Ch03 cont.
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Carbohydrate metabolism involves the breakdown of glucose to generate energy through various pathways depending on the organism and environmental conditions. There are two main types of respiration: anaerobic respiration which includes glycolysis and fermentation, and aerobic respiration which includes oxidative decarboxylation of pyruvate, the citric acid cycle, and oxidative phosphorylation. Gluconeogenesis is the process of generating new glucose from non-carbohydrate precursors and occurs in the liver and kidneys. Glycogen is an energy storage molecule that is broken down to glucose through glycogenolysis or synthesized from glucose through glycogenesis, and its metabolism is regulated by insulin, glucagon, and epinephrine to maintain blood glucose levels.
![Brief overview of STARCHY
catabolism of FOOD
glucose to generate
α – AMYLASE ; MALTASES
energy
Glucose Glucose converted to glu-6-PO4
Start of cycle
Glycolysis in
Cycle : anaerobic cytosol
Aerobic condition;
2[Pyruvate+ATP+NADH] in mitochondria
Anaerobic condition Pyruvate enters as AcetylcoA
- Krebs Cycle
Lactic Acid fermentation in
muscle. - E transport chain
Only in yeast/bacteria
Anaerobic respiration or
Alcohol fermentation](https://image.slidesharecdn.com/ch03-cont-120926004102-phpapp01/85/Ch03-cont-5-320.jpg)
![ is the biosynthesis of new glucose from non-CHO precursors.
this glucose is as a fuel source by the brain, testes, erythrocytes and
kidney medulla
comprises of 9 steps and occurs in liver and kidney
the process occurs when quantity of glycogen have been depleted -
Used to maintain blood glucose levels.
Designed to make sure blood glucose levels are high enough to meet
the demands of brain and muscle (cannot do gluconeogenesis).
promotes by low blood glucose level and high ATP
inhibits by low ATP
occurs when [glu] is low or during periods of fasting/starvation, or
intense exercise
pathway is highly endergonic
*endergonic is energy consuming](https://image.slidesharecdn.com/ch03-cont-120926004102-phpapp01/85/Ch03-cont-7-320.jpg)
![REGULATION OF GLYCOGEN METABOLISM
Mobilization and synthesis of glycogen under hormonal control.
Three hormones involved:
1) Insulin
•51 a.a. protein made by β cells of pancreas.
•Secreted when [glucose] high --> increases rate of glucose transport into muscle and fat
via GLUT4 glucose transporters.
•Stimulates glycogen synthesis in liver.
2) Glucagon
•29 a.a. protein secreted by α cells of pancreas.
•Operational under low [glucose].
•Restores blood sugar levels by stimulating glycogen degradation.
3) Epinephrine
•Stimulates glycogen mobilization to glucose 1-phosphate --> glucose 6-phosphate.
•Increases rate of glycolysis in muscle and the amount of glucose in bloodstream.](https://image.slidesharecdn.com/ch03-cont-120926004102-phpapp01/85/Ch03-cont-44-320.jpg)
![Regulation of glycogen phosphorylase and glycogen synthase
•Reciprocal regulation.
•Glycogen synthase -P --> inactive form (b).
•Glycogen phosphorylase-P ---> active (a).
•When blood glucose is low, protein kinase A activated through hormonal action of
glucagon --> glycogen synthase inactivated and phosphorylase kinase activated -->
activates glycogen phosphorylase --> glycogen degradation occurs.
•Phosphorylase kinase also activated by increased [Ca2+] during muscle contraction.
•To reverse the same pathway involves protein phosphatases, which remove phosphate
groups from proteins --> dephosphorylates phosphorylase kinase and glycogen
phosphorylase (both inactivated), but dephosphorylation of glycogen synthase activates
this enzyme.
•Protein phosphatase-1 activated by insulin --> dephosphorylates glycogen synthase -->
glycogen synthesis occurs.
•In liver, glycogen phosphorylase a inhibits phosphatase-1 --> no glycogen synthesis can
occur.
•Glucose binding to protein phosphatase-1 activated protein phosphatase-1 --> it
dephosphorylates glycogen phosphorylase --> inactivated --> no glycogen degradation.
•Protein phosphatase-1 can also dephosphorylate glycogen synthase --> active.](https://image.slidesharecdn.com/ch03-cont-120926004102-phpapp01/85/Ch03-cont-45-320.jpg)
Ch03 cont.
