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DERIVATION OF
CELLULAR ENERGY
JAWAD ALI
MS 2nd Semester Biotechnology
Khawar Khan
Phd 2nd Semester Biotechnology
1
Carbohydrates Proteins Lipids
Foods
Glycolysis Proteolysis Lipolysis
2
Energy Production: Key Concepts
• Primary energy yielding compounds:
• Glucose
• Fatty Acids
• Glycerol
• Amino Acids
• ATP= Energy Currency
ATP
3
Basic Metabolic
Pathway
• Key Compounds that Enter
• Glucose
• Fatty Acids
• Glycerol
• Amino Acids
• Key End Product
• ATP
Glucose
Pyruvate
Acetyl CoA
TCA
(Krebs)
Cycle
Electron Transport Chain
4
Glucose
• Glycolysis
• Some ATP
• Glycolysis is anerobic pathway
Glucose
Pyruvate
Acetyl CoA
TCA
(Krebs)
Cycle
Electron Transport Chain
Glycolysis
ATP
5
Glucose:
Inadequate
Oxygen
• Cori cycle
• Pyruvate converted to lactate
• Lactate sent to liver
• Regenerates glucose
• Little ATP produced (when no
oxygen)
Pyruvate
Acetyl CoA
TCA
(Krebs)
Cycle
Electron Transport Chain
Glycolysis
ATP
Glucose
Anaerobic Lactate
ATP
Cori
Cycle
Fermentation (Anaerobic Respiration)
• Some prokaryotes that live in low oxygen environments rely on
anaerobic respiration (fermentation) to breakdown food.
• Fermentation and cellular respiration begin the same way, with
glycolysis but in fermentation the pyruvate made in glycolysis
does not go to Krebs cycle and ETC.
7
Lactic Acid Fermentation
8
Alcoholic Fermentation
9
Fats/Lipids
• Main form of fats
• Triglycerides
• Triglycerides:
• Glycerol
• Fatty Acids (only go down the
pathway which requires
oxygen)
Pyruvate
Acetyl CoA
TCA
(Krebs)
Cycle
Electron Transport Chain
Glycolysis
ATP
Anaerobic
ATP
Glucose
Glycerol Lactate
Cori
Cycle
Fatty
Acids
10
Amino acids
• Amino acids
• Glucogenic
• Ketogenic
• Amino Acids are stored in
muscle or different tissues
but we don’t use those
amino acids for energy. We
use amino acids from the
protein we eat in our food.
Pyruvate
Acetyl CoA
TCA
(Krebs)
Cycle
Electron Transport Chain
Glycolysis
ATP Glucose
Anaerobic Lactate
ATP
Cori
Cycle
Glucogenic A.A
Ketogenic A.A
11
12
Glycolysis
• Glycolysis is an oxygen independent pathway
• Glycolysis is the degradation of glucose
• Glycolysis can produce ATP in the absence of oxygen
• Glycolysis consists of two stages
• Energy investment phase
• Energy generation phase
13
Energy Investment Phase
14
Energy Generation Phase
15
Net Reaction
• Glucose + 2ADP + 2PO4 2Pyruvic Acid + 2ATP + 2NADH + 4H
16
Summary of Glycolysis
• Single glucose molecule produces 2 molecules of pyruvate, 2
molecules of ATP, 2 molecules of NADH and 2 molecules of water.
• 2 ATP’S are used in steps 1-3, 2 ATP molecules are generated in step 7
and 2 more ATP’s are generated in step 10.
