1. Carbohydrate metabolism
Chapter 3
Carbohydrate metabolism

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 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 catabolism of glucose to generate energy
STARCHY FOOD
α – AMYLASE ; MALTASES
Glucose
Glucose converted to glu-6-PO4
Start of cycle
Glycolysis in cytosol
Cycle : anaerobic
Aerobic condition; in mitochondria
2[Pyruvate+ATP+NADH]
Anaerobic condition
Pyruvate enters as AcetylcoA
- Krebs Cycle
- E transport chain
Lactic Acid fermentation in muscle.
Only in yeast/bacteria Anaerobic respiration or
Alcohol fermentation

6. GLYCOLYSIS
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7. Glycolysis 1st stage of glucose metabolism → glycolysis
An anaerobic process, yields 2 ATP (additional energy source)
Glucose will be metabolized via gycolysis; pyruvate as the end product
The pyruvate will be converted to lactic acid (muscles → liver)
Aerobic conditions: the main purpose is to feed pyruvate into TCA cycle for further rise of ATP

8. The breakdown of glucose to pyruvate as summarized:
Glucose (six C atoms) → 2 pyruvate (three C atoms)
2 ATP + 4 ADP + 2 Pi → 2 ADP + 4 ATP (phosphorylation)
Glucose + 2 ADP + 2 Pi → 2 Pyruvate + 2 ATP (Net reaction)
FIGURE 17.1 One molecule of glucose is converted to two molecules of pyruvate. Under aerobic conditions, pyruvate is oxidized to CO2 and H2O by the citric acid cycle (Chapter 19) and oxidative phosphorylation (Chapter 20). Under anaerobic conditions, lactate is produced, especially in muscle. Alcoholic fermentation occurs in yeast. The NADH produced in the conversion of glucose to pyruvate is reoxidized to NAD+ in the subsequent reactions of pyruvate.
Fig. 17-1, p.464

9. FIGURE 17.2 The glycolytic pathway.
Fig. 17-2, p.465

10. Louis Pasteur French biologist
did research on fermentation which led to important discoveries in microbiology and chemistry
Louis Pasteur (1822–1895). His research on fermentation led to important discoveries in microbiology and chemistry.

11. How 6-carbon glucose converted to the 3-carbon glyceraldehyde-3-phosphate?
Preparation phase
Step 1
Glucose is phosphorylated to give gluc-6-phosphate
p.467

12. FIGURE 17.3 In the first phase of glycolysis, five reactions convert a molecule of glucose to two molecules of glyceraldehyde-3-phosphate.
Fig. 17-3, p.468

13. FIGURE 17.3 In the first phase of glycolysis, five reactions convert a molecule of glucose to two molecules of glyceraldehyde-3-phosphate.

14. Table 17-1, p.469

15. FIGURE 17.4 A comparison of the conformations of hexokinase and the hexokinase–glucose complex.
Fig. 17-4, p.470

16. Glucose-6-phosphate isomerize to give fructose-6-phosphate Step 2
p.470a

17. Step 3
Fructose-6-phosphate is phosphorylated producing fructose-1,6-bisphosphate
p.470b

18. FIGURE 17.6 At high [ATP], phosphofructokinase behaves cooperatively, and the plot of enzyme activity versus [fructose-6-phosphate] is sigmoidal. High [ATP] thus inhibits PFK, decreasing the enzyme’s affinity for fructose-6-phosphate.
Fig. 17-6, p.471

19. Fructose-1,6-bisphosphate split into two 3-carbon fragments
Step 4
Fructose-1,6-bisphosphate split into two 3-carbon fragments
p.471a

20. Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate
Step 5
Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate
p.471b

21. How is glyceraldehyde-6-phosphate converted to pyruvate
Payoff phase
Step 6
Glyceraldehyde-6-phosphate is oxidized to 1,3-bisphosphoglycerate
p.472

22. FIGURE 17.7 The second phase of glycolysis.
Fig. 17-7, p.473

23. FIGURE 17.7 The second phase of glycolysis.

24. p.474a

25. FIGURE 17.8 Schematic view of the binding site of an NADH-linked dehydrogenase. There are specific binding sites for the adenine nucleotide portion of the coenzyme (shown in red to the right of the dashed line) and for the nicotinamide portion of the coenzyme (shown in yellow to the left of the dashed line), in addition to the binding site for the substrate. Specific interactions with the enzyme hold the substrate and coenzyme in the proper positions. Sites of interaction are shown as a series of pale green lines.
Fig. 17-8, p.475

