glycolysis anaerobic degradation of glucose to yield lactate or ethanol and co 2
TRANSCRIPT
![Page 1: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/1.jpg)
Glycolysis
Anaerobic degradation of glucose to yield lactate
or ethanol and CO2
![Page 2: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/2.jpg)
Learning Objectives
• Sequence of Reactions
– Metabolites
– Enzymes
• Enzyme Mechanisms
• Energetics
• Regulation
![Page 3: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/3.jpg)
Overview of Glycolysis
Glucose (C6) —> 2 Pyruvate (C3)
2 ADP + 2 Pi —> 2 ATP
![Page 4: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/4.jpg)
Figure 15-1
Glycolysis
![Page 5: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/5.jpg)
Stage I of Glycolysis(Energy Investment)
2X
![Page 6: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/6.jpg)
Summary of Stage I
Glucose + 2 ATP ——> 2 GA3P + 2 ADP + 2 H+
![Page 7: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/7.jpg)
Stage II of Glycolysis(Energy Recovery)
Substrate Level Phosphorylation
Substrate Level Phosphorylation
—> Serine, Cysteine and Glycine
—> Aromatic Amino Acids
—> Alanine
![Page 8: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/8.jpg)
Summary of Stage II
2 GA3P + 2 NAD+ + 4 ADP + 2 Pi
2 Pyruvate + 2 NADH + 2 H+ + 4 ATP
![Page 9: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/9.jpg)
Summary of Glycolysis
Glucose + 2 NAD+ + 2 ADP + 2 Pi
2 Pyruvate + 2 NADH + 2 H+ + 2 ATP
NOTE: NAD+ must be regenerated!
![Page 10: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/10.jpg)
Reactions of Glycolysis
Stage I
![Page 11: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/11.jpg)
Hexokinase(First Use of ATP)
O
CH2OH
OH
OH
OHHO
O
CH2OPO3
OH
OH
OHHO
-D-glucose–6–P(G6P)
-D-glucose(Glc)
ATP ADP
Mg2+
2–
NOTE: Lack of Specificity
Go’ (kJ/mol) G (kJ/mol) Glucose + Pi G-6-P + H2O 13.8 20.5ATP + H2O ADP + Pi -30.5 -54.4
Glucose + ATP G-6-P + ADP -16.7 -33.9
![Page 12: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/12.jpg)
Page 489
Role of Mg2+
![Page 13: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/13.jpg)
Figure 15-2
Substrate-induced Conformational Changes in
Yeast Hexokinase
![Page 14: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/14.jpg)
Results of Conformational Change
• Formation of ATP binding site
• Exclusion of water
• Increased nucleophilicity of CH2OH
• Proximity effect
![Page 15: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/15.jpg)
Regulation of Hexokinase
Inhibition by glucose-6-P
Impermeability
![Page 16: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/16.jpg)
Hexokinase versus Glucokinase
• Hexokinase (all tissues)– Non-specific
– KM = ~100 µM
– Inhibited by glucose-6-P
• Glucokinase (primarily in liver)– Specific
– KM = ~10 mM
– Not inhibited by glucose-6-P
![Page 17: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/17.jpg)
Functional Rationale
• Most tissues: metabolize blood glucose which enters cells– Glc-6-P impermeable to cell membrane
– Product inhibition
• Liver: maintain blood glucose– High blood glucose: glycogen– Low blood glucose: glycolysis
![Page 18: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/18.jpg)
Figure 22-4
Hexokinase versus Glucokinase
![Page 19: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/19.jpg)
Metabolism of Glucose-6-P
Glucose-6-P Fructose-6-P Glycolysis
Glycogen
Pentose-P Pathway (NADPH)
Regulation!
