Microbial catabolic activities are naturally selected by ...
Prentice Hall c2002Chapter 111 Fig 10.5 Overview of catabolic pathways.
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Transcript of Prentice Hall c2002Chapter 111 Fig 10.5 Overview of catabolic pathways.
Prentice Hall c2002 Chapter 11 1
Fig 10.5
• Overview of catabolic pathways
Prentice Hall c2002 Chapter 11 2
Fig 11.1• Catabolism of glucose via
glycolysis and the citric acid cycle
NADH, FADH2
NADH
Prentice Hall c2002 Chapter 11 3
Net reaction of glycolysis
• Two molecules of ATP are produced
• Two molecules of NAD+ are reduced to NADH
Glucose + 2 ADP + 2 NAD+ + 2 Pi
2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Converts: 1 glucose 2 pyruvate
+
Prentice Hall c2002 Chapter 11 4
Glycolysis can be divided into two stages
• Hexose stage: 2 ATP are consumed per glucose
• Triose stage: 4 ATP are produced per glucose
Net: 2 ATP produced per glucose
x2
Prentice Hall c2002 Chapter 11 5
Table 11.1
Prentice Hall c2002 Chapter 11 6
Fig 11.2
Transfer of a phosphorylgroup from ATP to glucose
enzyme: hexokinase
Isomerization of glucose 6-phosphateto fructose 6-phosphate
enzyme: glucose 6-phosphate isomerase
1
2
Prentice Hall c2002 Chapter 11 7
Transfer of a secondphosphoryl group from ATP to fructose 6-phosphate
enzyme: phosphofructokinase-1
Carbon 3 – Carbon 4bond cleavage, yielding twotriose phosphates
enzyme: aldolase
3
4
Prentice Hall c2002 Chapter 11 8
Prentice Hall c2002 Chapter 11 9
Prentice Hall c2002 Chapter 11 10
Enzyme 1. Hexokinase
• Transfers the -phosphoryl of ATP to glucose C-6 oxygen to generate glucose 6-phosphate
• Mechanism: attack of C-6 hydroxyl oxygen of glucose on the -phosphorous of MgATP2- displacing MgADP-
Fig 11.3
Prentice Hall c2002 Chapter 11 11
2. Glucose 6-Phosphate Isomerase
• Converts glucose 6-phosphate (an aldose) to fructose 6-phosphate (a ketose)
• Enzyme converts glucose 6-phosphate to open chain form in the active site
Fig 11.4
Prentice Hall c2002 Chapter 11 12
3. Phosphofructokinase-1 (PFK-1)
• Catalyzes transfer of a phosphoryl group from ATP to the C-1 hydroxyl group of fructose 6-phosphate to form fructose 1,6-bisphosphate (F1,6BP)
• PFK-1 is metabolically irreversible and a critical regulatory point for glycolysis in most cells (PFK-1 is the first committed step of glycolysis)
Prentice Hall c2002 Chapter 11 13
4. Aldolase
• Aldolase cleaves the hexose fructose 1,6-bisphosphate into two triose phosphates: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate
Prentice Hall c2002 Chapter 11 14
5. Triose Phosphate Isomerase
• Conversion of dihydroxyacetone phosphate into glyceraldehyde 3-phosphate
Prentice Hall c2002 Chapter 11 15
Fig 11.6 Fate of carbon atoms from hexose stage to triose stage
Prentice Hall c2002 Chapter 11 16
6. Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)
• Conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate (1,3BPG)
• Molecule of NAD+ is reduced to NADH
Prentice Hall c2002 Chapter 11 17
Fig 11.7
• Mechanism of Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)
Prentice Hall c2002 Chapter 11 18
Fig 11.7 (continued)
(2)(3)
Prentice Hall c2002 Chapter 11 19
Fig 11.7 (continued)
Prentice Hall c2002 Chapter 11 20
Box 11.2 Arsenate (AsO43-) poisoning
• Arsenate can replace Pi as a substrate for glyceraldehyde 3-phosphate dehydrogenase
• Arseno analog which forms is unstable
Prentice Hall c2002 Chapter 11 21
7. Phosphoglycerate Kinase
• Transfer of phosphoryl group from the energy-rich 1,3-bisphosphoglycerate to ADP yields ATP and 3-phosphoglycerate
• Uses uses the high-energy phosphate of 1,3-bisphosphoglycerate to form ATP from ADP
Prentice Hall c2002 Chapter 11 22
8. Phosphoglycerate Mutase
• Catalyzes transfer of a phosphoryl group from one part of a substrate molecule to another
• Reaction occurs without input of ATP energy
Prentice Hall c2002 Chapter 11 23
9. Enolase: 2-phosphoglycerate to phosphoenolpyruvate (PEP)
• Elimination of water (dehydration) yields PEP
• PEP has a very high phosphoryl group transfer potential because it exists in its unstable enol form
Prentice Hall c2002 Chapter 11 24
10. Pyruvate Kinase
• Metabolically irreversible reaction
Prentice Hall c2002 Chapter 11 25
Fates of pyruvate
• For centuries, bakeries and breweries have exploited the conversion of glucose to ethanol and CO2 by glycolysis in yeast
Prentice Hall c2002 Chapter 11 26
Metabolism of Pyruvate
1. Aerobic conditions: pyruvate is oxidized to acetyl CoA, which enters the citric acid cycle for further oxidation
2. Anaerobic conditions (microorganisms): pyruvate is converted to ethanol
3. Anaerobic conditions (muscles, red blood cells): pyruvate is converted to lactate
Prentice Hall c2002 Chapter 11 27
