Lecture Notes for
Chapter 12/13/14/15/16/17 Metabolism
Essential Biochemistry
Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
Overview of Metabolism
Breaking down molecules
Building up molecules
Free energy comes from hydrolysis of ATP
© 2014 John Wiley & Sons, Inc. All rights reserved.
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
© 2014 John Wiley & Sons, Inc. All rights reserved.
Starchy foods are hydrolyzed by amylases.
Bond broken
Amylases are found in the salivary glands
© 2014 John Wiley & Sons, Inc. All rights reserved.
Proteins are hydrolyzed by proteases.
Proteases are secreted in the stomach and pancreas.
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Monomers are stored as polymers.
Fatty acids are stored
in the form of triacylglycerols (large globules) in adipocytes.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Some tissues use monosaccharides to produce glycogen.
Glycogen Structure
Electron Micrograph of a Liver Cell
Glycogen Granules
(pink)
Fat Globule (yellow)
Mitochondria (green)
© 2014 John Wiley & Sons, Inc. All rights reserved.
Glycogen breakdown occurs via phosphorolysis.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Some major metabolic pathways share a few common intermediates.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Some major metabolic pathways share a few common intermediates.
Glucose Catabolism
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Humans do not synthesize vitamins.
© 2014 John Wiley & Sons, Inc. All rights reserved.
ATP is often involved in coupled processes.
Cleavage of phosphoanhydride
bonds yields energy to drive
unfavorable reactions.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Consider the following reactions.
A highly favorable reaction
A highly unfavorable reaction © 2014 John Wiley & Sons, Inc. All rights reserved.
What’s so special about ATP?
• ATP hydrolysis drives many unfavorable reactions to completion.
• As a result, ATP acts as “energy currency”.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Glucose Metabolism
• Glycogen breakdown
• Glycolysis
• Gluconeogenesis
• Glycogen synthesis
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
First 5 Steps of Glycolysis
© 2014 John Wiley & Sons, Inc. All rights reserved.
Last 5 Steps of Glycolysis
© 2014 John Wiley & Sons, Inc. All rights reserved.
What happens to pyruvate?
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Overview of Gluconeogenesis • Many glycolytic
enzymes are used.
• Four new enzymes – Pyruvate carboxylase
– Phosphoenolpyruvate carboxykinase
– Fructose bisphosphatase
– Glucose-6-phosphatase
© 2014 John Wiley & Sons, Inc. All rights reserved.
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.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Glycogen synthesis consumes the free
energy of UTP.
• Hydrolysis of inorganic pyrophosphatase drives the reaction.
• UDP-glucose is the major intermediate.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Glycogen synthase adds glucose to extend the glycogen polymer.
© 2014 John Wiley & Sons, Inc. All rights reserved.
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!
© 2014 John Wiley & Sons, Inc. All rights reserved.
Oxidative reactions of the pentose phosphate pathway produce NADPH.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Net Reaction for the Pentose Phosphate Pathway
• Ribose derivative is produced.
• 2 NADPH molecules are formed.
• Pathway is active in rapidly dividing cells.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Summary of Glucose
Metabolism
© 2014 John Wiley & Sons, Inc. All rights reserved.
Overview of the Citric Acid Cycle
© 2014 John Wiley & Sons, Inc. All rights reserved.
The citric acid cycle is an
energy-generating cycle.
• 1 NADH = 2.5 ATP • 1 QH2 = 1.5 ATP
© 2014 John Wiley & Sons, Inc. All rights reserved.
Overview in Context
© 2014 John Wiley & Sons, Inc. All rights reserved.
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
© 2014 John Wiley & Sons, Inc. All rights reserved.
Electron transport takes place in the mitochondrion.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Amino Acid Metabolism
© 2014 John Wiley & Sons, Inc. All rights reserved.
Transamination moves amino groups between compounds.
• Transaminase = aminotransferase • A transaminase catalyzes the transfer of an amino group
to an α-keto acid. • Transamination is reversible.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Nitrogen Metabolism in Context
• Amino acids are synthesized from intermediates of glycolysis and the citric acid cycle.
• Nonessential amino acids can be synthesized.
• Essential amino acids must be obtained from food.
© 2014 John Wiley & Sons, Inc. All rights reserved.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Amino acids can be classified in terms of their catabolism.
• Glucogenic – giving rise to gluconeogenic precursors – Citric acid cycle intermediates, for example
• Ketogenic – giving rise to acetyl-CoA – Used for ketogenesis or fatty acid synthesis – Not used for gluconeogenesis
© 2014 John Wiley & Sons, Inc. All rights reserved.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Some amino acids are converted to gluconeogenic substrates via
transamination.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Some amino acids are converted to gluconeogenic substrates via
transamination.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Approximately 80% of excess nitrogen is excreted as urea.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Amino groups can be disposed of via two routes.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Lipid Metabolism In Context
• Triacylglycerols contain fatty acids attached to a glycerol backbone.
• Fatty acids are broken down
into 2C and 3C intermediates that feed into the citric acid cycle.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Triacylglycerols are the primary source of fatty acids.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Fatty acids are activated before they are degraded.
• Activated fatty acids are acylated to CoA.
• Reaction is
driven by ATP hydrolysis.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Each round of β oxidation has four reactions.
• Acyl groups are transferred via carnitine.
• Acyl-CoA is degraded into acetyl-CoA.
© 2014 John Wiley & Sons, Inc. All rights reserved.
β Oxidation is a spiral process.
Let’s look at the reactions of β oxidation
more closely.
© 2014 John Wiley & Sons, Inc. All rights reserved.
β Oxidation results in ATP production.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Top Related