![Page 20: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/20.jpg)
Phosphoglucose Isomerase
Go’ (kJ/mol) G (kJ/mol) Glucose-6-phosphate Fructose-6-phosphate 2.2 -1.4
![Page 21: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/21.jpg)
Reaction Mechanism of Phosphoglucose Isomerase
![Page 22: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/22.jpg)
Figure 15-3 part 1
Reaction Mechanism of Phosphoglucose Isomerase
(Substrate Binding)
![Page 23: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/23.jpg)
Figure 15-3 part 2
Reaction Mechanism of Phosphoglucose Isomerase(Acid-Catalyzed Ring Opening)
![Page 24: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/24.jpg)
Figure 15-3 part 3
Reaction Mechanism of Phosphoglucose Isomerase(Formation of cis-enediolate
Intermediate)
![Page 25: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/25.jpg)
Figure 15-3 part 4
Reaction Mechanism of Phosphoglucose Isomerase
(Proton Transfer)
![Page 26: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/26.jpg)
Figure 15-3 part 5
Reaction Mechanism of Phosphoglucose Isomerase(Base-Catalyzed Ring Closure)
![Page 27: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/27.jpg)
Figure 15-3 part 1
Reaction Mechanism of Phosphoglucose Isomerase
(Product Release)
![Page 28: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/28.jpg)
Phosphofructokinase(Second Use of ATP)
NOTE: bisphosphate versus diphosphate
Go’ (kJ/mol) G (kJ/mol) F-6-P + Pi F-1,6-bisP + H2O 16.3 36.0ATP + H2O ADP + Pi -30.5 -54.4
F-6-P + ATP F-1,6-bisP + ADP -14.2 -18.8
![Page 29: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/29.jpg)
Characteristics of Reaction Catalyzed by PFK
• Rate-determining reaction
• Reversed by Fructose-1,6-bisphosphatase
• Mechanism similar to Hexokinase
![Page 30: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/30.jpg)
Regulatory Properties of PFK
• Main control point in glycolysis
• Allosteric enzyme– Positive effectors
•AMP•Fructose-2,6-bisphosphate
– Negative effectors•ATP•Citrate
![Page 31: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/31.jpg)
Page 558
-D-Fructose-2,6-Bisphosphate
![Page 32: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/32.jpg)
Formation and Degradation of -D-Fructose-2,6-bisP
High glucose
Low glucose
![Page 33: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/33.jpg)
Aldolase
4
5
6
1
2
3
Carbon #from glucose
Go’ (kJ/mol) G (kJ/mol) F-1,6-bisP GAP + DHAP 23.8 ~0
![Page 34: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/34.jpg)
Figure 15-4
Mechanism of Base-Catalyzed Aldol Cleavage
NOTE: requirement for C=O at C2
Rationale for Phosphoglucose Isomerase
![Page 35: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/35.jpg)
Enzymatic Mechanism of Aldolase
![Page 36: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/36.jpg)
Figure 15-5 part 1
Enzymatic Mechanism of Aldolase
(Substrate Binding)
![Page 37: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/37.jpg)
Figure 15-5 part 2
Enzymatic Mechanism of Aldolase
(Schiff Base (imine) Formation)
![Page 38: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/38.jpg)
Figure 15-5 part 3
Enzymatic Mechanism of Aldolase
(Aldol Cleavage)
![Page 39: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/39.jpg)
Figure 15-5 part 4
Enzymatic Mechanism of Aldolase
(Tautomerization and Protonation)
![Page 40: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/40.jpg)
Figure 15-5 part 5
Enzymatic Mechanism of Aldolase
(Schiff Base Hydrolysis and Product Release)
![Page 41: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/41.jpg)
Triose Phosphate Isomerase
CHO
CHOH
CH2OP
Glyceraldehyde-3-P(GA3P)
CH2OH
C
CH2OP
O
Dihydroxyacetone-P(DHAP)
Go’ (kJ/mol) G (kJ/mol) DHAP GAP 7.5 ~0
![Page 42: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/42.jpg)
Part 494
Enzymatic Mechanism ofTriose Phosphate Isomerase
![Page 43: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/43.jpg)
Part 494
Transition State Analog Inhibitors of
Triose Phosphate Isomerase
![Page 44: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/44.jpg)
Figure 15-7
Schematic Diagram of the First Stage of
Glycolysis
![Page 45: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/45.jpg)
Summary of Stage I
Glucose + 2 ATP ——> 2 GA3P + 2 ADP + 2 H+
![Page 46: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/46.jpg)
Reactions of Glycolysis
Stage II
![Page 47: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/47.jpg)
Glyceraldehyde-3-P Dehydrogenase
GAPDHCHO
CHOH
CH2OP
Glyceraldehyde-3-P(GA3P)
+ NAD+ Pi+
COOP
CHOH
CH2OP
+ NADH H++
1,3-Bisphosphoglycerate(BPG)
3,4
2,5
1,6
Go’ (kJ/mol) G (kJ/mol) GAP + NAD+ H2O 3-PG + NADH + H+ -43.1 36.03PG + Pi 1,3-BPG + H2O 49.4 -54.4