Fig 11.10
• Three major fates of pyruvate
Prentice Hall c2002 Chapter 11 28
Fig 11.11
• Anaerobic conversion of pyruvate to ethanol (yeast - anaerobic)
• Two enzymes required:
(1) Pyruvate decarboxylase
(2) Alcohol dehydrogenase
Prentice Hall c2002 Chapter 11 29
Reduction of Pyruvate to Lactate (muscles - anaerobic)
• Muscles lack pyruvate dehydrogenase and cannot produce ethanol from pyruvate
• Muscle lactate dehydrogenase converts pyruvate to lactate
• This reaction regenerates NAD+ for use by glyceraldehyde 3-phosphate dehydrogenase in glycolysis
• Lactate formed in skeletal muscles during exercise is transported to the liver
• Liver lactate dehydrogenase can reconvert lactate to pyruvate
• Lactic acidosis can result from insufficient oxygen (an increase in lactic acid and decrease in blood pH)
Prentice Hall c2002 Chapter 11 30
Reduction of pyruvate to lactate
Glucose + 2 Pi2- + 2 ADP3-
2 Lactate- + 2 ATP4- + 2 H2O
Prentice Hall c2002 Chapter 11 31
Metabolically Irreversible Steps of Glycolysis
• Enzymes not reversible:Reaction 1 - hexokinaseReaction 3 - phosphofructokinaseReaction 10 - pyruvate kinase
• These steps are metabolically irreversible, and these enzymes are regulated
• All other steps of glycolysis are near equilibrium in cells and not regulated
Prentice Hall c2002 Chapter 11 32
Regulation of Glycolysis
1. When ATP is needed, glycolysis is activated
• Inhibition of phosphofructokinase-1 is relieved.
• Pyruvate kinase is activated.
2. When ATP levels are sufficient, glycolysis activity decreases
• Phosphofructokinase-1 is inhibited.
• Hexokinase is inhibited.
Prentice Hall c2002 Chapter 11 33
Fig 11.13Glucose transport
into the cell
Prentice Hall c2002 Chapter 11 34
Fig 11.14 Regulation of glucose transport
• Glucose uptake into skeletal and heart muscle and adipocytes by GLUT 4 is stimulated by insulin
Prentice Hall c2002 Chapter 11 35
Regulation of Hexokinase
• Hexokinase reaction is metabolically irreversible
• Glucose 6-phosphate (product) levels increase when glycolysis is inhibited at sites further along in the pathway
• Glucose 6-phosphate inhibits hexokinase.
Prentice Hall c2002 Chapter 11 36
Regulation of Phosphofructokinase-1 (PFK-1)
• ATP is a substrate and an allosteric inhibitor of PFK-1
• High concentrations of ADP and AMP allosterically activate PFK-1 by relieving the ATP inhibition.
• Elevated levels of citrate (indicate ample substrates for citric acid cycle) also inhibit Phospofructokinase-1
Prentice Hall c2002 Chapter 11 37
Fig 11.16 Regulation of Phosphofructokinase-1 by ATP and AMP
• AMP relieves ATP inhibition of PFK-1
Prentice Hall c2002 Chapter 11 38
Regulation of PFK-1 by Fructose 2,6-bisphosphate (F2,6BP)
• Fructose 2,6-bisphosphate is formed from Fructose 6-phosphate by the enzyme phosphofructokinase-2 (PFK-2)
• Fig 11.17 Fructose 2,6-bisphosphate
Prentice Hall c2002 Chapter 11 39
Formation and hydrolysis of Fructose 2,6-bisphosphate
Prentice Hall c2002 Chapter 11 40
Fig. 11.18
• Effect of glucagon on liver glycolysis
Prentice Hall c2002 Chapter 11 41
Regulation of Pyruvate Kinase (PK)
• Pyruvate Kinase is allosterically activated by Fructose 1,6-bisphosphate, and inhibited by ATP
• The hormone glucagon stimulates protein kinase A, which phosphorylates Pyruvate Kinase, converting it to a less active form.
Prentice Hall c2002 Chapter 11 42
Other Sugars Can Enter Glycolysis
• Glucose is the main metabolic fuel in most organisms
• Other sugars convert to glycolytic intermediates
• Fructose and sucrose (contains fructose) are major sweeteners in many foods and beverages
• Galactose from milk lactose (a disaccharide)
• Mannose from dietary polysaccharides, glycoproteins
Prentice Hall c2002 Chapter 11 43
Fructose Is Converted to Glyceraldehyde 3-Phosphate
Fig 11.21
Prentice Hall c2002 Chapter 11 44
Galactose is Converted to Glucose 1-Phosphate
Fig 11.22
Prentice Hall c2002 Chapter 11 45
Mannose is Converted to Fructose 6-Phosphate
Prentice Hall c2002 Chapter 11 46
Formation of 2,3-Bisphosphoglycerate in Red Blood Cells
• 2,3-Bisphosphoglycerate (2,3BPG) allosterically regulates hemoglobin oxygenation (red blood cells)
• Erythrocytes contain bisphosphoglycerate mutase which forms 2,3BPG from 1,3BPG
• In red blood cells about 20% of the glycolytic flux is diverted for the production of the important oxygen regulator 2,3BPG
Prentice Hall c2002 Chapter 11 47
Fig 11.24
• Formation of 2,3BPG in red blood cells
Prentice Hall c2002 Chapter 11 48
Feedback inhibition
• Product of a pathway controls the rate of its own synthesis by inhibiting an enzyme catalyzing an early step
Feed-forward activation
• Metabolite early in the pathway activates an enzyme further down the pathway