17
Transition (Acetyl CoA Reaction)
• Occurs in the mitochondrial matrix
• Reactants = 2 pyruvates, 2 co-enzyme A (CoA), 2 NAD+
• Products = 2 Acetyl CoA, 2 NADH + H, 2CO2
18
Transition Phase
19
Structure of Mitochondria
20
• Rod shaped double
membrane bound organelle
• The membranes are made up
of phospholipids and proteins
Outer Membrane
• It is smooth and composed of equal amount of phospholipids
and proteins
• It has a large number of special proteins known as porins (allow
movement of molecules upto 5000 Daltons)
21
Inner Membrane
• More complex
• Folded into number of folds many times known as Cristae
• Folding helps to increase surface area
• Cristae and the proteins of the inner membrane helps in the
production of ATP’s (Electron Transport System)
22
Intermembrane Space
• Intermembrane space is the space between outer and inner
membrane
• Same composition as that of the cell cytoplasm
23
Matrix
• Complex mixture of proteins and enzymes which are important
for synthesis of ATP molecules, mitochondrial ribosomes,
tRNA’s and Mitochondrial DNA
24
Mitochondrial DNA
• Mitochondria have a small amount of DNA of their own
• Human mtDNA have 16500 DNA base pairs which contains 37
genes
• All these genes are essential for normal function of
mitochondria
• Mutations in the mtDNA leads to a number of diseases
25
Citric Acid Cycle (Krebs Cycle)
• Second stage of cellular respiration
• The usable energy found in food molecules is released mainly
in this cycle
• It takes place only in the presence of oxygen
• It occurs in the matrix of cell mitochondria
26
(Garrett, H 2008)27
Summary
• Citric acid cycle uses one molecule of Acetyl CoA (one glucose
molecule generates two molecules of Acety CoA) to generate one
ATP, 3 NADH, one FADH2, two Carbon dioxide and 3H+ ions
• Two additional molecules are also generated in the conversion of
pyruvic acid two Acetyl CoA prior to the start of the cycle
• The NADH and FADH2 molecules generated here are then passed
to the final step of oxidative phosphorylation (ETC) to generate more
ATP’s
28
Electron Transport Chain
• ETC is actually a series of protein complexes and electron carrier
molecules within the inner membrane of mitochondria
• Electrons are passed from one member of the transport chain to
another in a series of redox reactions
• Energy released in these reactions is captured as a proton gradient,
which is then used to make ATP in a process called chemiosmosis.
• Together, the electron transport chain and chemiosmosis make
up oxidative phosphorylation
29
Steps of ETC
1. Delivery of electrons by NADH and FADH2:
• Reduced electron carriers (NADH and FADH2) from other steps
of cellular respiration transfer their electrons to molecules near
the beginning of the transport chain
• In the process, they turn back into NAD+ and FAD, which can
be reused in other steps of cellular respiration
30
2. Electron transfer and proton pumping
• As electrons are passed down the chain, they move from a higher to
a lower energy level, releasing energy
• Some of the energy is used to pump H+ ions, moving them out of the
matrix and into the intermembrane space
• This pumping establishes an electrochemical gradient
31
3. Splitting of oxygen to form water:
• At the end of the electron transport chain, electrons are transferred to
molecular oxygen, which splits in half and takes up H+ to form water.
4. Gradient-driven synthesis of ATP:
• As H+ ions flow down their gradient and back into the matrix, they
pass through an enzyme called ATP synthase, which harnesses the
flow of protons to synthesize ATP
32
Mehta SL33
34
What does the ETC do for the cell ?
• Two functions
1. Regenerates electron carriers (NAD+ . FAD):
• NADH and FADH2 pass their electrons to the electron transport
chain, turning back into NAD+ and FAD
• This is important because the oxidized forms of these electron
carriers are used in glycolysis and the citric acid cycle and must
be available to keep these processes running
35
2. Makes a proton gradient:
• The transport chain builds a proton gradient across the inner
mitochondrial membrane, with a higher concentration of H+ in the
intermembrane space and a lower concentration in the matrix
• This gradient represents a stored form of energy, and it can be
used to make ATP
36
Summary
• Electrons are donated to ETC by NADH and FADH2
• Electrons are passed along the chain from one protein complex
to another until donated to oxygen forming water
• During the passage of electrons, protons are pumped out of the
mitochondrial matrix across the inner membrane into then
intermembrane space
37
• These protons produce an electrochemical gradient that causes
proton to flow down the gradient and back into the matrix through
ATP synthase
• This movement of protons provide energy for the production of ATP
38
39
40
Energy Per ATP Molecule
41
(ΔG= -30.5 kJ/mol)
(-7.3 Kcal/mol)
References
• Garrett, H., Reginald and Charles Grisham . Biochemistry. Boston:
Twayne Publishers, 2008.
• Raven, Peter. Biology. Boston: Twayne Publishers, 2005.
• Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New
York: W H Freeman; 2002. Chapter 17,
• The Citric Acid Cycle. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK21163/
• The Citric Acid Cycle. BioCarta. Updated March 2001.
(http://www.biocarta.com/pathfiles/krebpathway.asp)
• Mehta SL, Li PANeuroprotective role of mitochondrial uncoupling
protein 2 in cerebral stroke. J Cereb Blood Flow Metab 29:1069-
1078
42
• http://biology.tutorvista.com/animal-and-plant-
cells/mitochondria.html
43

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Derivation of cellular energy

  • 1. DERIVATION OF CELLULAR ENERGY JAWAD ALI MS 2nd Semester Biotechnology Khawar Khan Phd 2nd Semester Biotechnology 1
  • 3. Energy Production: Key Concepts • Primary energy yielding compounds: • Glucose • Fatty Acids • Glycerol • Amino Acids • ATP= Energy Currency ATP 3
  • 4. Basic Metabolic Pathway • Key Compounds that Enter • Glucose • Fatty Acids • Glycerol • Amino Acids • Key End Product • ATP Glucose Pyruvate Acetyl CoA TCA (Krebs) Cycle Electron Transport Chain 4
  • 5. Glucose • Glycolysis • Some ATP • Glycolysis is anerobic pathway Glucose Pyruvate Acetyl CoA TCA (Krebs) Cycle Electron Transport Chain Glycolysis ATP 5
  • 6. Glucose: Inadequate Oxygen • Cori cycle • Pyruvate converted to lactate • Lactate sent to liver • Regenerates glucose • Little ATP produced (when no oxygen) Pyruvate Acetyl CoA TCA (Krebs) Cycle Electron Transport Chain Glycolysis ATP Glucose Anaerobic Lactate ATP Cori Cycle
  • 7. Fermentation (Anaerobic Respiration) • Some prokaryotes that live in low oxygen environments rely on anaerobic respiration (fermentation) to breakdown food. • Fermentation and cellular respiration begin the same way, with glycolysis but in fermentation the pyruvate made in glycolysis does not go to Krebs cycle and ETC. 7
  • 10. Fats/Lipids • Main form of fats • Triglycerides • Triglycerides: • Glycerol • Fatty Acids (only go down the pathway which requires oxygen) Pyruvate Acetyl CoA TCA (Krebs) Cycle Electron Transport Chain Glycolysis ATP Anaerobic ATP Glucose Glycerol Lactate Cori Cycle Fatty Acids 10
  • 11. Amino acids • Amino acids • Glucogenic • Ketogenic • Amino Acids are stored in muscle or different tissues but we don’t use those amino acids for energy. We use amino acids from the protein we eat in our food. Pyruvate Acetyl CoA TCA (Krebs) Cycle Electron Transport Chain Glycolysis ATP Glucose Anaerobic Lactate ATP Cori Cycle Glucogenic A.A Ketogenic A.A 11
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  • 13. Glycolysis • Glycolysis is an oxygen independent pathway • Glycolysis is the degradation of glucose • Glycolysis can produce ATP in the absence of oxygen • Glycolysis consists of two stages • Energy investment phase • Energy generation phase 13
  • 16. Net Reaction • Glucose + 2ADP + 2PO4 2Pyruvic Acid + 2ATP + 2NADH + 4H 16
  • 17. Summary of Glycolysis • Single glucose molecule produces 2 molecules of pyruvate, 2 molecules of ATP, 2 molecules of NADH and 2 molecules of water. • 2 ATP’S are used in steps 1-3, 2 ATP molecules are generated in step 7 and 2 more ATP’s are generated in step 10. 17
  • 18. Transition (Acetyl CoA Reaction) • Occurs in the mitochondrial matrix • Reactants = 2 pyruvates, 2 co-enzyme A (CoA), 2 NAD+ • Products = 2 Acetyl CoA, 2 NADH + H, 2CO2 18
  • 20. Structure of Mitochondria 20 • Rod shaped double membrane bound organelle • The membranes are made up of phospholipids and proteins
  • 21. Outer Membrane • It is smooth and composed of equal amount of phospholipids and proteins • It has a large number of special proteins known as porins (allow movement of molecules upto 5000 Daltons) 21
  • 22. Inner Membrane • More complex • Folded into number of folds many times known as Cristae • Folding helps to increase surface area • Cristae and the proteins of the inner membrane helps in the production of ATP’s (Electron Transport System) 22
  • 23. Intermembrane Space • Intermembrane space is the space between outer and inner membrane • Same composition as that of the cell cytoplasm 23
  • 24. Matrix • Complex mixture of proteins and enzymes which are important for synthesis of ATP molecules, mitochondrial ribosomes, tRNA’s and Mitochondrial DNA 24
  • 25. Mitochondrial DNA • Mitochondria have a small amount of DNA of their own • Human mtDNA have 16500 DNA base pairs which contains 37 genes • All these genes are essential for normal function of mitochondria • Mutations in the mtDNA leads to a number of diseases 25
  • 26. Citric Acid Cycle (Krebs Cycle) • Second stage of cellular respiration • The usable energy found in food molecules is released mainly in this cycle • It takes place only in the presence of oxygen • It occurs in the matrix of cell mitochondria 26
  • 28. Summary • Citric acid cycle uses one molecule of Acetyl CoA (one glucose molecule generates two molecules of Acety CoA) to generate one ATP, 3 NADH, one FADH2, two Carbon dioxide and 3H+ ions • Two additional molecules are also generated in the conversion of pyruvic acid two Acetyl CoA prior to the start of the cycle • The NADH and FADH2 molecules generated here are then passed to the final step of oxidative phosphorylation (ETC) to generate more ATP’s 28
  • 29. Electron Transport Chain • ETC is actually a series of protein complexes and electron carrier molecules within the inner membrane of mitochondria • Electrons are passed from one member of the transport chain to another in a series of redox reactions • Energy released in these reactions is captured as a proton gradient, which is then used to make ATP in a process called chemiosmosis. • Together, the electron transport chain and chemiosmosis make up oxidative phosphorylation 29
  • 30. Steps of ETC 1. Delivery of electrons by NADH and FADH2: • Reduced electron carriers (NADH and FADH2) from other steps of cellular respiration transfer their electrons to molecules near the beginning of the transport chain • In the process, they turn back into NAD+ and FAD, which can be reused in other steps of cellular respiration 30
  • 31. 2. Electron transfer and proton pumping • As electrons are passed down the chain, they move from a higher to a lower energy level, releasing energy • Some of the energy is used to pump H+ ions, moving them out of the matrix and into the intermembrane space • This pumping establishes an electrochemical gradient 31
  • 32. 3. Splitting of oxygen to form water: • At the end of the electron transport chain, electrons are transferred to molecular oxygen, which splits in half and takes up H+ to form water. 4. Gradient-driven synthesis of ATP: • As H+ ions flow down their gradient and back into the matrix, they pass through an enzyme called ATP synthase, which harnesses the flow of protons to synthesize ATP 32
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  • 35. What does the ETC do for the cell ? • Two functions 1. Regenerates electron carriers (NAD+ . FAD): • NADH and FADH2 pass their electrons to the electron transport chain, turning back into NAD+ and FAD • This is important because the oxidized forms of these electron carriers are used in glycolysis and the citric acid cycle and must be available to keep these processes running 35
  • 36. 2. Makes a proton gradient: • The transport chain builds a proton gradient across the inner mitochondrial membrane, with a higher concentration of H+ in the intermembrane space and a lower concentration in the matrix • This gradient represents a stored form of energy, and it can be used to make ATP 36
  • 37. Summary • Electrons are donated to ETC by NADH and FADH2 • Electrons are passed along the chain from one protein complex to another until donated to oxygen forming water • During the passage of electrons, protons are pumped out of the mitochondrial matrix across the inner membrane into then intermembrane space 37
  • 38. • These protons produce an electrochemical gradient that causes proton to flow down the gradient and back into the matrix through ATP synthase • This movement of protons provide energy for the production of ATP 38
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  • 41. Energy Per ATP Molecule 41 (ΔG= -30.5 kJ/mol) (-7.3 Kcal/mol)
  • 42. References • Garrett, H., Reginald and Charles Grisham . Biochemistry. Boston: Twayne Publishers, 2008. • Raven, Peter. Biology. Boston: Twayne Publishers, 2005. • Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Chapter 17, • The Citric Acid Cycle. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21163/ • The Citric Acid Cycle. BioCarta. Updated March 2001. (http://www.biocarta.com/pathfiles/krebpathway.asp) • Mehta SL, Li PANeuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke. J Cereb Blood Flow Metab 29:1069- 1078 42

Editor's Notes

  1. Cytochrome C, Q= ubiquinone or Co enzyme Q
  2. NADH from Glycolysis cannot directly travel into Mitochondria. It either enter with shuttle DHAP and give G3P which will further reacts with NAD to give NADH2 in the matrix. Thus we get loss of one ATP. If the shuttle service used is OAA ( Oxalo acetate) then the NADH reacts with it and give us Malate which travels inside the mitochondria to the inside matrix where this Malate reacts with NAD to give us NADH so no loss of ATP occurs.