogen Granules
(pink)
Fat Globule (yellow)
Mitochondria (green)
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Glycogen breakdown occurs via phosphorolysis.
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Some major metabolic pathways share a few common intermediates.
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Some major metabolic pathways share a few common intermediates.
Glucose Catabolism
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Many metabolic pathways include oxidation-reduction reactions.
• Catabolism of amino acids, monosaccharides, and fatty acids involves oxidizing carbon.
• Anabolism of amino acids, monosaccharides, and fatty acids involves reducing carbon.
Carbon in methane is most highly reduced.
Carbon in CO2 is most highly
oxidized.
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Carbons in fatty acids and carbohydrates are oxidized to CO2.
Fatty acids have many methylene
carbons that undergo
oxidation.
Carbohydrates have (CH2O) carbons that
undergo oxidation.
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Overview of Metabolism
• Monomers are formed.
• Intermediates with two or three carbons are formed.
• Carbons are fully oxidized to CO2.
• Electron carriers gain electrons.
• Electron carriers are recycled via electron loss.
• ATP and H2O are produced.
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Humans do not synthesize vitamins.
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ATP is often involved in coupled processes.
Cleavage of phosphoanhydride
bonds yields energy to drive
unfavorable reactions.
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Consider the following reactions.
A highly favorable reaction
A highly unfavorable reaction © 2014 John Wiley & Sons, Inc. All rights reserved.
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What’s so special about ATP?
• ATP hydrolysis drives many unfavorable reactions to completion.
• As a result, ATP acts as “energy currency”.
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Glucose Metabolism
• Glycogen breakdown
• Glycolysis
• Gluconeogenesis
• Glycogen synthesis © 2014 John Wiley & Sons, Inc. All rights reserved.
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Glycolysis Overview
• Glycolysis occurs in 10 steps. – Steps 1-5 = energy investment – Steps 6-10 = energy payoff
• Glucose (a six-carbon molecule) is broken
down into two 3-carbon molecules.
• Electron carriers are reduced.
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First 5 Steps of Glycolysis
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Last 5 Steps of Glycolysis
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What happens to pyruvate?
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Pyruvate is a precursor of oxaloacetate.
• Oxaloacetate is a metabolite used in: – The citric acid cycle – Gluconeogenesis
• Oxaloacetate is also an intermediate in amino acid synthesis.
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Overview of Gluconeogenesis • Many glycolytic
enzymes are used.
• Four new enzymes – Pyruvate carboxylase
– Phosphoenolpyruvate carboxykinase
– Fructose bisphosphatase
– Glucose-6-phosphatase
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If glycolysis and gluconeogenesis occurred simultaneously, there
would be a net consumption of ATP!
• Goal of producing ATP would be futile!
• Instead, glycolysis and gluconeogenesis are regulated based on the cell’s needs.
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Glycogen synthesis consumes the free
energy of UTP.
• Hydrolysis of inorganic pyrophosphatase drives the reaction.
• UDP-glucose is the major intermediate.
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Glycogen synthase adds glucose to extend the glycogen polymer.
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Glycogenolysis
• Glycogen breakdown occurs via different reactions. – Linear chains are broken down via phosphorolysis. – Branched chains of glycogen are broken down via
hydrolysis.
• Glucose-6-phosphate can enter glycolysis at Step 2. – One less ATP is consumed compared to glucose from the
bloodstream. – Net gain of ATP is higher!
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Oxidative reactions of the pentose phosphate pathway produce NADPH.
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Net Reaction for the Pentose Phosphate Pathway
• Ribose derivative is produced.
• 2 NADPH molecules are formed.
• Pathway is active in rapidly dividing cells.
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Summary of Glucose
Metabolism
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Overview of the Citric Acid Cycle
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The citric acid cycle is an
energy-generating cycle.
• 1 NADH = 2.5 ATP • 1 QH2 = 1.5 ATP
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Overview in Context
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Recap on Oxidation-Reduction
• One reactant is in its oxidized state while the other is in its reduced state.
• Loss of electrons = oxidation • Gain of electrons = reduction
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Electron transport takes place in the mitochondrion.
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