Linked Data in Production: Moving Beyond Ontologies
Carbohydrate Metabolism
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2. 6CO 2 + 6H 2 O 2840 kJ Energy As Heat Combustion of glucose in a bomb calorimeter Glucose
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13. 4 stages of aerobic respiration Stage 1: Glycolysis Stage 2: Formation of Acetyl coenzyme A Stage 3: The Citric Acid Cycle Stage 4: Electron transport chain
14. A Road Map for Cellular Respiration Cytosol Mitochondrion High-energy electrons carried by NADH High-energy electrons carried mainly by NADH Glycolysis Glucose 2 Pyruvic acid Krebs Cycle Electron Transport
20. GLYCOLYSIS Glucose ATP hexokinase ADP Glucose 6-phosphate p hosphogluco- i somerase Fructose 6-phosphate ATP phosphofructokinase ADP Fructose 1,6- bis phosphate aldolase triose phosphate isomerase Dihydroxyacetone Glyceraldehyde phosphate 3-phosphate
21. Glyceraldehyde 3-phosphate glyceraldehyde NAD + + P i 3-phosphate NADH + H + dehydrogenase 1,3- Bis phosphoglycerate ADP phosphoglycerate kinase ATP 3-Phosphoglycerate phosphoglyceromutase 2-Phosphoglycerate enolase H 2 O Phospho enol pyruvate ADP pyruvate kinase ATP Pyruvate
23. Glycolysis: stage 1 The three steps of stage 1 begin with the phosphorylation of glucose by hexokinase Energy used, none extracted
24. ATP ADP glucose glucose 6-phosphate ∆ G o = -16.7 kJ/mole Step 1: Adding a phosphate Enzyme: hexokinase
25. Phosphoryl transfer reaction. Kinases transfer phosphate from ATP to an acceptor. Hexokinase has a more general specificity in that it can transfer phosphate to other sugars such as mannose. Δ G°’= -4.0 kcal mol-1
26. Glucose phosphorylation: step 1 Glucose is a relatively stable molecule and is not easily broken down. The phosphoylated sugar is less stable. ATP serves as both source of phosphate and energy needed to add phosphate group to the molecule.
27. Induced fit in hexokinase Conformation Changes on binding glucose, the two lobes of the enzyme come together and Surround the substrate
28. Step 2: Isomerization glucose 6-phosphate fructose 6-phophate aldose to ketose isomerization reversible, G°´= 1.7 kJ/mole 6 carbon ring 5 carbon ring Enzyme: phosphoglucoisomerase
29. The conversion of an aldose to a ketose . Phosphoglucose Isomerase Δ G°’= .40 kcal mol-1
30. Formation of fructose-6-phosphate: step 2 by phosphoglucose isomerase The enzyme opens the ring, catalyzes the isomerization, and promotes the closure of the five member ring.
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32. Phosphofructokinase-1 PFK Δ G°’= -3.4 kcal mol -1 The 2 nd investment of an ATP in glycolysis. Bis means two phosphate groups on two different carbon atoms. Di means two phosphate groups linked together on the same carbon atom. PFK is an important allosteric enzyme regulating the rate of glucose catabolism and plays a role in integrating metabolism.
33. Formation of fructose 1,6-bisphosphate: step 3 by phosphofructokinase (PFK): an allosteric enzyme that regulates the pace of glycolysis.
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35. Glycolysis: stage 2 Two 3-carbon fragments are produced from one 6-carbon sugar No energy used or extracted
36. Step 4: Cleavage to two triose phosphates Reverse aldol condensation ; converts a 6 carbon atom sugar to 2 molecules, each containing 3 carbon atoms. Enzyme: aldolase
44. Step 6: Formation of 1,3-Bisphosphoglycerate Done in two steps glyceraldehyde 3-phosphate 1,3 bisphosphoglycerate Enzyme: glyceraldehyde-3-phosphate dehydrogenase addition of phosphate, oxidation, production of NADH, formation of high energy compound
45. The fate of glyceraldehyde 3-phosphate Stage 3: The energy yielding phase. Glyceraldehyde 3-phosphate DH Δ G°’ = 1.5 kcal mol -1 1,3-BPG has a high phosphoryl-transfer potential. It is a mixed anhydride. An aldehyde is oxidized to carboxylic acid and inorganic phosphate is transferred to form acyl-phosphate. NAD + is reduced to NADH. Notice, under anaerobic conditions NAD + must be re-supplied.
47. Step 7: Transfer of phosphate to make ATP Formation of ATP from 1,3-Bisphosphoglycerate: Enzyme: phosphoglycerate kinase first substrate level phosphorylation, yielding ATP 2 1,3 bis PG yield 2 ATPs, thus ATP yield = ATP input high free energy yield, G°´= -18.8kJ/mole drives several of the previous steps
48. 7: Phosphoglycerate Kinase Substrate-level phosphorylation Δ G°’ = -4.5 kcal mol -1 ATP is produced from P i and ADP at the expense of carbon oxidation from the glyceraldehyde 3-phosphate DH reaction. Remember: 2 molecules of ATP are produced per glucose. At this point 2ATPs were invested and 2ATPs are produced.
53. Step 9: Removal of Water leadsto formation of double bond little energy change in this reaction, ΔG = + 1.7 kJ/mole because the energy is locked into enolphosphate. Phosphate group attached by unstable bond, therefore high energy Enzyme: enolase
54. Generation of second very high energy compound by a dehydration reaction Enolase Δ G°’ = .4 kcal mol -1 Dehydration reaction PEP the energy is locked into the high energy unfavorable enol configuration by phosphoric acid ester
55. An enol phosphate is formed: step 9 Dehydration elevates the transfer potential of the phosphoryl group, which traps the molecule in an unstable enol form Enol: molecule with hydroxyl group next to double bond
56. Step 10: Formation of Pyruvate & ATP Enzyme: pyruvate kinase phosphoenolpyruvate pyruvate second substrate level phosphorylation yielding ATP highly exergonic reaction, irreversible , ΔG = -31.4 kJ/mole.
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58. Maintaining Redox Balance NAD + must be regenerated for glycolysis to proceed Glycolysis is similar in all cells, the fate of pyruvate is variable
61. The Conversion of Glucose to Pyruvate Glucose + 2 P i + 2 ADP + 2 NAD + -> 2 pyruvate + 2 ATP + 2 NADH +2 H + The Energy released from the anaerobic conversion of glucose to pyruvate is -47kcal mol -1 . Under aerobic conditions much more chemical bond energy can be extracted from pyruvate. The question still remains: How is NAD + supplied under anaerobic conditions? Or how is redox balance maintained?
62. Under anaerobic conditions pyruvate is converted to lactate. Exercising muscle is an example. The NAD + that is consumed in the glyceraldehyde 3-phosphate reaction is produced in the lactate DH reaction. The redox balance is maintained. The activities of glyceraldehyde 3-phosphate DH and Lactate DH are linked metabolically. What happens to the lactate after a run?
64. In anaerobic yeast, pyruvate->ethanol Pyruvate is decarboxylated. Acetaldehyde is reduced.
65. Variations on a theme in alcoholic fermentation. Here also, there is no net oxidation reduction.
66. Enzyme Classification Dehydrogenase - oxidizes substrate using cofactors as electron acceptor or donor (pyruvate dehydrogenase) Reductase- adds electrons from some reduced cofactor (enoyl ACP reductase) Kinase- phosphorylates substrate (hexokinase) Hydrolases - uses water to cleave a molecule Phosphatase- hydrolyzes phosphate esters (glucose-6-phosphatase) Esterase (lipase)- hydrolyzes esters (those that act on lipid esters are lipases) (lipoprotein lipase) Thioesterases - hydrolyzes thioesters Thiolase- uses thiol to assist in forming thioester (β-ketothiolase) Isomerases- interconversions of isomers
69. Figure 6.12 Protein complex Electron carrier Inner mitochondrial membrane Electron flow Electron transport chain ATP synthase Electron Transport Chain
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71. Adding Up the ATP from Cellular Respiration Figure 6.14 Cytosol Mitochondrion Glycolysis Glucose 2 Pyruvic acid 2 Acetyl- CoA Krebs Cycle Electron Transport by direct synthesis by direct synthesis by ATP synthase Maximum per glucose:
72. Figure 6.13 Food Polysaccharides Fats Proteins Sugars Glycerol Fatty acids Amino acids Amino groups Glycolysis Acetyl- CoA Krebs Cycle Electron Transport