- 2. Break-down of glucose to generate energy - Also known as Respiration. - Comprises of these different processes depending on type of organism: I. Anaerobic Respiration II. Aerobic Respiration
- 3. Anaerobic Respiration Comprises of these stages: glycolysis: glucose 2 pyruvate + NADH fermentation: pyruvate lactic acid or ethanol cellular respiration:
- 4. Aerobic Respiration Comprises of these stages: Oxidative decarboxylation of pyruvate Citric Acid cycle Oxidative phosphorylation/ Electron Transport Chain(ETC)
- 5. Brief overview of STARCHY catabolism of FOOD glucose to generate α – AMYLASE ; MALTASES energy Glucose Glucose converted to glu-6-PO4 Start of cycle Glycolysis in Cycle : anaerobic cytosol Aerobic condition; 2[Pyruvate+ATP+NADH] in mitochondria Anaerobic condition Pyruvate enters as AcetylcoA - Krebs Cycle Lactic Acid fermentation in muscle. - E transport chain Only in yeast/bacteria Anaerobic respiration or Alcohol fermentation
- 6. Gluconeogenesis Conversion of pyruvate to glucose Biosynthesis and the degradation of many important biomolecules follow different pathways There are three irreversible steps in glycolysis and the differences bet. glycolysis and gluconeogenesis are found in these reactions Different pathway, reactions and enzyme ST E P1 p.495
- 7. is the biosynthesis of new glucose from non-CHO precursors. this glucose is as a fuel source by the brain, testes, erythrocytes and kidney medulla comprises of 9 steps and occurs in liver and kidney the process occurs when quantity of glycogen have been depleted - Used to maintain blood glucose levels. Designed to make sure blood glucose levels are high enough to meet the demands of brain and muscle (cannot do gluconeogenesis). promotes by low blood glucose level and high ATP inhibits by low ATP occurs when [glu] is low or during periods of fasting/starvation, or intense exercise pathway is highly endergonic *endergonic is energy consuming
- 8. STEP 2
- 9. The oxalocetate formed in the mitochondria have two fates: - continue to form PEP - turned into malate by malate dehydrogenase and leave the mitochondria, have a reaction reverse by cytosolic malate dehydrogenase Reason?
- 11. Controlling glucose metabolism • found in Cori cycle • shows the cycling of glucose due to gycolysis in muscle and gluconeogenesis in liver • This two metabolic pathways are not active simultaneously. As energy store for • when the cell needs next exercise ATP, glycolisys is more active •When there is little need for ATP, gluconeogenesis is more active Fig. 18-12, p.502
- 12. Cori cycle requires the net hydrolysis of two ATP and two GTP. glu cos e + 2 NAD + + 2 ADP + 2 Pi → + 2 Pyruvate + 2 NADH + 4 H + 2 ATP + 2 H 2O + 2 Pyruvate + 2 NADH + 4 H + 4 ATP + 2GTP + 6 H 2O → Glu cos e + 2 NAD + + 4 ADP + 2GDP + 6 Pi 2 ATP + 2GTP + 4 H 2O → 2 ADP + 2GDP + 4 Pi
- 14. The Citric Acid cycle Cycle where 30 to 32 molecules of ATP can be produced from glucose in complete aerobic oxidation Amphibolic – play roles in both catabolism and anabolism The other name of citric acid cycle: Krebs cycle and tricarboxylic acid cycle (TCA) Takes place in mitochondria
- 15. Fig. 19-2, p.513
- 17. Steps 3,4,6 and 8 – oxidation reactions Fig. 19-3b, p.514
- 18. 5 enzymes make up the pyruvate dehydrogenase complex: pyruvate dehydrogenase (PDH) Conversion of pyruvate Dihydrolipoyl transacetylase to acetyl-CoA Dihydrolipoyl dehydrogenase Pyruvate dehydrogenase kinase Pyruvate dehydrogenase phosphatase
- 19. Step 1 Formation of citrate p.518
- 20. Step 2 Isomerization Table 19-1, p.518
- 21. cis-Aconitate as an intermediate in the conversion of citrate to isocitrate Fig. 19-6, p.519
- 23. Step 3 Formation of α- ketoglutarate and CO2 – first oxidation Fig. 19-7, p.521
- 24. Step 4 Formation of succinyl-CoA and CO2 – 2nd oxidation p.521
- 25. Step 5 Formation of succinate p.522
- 26. Step 6 Formation of fumarate – FAD-linked oxidation p.523a
- 27. Step 7 Formation of L-malate p.524a
- 28. Step 8 Regeneration of oxaloacetate – final oxidation step p.524b
- 29. Krebs cycle produced: • 6 CO2 • 2 ATP • 6 NADH • 2 FADH2 Fig. 19-8, p.526
- 35. Overall production from glycolysis, oxidative decarboxylation and TCA: Oxidative Glycolysis TCA cycle decarboxylation - 2 ATP 2 ATP 2 NADH 2 NADH 6 NADH , 2 FADH2 2 CO2 2 Pyruvate 4 CO2 Electron transportation system
- 37. Glycogen stored in muscle and liver cells. Important in maintaining blood glucose levels. Glycogen structure: α-1,4 glycosidic linkages with α-1,6 branches. Branches give multiple free ends for quicker breakdown or for more places to add additional units. Fig. 18-1, p.488
- 38. STEP 1 Glycogen phosphorylase STEP 2 Phosphoglucomutase
- 39. Fig. 18-2, p.489
- 40. Glycogen Synthesis •Not reverse of glycogen degradation because different enzymes are used. •About 2/3 of glucose ingested during a meal is converted to glycogen. •First step is the first step of glycolysis: hexokinase glucose --------------> glucose 6-phosphate •There are three enzyme-catalyzed reactions: phosphoglucomutase glucose 6-phosphate ---------------------> glucose 1-phosphate glucose 1-phosphate ---------------> UDP-glucose (activated form of glucose) glycogen synthase UDP-glucose ----------------------> glycogen •Glycogen synthase cannot initiate glycogen synthesis; requires preexisting primer of glycogen consisting of 4-8 glucose residues with α (1,4) linkage. •Protein called glycogenin serves as anchor; also adds 7-8 glucose residues. •Addition of branches by branching enzyme (amylo-(1,4 --> 1,6)- transglycosylase). •Takes terminal 7 glucose residues from nonreducing end and attaches it via α(1,6) linkage at least 4 glucose units away from nearest branch.
- 41. p.490
- 42. Fig. 18-3, p.491
- 43. Fig. 18-4, p.492
- 44. REGULATION OF GLYCOGEN METABOLISM Mobilization and synthesis of glycogen under hormonal control. Three hormones involved: 1) Insulin •51 a.a. protein made by β cells of pancreas. •Secreted when [glucose] high --> increases rate of glucose transport into muscle and fat via GLUT4 glucose transporters. •Stimulates glycogen synthesis in liver. 2) Glucagon •29 a.a. protein secreted by α cells of pancreas. •Operational under low [glucose]. •Restores blood sugar levels by stimulating glycogen degradation. 3) Epinephrine •Stimulates glycogen mobilization to glucose 1-phosphate --> glucose 6-phosphate. •Increases rate of glycolysis in muscle and the amount of glucose in bloodstream.
- 45. Regulation of glycogen phosphorylase and glycogen synthase •Reciprocal regulation. •Glycogen synthase -P --> inactive form (b). •Glycogen phosphorylase-P ---> active (a). •When blood glucose is low, protein kinase A activated through hormonal action of glucagon --> glycogen synthase inactivated and phosphorylase kinase activated --> activates glycogen phosphorylase --> glycogen degradation occurs. •Phosphorylase kinase also activated by increased [Ca2+] during muscle contraction. •To reverse the same pathway involves protein phosphatases, which remove phosphate groups from proteins --> dephosphorylates phosphorylase kinase and glycogen phosphorylase (both inactivated), but dephosphorylation of glycogen synthase activates this enzyme. •Protein phosphatase-1 activated by insulin --> dephosphorylates glycogen synthase --> glycogen synthesis occurs. •In liver, glycogen phosphorylase a inhibits phosphatase-1 --> no glycogen synthesis can occur. •Glucose binding to protein phosphatase-1 activated protein phosphatase-1 --> it dephosphorylates glycogen phosphorylase --> inactivated --> no glycogen degradation. •Protein phosphatase-1 can also dephosphorylate glycogen synthase --> active.
- 46. p.493
Editor's Notes
- #9: FIGURE 18.6 The pathways of gluconeogenesis and glycolysis. Species in blue, green, and pink shaded boxes indicate other entry points for gluconeogenesis (in addition to pyruvate).
- #10: FIGURE 18.9 Pyruvate carboxylase catalyzes a compartmentalized reaction. Pyruvate is converted to oxaloacetate in the mitochondria. Because oxaloacetate cannot be transported across the mitochondrial membrane, it must be reduced to malate, transported to the cytosol, and then oxidized back to oxaloacetate before gluconeogenesis can continue.
- #12: FIGURE 18.12 The Cori cycle. Lactate produced in muscles by glycolysis is transported by the blood to the liver. Gluconeogenesis in the liver converts the lactate back to glucose, which can be carried back to the muscles by the blood. Glucose can be stored as glycogen until it is degraded by glycogenolysis. (NTP stands for nucleoside triphosphate.)
- #13: Gerty and Carl Cori, codiscoverers of the Cori cycle.
- #14: FIGURE 18.13 Control of liver pyruvate kinase by phosphorylation. When blood glucose is low, phosphorylation of pyruvate kinase is favored. The phosphorylated form is less active, thereby slowing glycolysis and allowing pyruvate to produce glucose by gluconeogenesis.
- #15: FIGURE 19.1 The central relationship of the citric acid cycle to catabolism. Amino acids, fatty acids, and glucose can all produce acetyl-CoA in stage 1 of catabolism. In stage 2, acetyl-CoA enters the citric acid cycle. Stages 1 and 2 produce reduced electron carriers (shown here as e-). In stage 3, the electrons enter the electron transport chain, which then produces ATP.
- #16: FIGURE 19.2 The structure of a mitochondrion. (a) Colored scanning electron microscope image showing the internal structure of a mitochondrion (green, magnified 19,200 x). (b) Interpretive drawing of the scanned image. (c) Perspective drawing of a mitochondrion. (For an electron micrograph of mitochondrial structure, see Figure 1.13.)
- #17: FIGURE 19.3 An overview of the citric acid cycle. Note the names of the enzymes. The loss of CO2 is indicated, as is the phosphorylation of GDP to GTP. The production of NADH and FADH2 is also indicated.
- #18: FIGURE 19.3 An overview of the citric acid cycle. Note the names of the enzymes. The loss of CO2 is indicated, as is the phosphorylation of GDP to GTP. The production of NADH and FADH2 is also indicated.
- #22: FIGURE 19.6 Three-point attachment to the enzyme aconitase makes the two -CH2-COO - ends of citrate stereochemically nonequivalent.
- #24: FIGURE 19.7 The isocitrate dehydrogenase reaction.
- #30: FIGURE 19.8 Control points in the conversion of pyruvate to acetyl-CoA and in the citric acid cycle.
- #32: FIGURE 19.10 A summary of catabolism, showing the central role of the citric acid cycle. Note that the end products of the catabolism of carbohydrates, lipids, and amino acids all appear. (PEP is phosphoenolpyruvate; -KG is ketoglutarate; TA is transamination; is a multistep pathway.)
- #33: FIGURE 19.11 How mammals keep an adequate supply of metabolic intermediates. An anabolic reaction uses a citric acid cycle intermediate ( - ketoglutarate is transaminated to glutamate in our example), competing with the rest of the cycle. The concentration of acetyl-CoA rises and signals the allosteric activation of pyruvate carboxylase to produce more oxaloacetate. * Anaplerotic reaction. **Part of glyoxylate pathway.
- #34: FIGURE 19.12 Transfer of the starting materials of gluconeogenesis from the mitochondrion to the cytosol. Note that phosphoenolpyruvate (PEP) can be transferred from the mitochondrion to the cytosol, as can malate. Oxaloacetate is not transported across the mitochondrial membrane. (1 is PEP carboxykinase in mitochondria; 2 is PEP carboxykinase in cytosol; other symbols are as in Figure 19.10.)
- #35: FIGURE 19.15 A summary of anabolism, showing the central role of the citric acid cycle. Note that there are pathways for the biosynthesis of carbohydrates, lipids, and amino acids. OAA is oxaloacetate, and ALA is -aminolevulinic acid. Symbols are as in Figure 19.10.)
- #37: Control of carbohydrate metabolism is important in physical activity of all sorts.
- #38: FIGURE 18.1 The highly branched structure of glycogen makes it possible for several glucose residues to be released at once to meet energy needs. This would not be possible with a linear polymer. The red dots indicate the terminal glucose residues that are released from glycogen. The more branch points there are, the more of these terminal residues that are available at one time.
- #40: FIGURE 18.2 The mode of action of the debranching enzyme in glycogen breakdown. The enzyme transfers three (1 4)-linked glucose residues from a limit branch to the end of another branch. The same enzyme also catalyzes the hydrolysis of the (1 6)-linked residue at the branch point.
- #43: FIGURE 18.3 The reaction catalyzed by glycogen synthase. A glucose residue is transferred from UDPG to the growing end of a glycogen chain in an (1 4) linkage.
- #44: FIGURE 18.4 The mode of action of the branching enzyme in glycogen synthesis. A segment seven residues long is transferred from a growing branch to a new branch point, where an (1 6) linkage is formed.