GAP + NAD+ + Pi 1,3-BPG + NADH + H+ 6.3 -18.8
![Page 48: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/48.jpg)
Acylphosphate
C
CHOH
CH2OP
1,3-Bisphosphoglycerate(BPG)
O OP
R C OP
O
Acylphosphate("high energy")
![Page 49: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/49.jpg)
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase
![Page 50: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/50.jpg)
Figure 15-9 part 1
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase(Substrate Binding)
![Page 51: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/51.jpg)
Figure 15-9 part 2
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase(Thiol Addition)
![Page 52: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/52.jpg)
Figure 15-9 part 3
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase(Dehydrogenation)
![Page 53: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/53.jpg)
Figure 15-9 part 4
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase(Phosphate Binding)
![Page 54: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/54.jpg)
Figure 15-9 part 5
Enzymatic Mechanism ofGlyceraldehyde-3-P
Dehydrogenase(Product Release)
![Page 55: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/55.jpg)
2,3-bisphosphoglycerate
Rxn #8
Rxn #7
Rxn #6
Rxns #1-5 Hemoglobinregulation
Pyruvate kinase
Pyruvate
Rxn #9
Rxn #10
![Page 56: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/56.jpg)
Glycolysis deficiencies affect oxygen delivery
![Page 57: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/57.jpg)
Phosphoglycerate Kinase
Formation of first ATPs
Substrate-level Phosphorylation
![Page 58: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/58.jpg)
Figure 15-10
Yeast Phosphoglycerate Kinase
![Page 59: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/59.jpg)
Coupled Reactions
GA3P + NAD+ + H2O 3PGA + NADH + H+
3PGA + Pi 1,3BPG + H2O
GA3P + NAD+ + Pi
² Go' = –43.1 kJ / mol
² Go' = +49.4 kJ / mol
² Go' = +6.3 kJ / mol1,3BPG + NADH + H+
1,3BPG + ADP 3PGA + ATP ² Go' = –18.8 kJ / mol
GA3P + NAD+ + ADP + Pi3PGA + ATP + NADH + H+ ² Go' = –12.5 kJ /mol
G = ~0
![Page 60: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/60.jpg)
Substrate Channeling
![Page 61: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/61.jpg)
Phosphoglycerate Mutase
Go’ (kJ/mol) G (kJ/mol) 3-PGA 2-PGA 4.4 ~0
![Page 62: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/62.jpg)
Page 500
Phosphohistidine Residue inPhosphoglycerate Mutase
![Page 63: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/63.jpg)
Enzymatic Mechanism ofPhosphoglycerate Mutase
![Page 64: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/64.jpg)
Figure 15-12 part 1
Enzymatic Mechanism ofPhosphoglycerate Mutase
(Substrate Binding)
![Page 65: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/65.jpg)
Figure 15-12 part 2
Enzymatic Mechanism ofPhosphoglycerate Mutase(Phosphorylation of Substrate)
![Page 66: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/66.jpg)
Figure 15-12 part 3
Enzymatic Mechanism ofPhosphoglycerate Mutase(Phosphorylation of Enzyme)
![Page 67: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/67.jpg)
Figure 15-12 part 4
Enzymatic Mechanism ofPhosphoglycerate Mutase
(Product Release)
![Page 68: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/68.jpg)
Enolase
Formation of “high energy” intermediate
Inhibition by F–
Go’ (kJ/mol) G (kJ/mol) 2-PGA PEP -3.2 -2.4
![Page 69: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/69.jpg)
Pyruvate Kinase
Formation of second ATPs
Substrate-level Phosphorylation
Go’ (kJ/mol) G (kJ/mol) PEP + H2O Pyruvate + Pi -61.9 ADP + Pi ATP + H2O 30.5
PEP + ADP Pyruvate + ATP -31.4 -16.7
![Page 70: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/70.jpg)
Figure 15-13
Enzymatic Mechanism of Pyruvate Kinase
![Page 71: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/71.jpg)
Figure 15-14
Hydrolysis of PEP
![Page 72: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/72.jpg)
Regulatory Properties ofPyruvate Kinase
• Secondary control point in glycolysis
• Allosteric enzyme– Positive effectors
•ADP•Fructose-1,6-bisphosphate
– Negative effectors•ATP (energy charge)•Acetyl-Coenzyme A
![Page 73: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/73.jpg)
Figure 15-15
Summary of Second Stage
of Glycolysis
![Page 74: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/74.jpg)
Summary of Stage II
2 GA3P + 2 NAD+ + 4 ADP + 2 Pi
2 Pyruvate + 2 NADH + 2 H+ + 4 ATP
![Page 75: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/75.jpg)
Summary of Glycolysis
Glucose + 2 NAD+ + 2 ADP + 2 Pi
2 Pyruvate + 2 NADH + 2 H+ + 2 ATP
NOTE: NAD+ must be regenerated!
![Page 76: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/76.jpg)
Figure 15-16
Metabolic Fates of Pyruvate
![Page 77: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/77.jpg)
Recycling of NADH
Anaerobic Fate of Pyruvate
![Page 78: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/78.jpg)
Role of Anaerobic Glycolysis in Skeletal
Muscle
![Page 79: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/79.jpg)
Homolactate Fermentation
NADH + H+ NAD+
LactateLactate
Dehydrogenase
Pyruvate
![Page 80: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/80.jpg)
Page 505
Lactate Dehydrogenase
![Page 81: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/81.jpg)
Mechanismof
LactateDehydrogenase
![Page 82: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/82.jpg)
Summary of Anaerobic Glycolysis
Glucose + 2 ADP + 2 Pi
2 Lactate + 2 ATP + 2 H2O + 2 H+
![Page 83: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/83.jpg)
Energetics of Fermentation
Glucose ——> 2 Lactate
Glucose + 6 O2 ——> 6 CO2 + 6 H2O
∆Go’ = -200 kJ/mol
∆Go’ = -2866 kJ/mol
Most of the energy of glucose is still available following glycolysis!
![Page 84: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/84.jpg)
Alcoholic Fermentation
CO2 NADH + H+ NAD+
Pyruvate EthanolAlcohol
Dehydrogenase
AcetaldehydePyruvate
Decarboxylase
![Page 85: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/85.jpg)
Figure 15-18
Alcoholic Fermentation
![Page 86: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/86.jpg)
Figure 15-18 part 1
Pyruvate Decarboxylase
![Page 87: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/87.jpg)
Page 507
Thiamin Pyrophosphate
Thiamine = Vitamin B1
![Page 88: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/88.jpg)
Figure 15-20
Mechanism ofPyruvate Decarboxylase
![Page 89: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/89.jpg)
Figure 15-20 part 1
Mechanism ofPyruvate Decarboxylase
(Nucleophilic Attack)
![Page 90: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/90.jpg)
Figure 15-20 part 2
Mechanism ofPyruvate Decarboxylase
(CO2 Elimination)
![Page 91: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/91.jpg)
Figure 15-20 part 3
Mechanism ofPyruvate Decarboxylase(Protonation of Carbanion)
![Page 92: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/92.jpg)
Figure 15-20 part 4
Mechanism ofPyruvate Decarboxylase
(Product Release)
![Page 93: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/93.jpg)
Figure 15-18 part 2
Alcohol Dehydrogenase
![Page 94: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/94.jpg)
Page 509
Mechanism ofAlcohol Dehydrogenase
![Page 95: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/95.jpg)
Regulation of Glycolysisand Gluconeogenesis
![Page 96: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/96.jpg)
Table 15-1
Free Energy Changes of Glycolytic Reactions
![Page 97: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/97.jpg)
Figure 15-21
Diagram of Free Energy Changes in Glycolysis
![Page 98: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/98.jpg)
Regulatory Properties of Hexokinase
Inhibition by glucose-6-P
![Page 99: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/99.jpg)
Metabolism of Glucose-6-P
Glucose-6-P Fructose-6-P Glycolysis
Glycogen
Pentose-P Pathway (NADPH)
Regulation!
![Page 100: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/100.jpg)
Regulatory Properties ofPhosphofructokinase
• Main control point in glycolysis
![Page 101: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/101.jpg)
Figure 15-23
Regulation of Phosphofructokinase
![Page 102: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/102.jpg)
Regulatory Properties ofPyruvate Kinase
• Secondary control point in glycolysis
• Allosteric enzyme– Positive effectors
•ADP•Fructose-1,6-bisphosphate
– Negative effectors•ATP (energy charge)•Acetyl-Coenzyme A
![Page 103: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/103.jpg)
Gluconeogenesis
![Page 104: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/104.jpg)
Necessity of Glucose-6-P and Glucose
Glucose-6-P Fructose-6-P Glycolysis
Glycogen
Pentose-P Pathway (NADPH)
Glucose
![Page 105: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/105.jpg)
Glycolysisand
Gluconeogenesis
![Page 106: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/106.jpg)
Glycolysis and Gluconeogenesis
![Page 107: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/107.jpg)
Figure 16-21
Glycolysisand
Gluconeogenesis
![Page 108: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/108.jpg)
Figure 16-21
Glycolysis and Gluconeogenesis
![Page 109: Glycolysis Anaerobic degradation of glucose to yield lactate or ethanol and CO 2](https://reader035.vdocument.in/reader035/viewer/2022081508/56649efa5503460f94c0b80c/html5/thumbnails/109.jpg)
Coordinated Control of Glycolysis and Gluconeogenesis