Review Sessions for MT 1
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1 Review Sessions for MT 1 FRI (4/17): Mon (4/20): Kleiber all, 5-7 p.m. Kleiber all, 5-7 p.m. See ESSETIALS for MIDTERM 1 Problem sets and Midterms of 2008 and 2007 posted on the real 103 website (My UCDavis)
2 MIDTERM 1 ext Tuesday (4/21 from 1:40 3:00 p.m.) Seating Assignments (last name initial) (A-) Med Sci C 180 (I-Z) 198 Young all Bring a calculator supporting log functions!
3 Lecture 6 Degradation of other carbohydrates Pyruvate Dehydrogenase Complex (PD) Co-Factors, Reactions, Enzymes
4 The Powertrain of uman Metabolism (verview) CARBYDRATES PRTEIS LIPIDS Glucose Amino acids Fatty acids xaloacetate aerobic 2 Glycogen Glucose-6-P Pyruvate Acetyl-CoA AD ATP Glycolysis C 2 2 anaerobic Lactate Ketone bodies Ribose-5-P Cholesterol ADP AD p. 21
5 The Powertrain of uman Metabolism (verview) CARBYDRATES PRTEIS LIPIDS Sucrose Lactose Fructose Mannose Glycerol Galactose Starch Glucose xaloacetate Amino acids Fatty acids aerobic 2 Glycogen Glucose-6-P Pyruvate Acetyl-CoA AD ATP Glycolysis C 2 2 anaerobic Lactate Ketone bodies Ribose-5-P Cholesterol ADP AD p. 21
6 ydrolysis of Sucrose and Lactose C 2 glucosyl Sucrose 2 C C 2 fructosyl glucose (α1 β2) fructose Sucrose + 2 Glu + Fru Enzyme (ydrolase( ydrolase): Invertase (saliva, small intestines) p. 34
7 C 2 glucosyl Lactose C 2 galactosyl galactose (β1 4) glucose Lactose + 2 Gal + Glu Enzyme (ydrolase( ydrolase): Lactase (babies, weening animals) Lactose Intolerance p. 34
8 Metabolism of Fructose, Mannose, and Glycerol A. Fructose C 2 C 2 ATP 1 ADP C 2 C 2 P 2-3 Fructose F-6-P R C 2 C 2 Fructose ATP 14 ADP C 2 P 2-3 C 2 F-1-P 15 C 2 P 3 2- C 2 + C C 2 Dihydroxyacetone-P (DAP) ATP 16 ADP C C 2 P 3 2- Glyceraldehyde GA-3-P p. 35
9 B. Mannose C C ATP ADP C C 2 C 2 P C 2 P 3 Mannose Mannose-6-P (M-6-P) F-6-P p. 35
10 C. Glycerol C 2 C 2 Glycerol ATP 17 C 2 ADP C 2 P 2-3 Glycerol-3-P AD + 18 AD + + C 2 2- C 2 P 3 DAP p. 35
11 Enzymes for Converting ther Carbohydrates into Intermediates of Glycolysis ydrolases (di-, oligo-, and polysaccharides) Kinases (phosphotransferases; phosphorylation ) