Chem 150 Unit 12 Metabolism

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Chem 150Unit 12 - Metabolism

• Metabolism is the sum total of all the reactions
  that take place in a living cell. These reactions
  are used to extract energy and materials form the
  environment (catabolism), and to use this energy
  and these materials to produce new molecules
  (anabolism ) that will sustain the cell and allow
  it to to propagate itself. There are literally
  thousands of reactions involved in metabolism,
  but we will focus our attention on a core set of
  reactions that will allow us to understand some
  of core principals that define metabolism.

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Introduction

• In this unit we will look at some themes which
  define metabolism.
• There are literally thousands of chemical
  reactions that take place in a living cell
• If you wrote the chemical equations for all of
  these reactions down on a single piece of paper,
  it would look something like this

View the Metabolic Chart
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Introduction

• Some of the themes include
• The reactions are arranged into pathways, where
  the product for one reaction is the reactant
  (substrate) for the next reaction.
• The arrangement of reactions looks very much like
  a wiring diagram, but instead of tracing the flow
  of electrons, the metabolic pathways trace the
  flow of atoms and molecules.
• Every chemical reaction in metabolism is
  catalyzed by an enzyme.
• The enzymes are used like valves to control the
  flow of material through the pathways.
• Nonspontaneous reactions are driven by coupling
  them to spontaneous reactions.
• An outside source of energy is needed drive
  metabolism

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Pathways, Energy, and Coupled Reactions

• Metabolic reactions are arranged in pathways
• The product of one reaction is the substrate for
  the next reaction in the pathway.
• There are different topologies for metabolic
  pathways.

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Pathways, Energy, and Coupled Reactions

• The molecules that are placed along the pathway
  are the intermediates in the reactions
• Other reactants and products are usually
  represented by side arrows
• This reaction equation could also be written as

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Pathways, Energy, and Coupled Reactions

• When two reactions are connected through a common
  intermediate, they are said to be coupled.
• The coupling of reactions allows spontaneous
  reactions to drive nonspontaneous reactions.

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Pathways, Energy, and Coupled Reactions

• The phosphorylation of ADP can be coupled to the
  dephosphorylation of 1,3-Bisphosphoglycerate

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Pathways, Energy, and Coupled Reactions

• The phosphorylation of ADP can be coupled to the
  dephosphorylation of 1,3-Bisphosphoglycerate

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Overview of Metabolism

• Metabolism
• The sum of all reactions that take place in a
  living organism.
• Metabolism Catabolism Anabolism
• Catabolism - larger molecules are broken down
  into smaller ones in a process that usually
  releases energy
• Anabolism - larger molecules are made from small
  ones in a process the usually requires energy

View the Metabolic Chart
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Overview of Metabolism

• One of the common links between catabolism and
  anabolism is ATP.
• ATP is used to shuttle chemical energy from
  catabolism to anabolism.

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Overview of Metabolism

• One of the common links between catabolism and
  anabolism is ATP.
• ATP is used to shuttle chemical energy from
  catabolism to anabolism.

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Overview of Metabolism

• This is done by coupling the spontaneous
  reactions in catabolism to the phosphorylation of
  ADP to produce ATP
• And then coupling the unfavorable reactions in
  anabolism to the hydrolysis of ATP

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Overview of Metabolism

• The biological oxidation/reduction agents NAD
  and FAD are also used to shuttle energy from the
  favorable oxidations that take place in
  catabolism, to the unfavorable reductions that
  take place in anabolism

catabolism
anabolism
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Overview of Metabolism

• Catabolism
• Occurs in stages.
• Occupies the center of the metabolic chart.

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Overview of Metabolism

• The reactions from Acetyl-Co and below require
  molecular oxygen (O2).
• These reactions take place in a specialized
  organelle called the mitochondria.

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Digestion

• Digestion is the first stage of metaboism in
  which large molecule are broken done in small
  molecules that can be absorbed into the blood in
  the small intestine.
• Most of these reactions are hydrolysis reactions
• Proteins are hydrolyzed in to amino acids
• Polysaccharides are hydrolyzed into
  monosaccharides
• Triglycerides are hydrolyzed into fatty acids and
  glycerol.

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Glycolysis

• Glycolysis is a series of 10 coupled reactions
• The pathway starts with glucose that comes into a
  cell from the blood and is immediately
  phosphorylated to glucose-6-phosphate.
• The phosphorylation traps the glucose in the
  cell.
• The pathway then goes on to split (lyse) the the
  6-carbon glucose molecule into two 3-carbon
  molecules and to oxidize these to a-keto acids
  (Pyruvic acid).
• The energy released in the pathway is used to
  produce two types of energy rich molecules
• Two molecules of ADP are phosphorylated to ATP.
• Two molecules of NAD are reduced to NADH/H.

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Glycolysis

• Step 1 Glucose is brought into the cell and
  phosphorylated.
• The phosphorylation is coupled to the hydrolysis
  of ATP.

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Glycolysis

• Step 2 Glucose-6-phosphate (an aldohexose) is
  isomerized to fructose-6-phosphate (a
  ketohexose).
• This reaction occurs near equilibrium, which
  allows it to go in either direction.

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Glycolysis

• Step 3 Fructose-6-phosphate is phosphorylated to
  fructose-1,6-bisphosphate.
• This reaction is coupled to the hydrolysis of
  ATP.
• This sets things up for the cleavage, which
  occurs in the next step.
• So far 2 ATPs have been used instead of produced.