26. Production of ATP by phosphorylation of ADP
Step 7
Production of ATP by phosphorylation of ADP
p.476

27. Phosphate group is transferred from C-3 to C-2
Step 8
Phosphate group is transferred from C-3 to C-2
p.477a

28. Dehydration reaction of 2-phosphoglycerate to phosphoenolpyruvate
Step 9
Dehydration reaction of 2-phosphoglycerate to phosphoenolpyruvate
p.477b

29. Step 10
Phosphoenolpyruvate transfers its phosphate group to ADP → ATP and pyruvate
p.478

30. Control points in glycolysis
FIGURE Control points in glycolysis.
Control points in glycolysis
Fig , p.479

31. How is pyruvate metabolized anaerobically?
Conversion of pyruvate to lactate in muscle
p.479

32. FIGURE 17.11 The recycling of NAD and NADH in anaerobic glycolysis.
Fig b, p.481

33. FIGURE 17.11 The recycling of NAD and NADH in anaerobic glycolysis.
Pyruvate decarboxylase
Fig a, p.481

34. FIGURE The structures of thiamine (vitamin B1) and thiamine pyrophosphate (TPP), the active form of the coenzyme.
Fig , p.482

35. Acetaldehyde + NADH → Ethanol + NAD+
Glucose + 2 ADP + 2 Pi + 2 H+ → 2 Ethanol + 2 ATP + 2 CO2 + 2 H2O
p.482

36. Carbohydrate metabolism
Chapter 3
(cont.)
Carbohydrate metabolism

37. 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
STEP 1
p.495

38. 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

39. FIGURE 18. 6 The pathways of gluconeogenesis and glycolysis
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).
STEP 2

40. 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?
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.

42. as 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.
when the cell needs ATP, glycolisys is more active
When there is little need for ATP, gluconeogenesis is more active
As energy store for next exercise
FIGURE 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.)
Fig , p.502

43. Cori cycle requires the net hydrolysis of two ATP and two GTP.
Gerty and Carl Cori, codiscoverers of the Cori cycle.

44. FIGURE 18. 13 Control of liver pyruvate kinase by phosphorylation
FIGURE 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.
Fig , p.503

45. 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
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.

46. FIGURE 19. 2 The structure of a mitochondrion
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.)
Fig. 19-2, p.513

47. FIGURE 19. 3 An overview of the citric acid cycle
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.

48. Steps 3,4,6 and 8 – oxidation reactions
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.
Fig. 19-3b, p.514

49. 5 enzymes make up the pyruvate dehydrogenase complex:
pyruvate dehydrogenase (PDH)
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase
Pyruvate dehydrogenase kinase
Pyruvate dehydrogenase phosphatase
Conversion of pyruvate to acetyl-CoA

50. Step 1
Formation of citrate
p.518

51. Step 2
Isomerization
Table 19-1, p.518

52. cis-Aconitate as an intermediate in the conversion of citrate to isocitrate
FIGURE 19.6 Three-point attachment to the enzyme aconitase makes the two -CH2-COO- ends of citrate stereochemically nonequivalent.
Fig. 19-6, p.519

54. Formation of α-ketoglutarate and CO2 – first oxidation
Step 3
Formation of α-ketoglutarate and CO2 – first oxidation
FIGURE 19.7 The isocitrate dehydrogenase reaction.
Fig. 19-7, p.521

55. Formation of succinyl-CoA and CO2 – 2nd oxidation
Step 4
Formation of succinyl-CoA and CO2 – 2nd oxidation
p.521

56. Formation of succinate
Step 5
Formation of succinate
p.522

57. Formation of fumarate – FAD-linked oxidation
Step 6
Formation of fumarate – FAD-linked oxidation
p.523a

58. Step 7
Formation of L-malate
p.524a

59. Regeneration of oxaloacetate – final oxidation step Step 8
p.524b

60. Krebs cycle produced: 6 CO2 2 ATP 6 NADH 2 FADH2 Fig. 19-8, p.526
FIGURE 19.8 Control points in the conversion of pyruvate to acetyl-CoA and in the citric acid cycle.
Krebs cycle produced:
6 CO2
2 ATP
6 NADH
2 FADH2
Fig. 19-8, p.526

61. Table 19-3, p.527

62. FIGURE 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.)
Fig , p.530

63. FIGURE 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.
Fig , p.531

64. FIGURE 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 )
Fig , p.533

65. FIGURE 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 )
Fig , p.535

66. Oxidative decarboxylation
Overall production from glycolysis, oxidative decarboxylation and TCA:
Oxidative decarboxylation
Glycolysis
TCA cycle -
2 ATP
2 NADH
6 NADH , 2 FADH2
2 CO2
2 Pyruvate
4 CO2
Electron transportation system