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Glycolysis

• Step 4 Fructose-1,6-bisphosphate splits into two
  three carbon monosaccharides
• Glyceraldehyde-3-phophate.
• Dihydroxyacetone phosphate

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Glycolysis

• Step 5 Dihydroxyacetone phosphate is isomerized
  to glyceraldehyde-3-phosphate.
• The last five reactions in glycolysis start with
  glyceraldehyde-phosphate.
• The remaing reactions will couple the oxidation
  of glyceraldhyde-3-phosphate to the production of
  ATP and NADH/H.

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Glycolysis

• Step 6 Glyceraldehyde-3-phosphate is oxidized to
  1,3-Bisphosphoglycerate.
• The oxidation of the aldehyde to an acid is
  coupled to the reduction of NAD to NADH/H and
  the phosphorylation of the acid to a mixed
  phosphate anhydride.
• The hydrolysis of a phosphate anhydride has a
  large negative ?G.

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Glycolysis

• Step 7 The hydrolysis of the phosphate from
  1,3-bisphosphoglycerate is coupled to the
  phosphorylation of ADP to generate ATP
• Since two 1,3-bisphosphoglycerates are produced
  per glucose molecule, the two ATPs that were
  invested in the first part of glycolysis have now
  been recovered.

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Glycolysis

• The remaining three steps will convert the
  phosphate ester in 3-phosphoglycerate into a
  phosphate whose hydrolysis can be coupled to the
  phosphorylation of ADP to produce ATP.
• Phosphate esters do not have a large enough
  negative ?G to be coupled to the phosphorylation
  of ADP.

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Glycolysis

• Step 8 3-Phosphoglycerate is isomerized to
  2-phosphoglycerate.
• The phosphate ester is moved form carbon 3 to
  carbon 2.
• Like most isomerization reactions, this reaction
  can go in either direction.

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Glycolysis

• Step 9 2-Phosphoglycerate is dehydrated to form
  phosphoenolpyruvate.
• The dehydration of the alcohol produces a double
  bond between carbons 2 and 3.
• This produces a phosphate with a large negative
  free energy for hydrolysis, which can now be
  coupled to the phosphorylation of ADP.

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Glycolysis

• Step 10 The hydrolysis of the phosphate from
  phosphoenolpyruvate is coupled to the
  phosphorylation of ADP.
• The hydroxyl group that is produced next to the
  carbon-carbon double-bond spontaneously
  isomerizes to a ketone.

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Glycolysis

• The net reaction for coupling all ten steps in
  glycolysis
• The energy released in the pathway is used to
  produce two types of energy rich molecules
• Two molecules of ADP are phosphorylated to ATP.
• Two molecules of NAD are reduced to NADH/H.

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Glycolysis

• Fates of pyruvate when molecular oxygen cannot be
  used to reoxidize the NADH/H back to NAD.
• The fermentation pathways provide away of
  reoxidizing NADH/H back to NAD, so that it can
  be used to keep glycolysis going.

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Gluconeogenesis

• Gluconeogenesis is the synthesis of glucose from
  pyruvate
• It uses 7 out of the 10 reactions from
  glycolysis.
• The remaining three have too large a negative
  free energy to be reversed.
• These include steps
• 1, 3 and 10
• Alternative reactions are used to get around
  these falls.

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Glycogen Metabolism

• When glucose is not needed to meet energy needs,
  it can be stored as the polysaccharide glycogen
  and used for future energy needs.
• The liver and the muscles are where glycogen is
  synthesized and stored.
• The muscles store it for future muscular
  activity.
• The liver stores it to help regulate blood
  glucose levels.

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Glycogen Metabolism
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Citric Acid Cycle

• If an organism can utilize molecular oxygen to
  accept electrons from the reduced nucleotides
  NADH/H and FADH2, then the pyruvate from
  glycolysis can be completely oxidized to CO2 and
  H2O.
• These reactions occur within a cellular organelle
  called the mitochondria.
• The first step in the complete oxidation is the
  decarboxylation of pyruvate to produce
  Acetyl-S-CoA.

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Citric Acid Cycle

• The Acetyl-CoA is fed into the citric acid cycle,
  where its two carbons are oxidized to CO2.
• In the process
• 3 more NAD are reduced to NADH/H
• 1 FAD is reduced to FADH2
• 1 GDP is phosphorylated to GTP

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Citric Acid Cycle
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Citric Acid Cycle

• The net reaction for coupling all 8 steps in
  glycolysis

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Electron Transport Chain andOxidative
Phosphorylatioin

• The reoxidation of the NADH/H to NAD and FADH2
  to FAD using molecular oxygen (O2) as the
  oxidizing agent, is carried out by the electron
  transport chain.
• The electron transport chain is located within
  the inner membrane of mitochondria.

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Electron Transport Chain andOxidative
Phosphorylatioin
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Electron Transport Chain andOxidative
Phosphorylatioin

• The reoxidation of the NADH/H to NAD and FADH2
  to FAD using molecular oxygen (O2) as the
  oxidizing agent, is carried out by the electron
  transport chain.
• The energy released in the reoxidation is coupled
  to the synthesis of ATP from ADP and Pi by the
  enzyme ATP synthase.
• The coupling involves the creation of a hydrogen
  ion concentration gradient across the inner
  mitochondrial membrane.
• The energy for synthesizing the ATP comes from
  allowing the the hydrogen ions to flow back
  across the membrane.

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The End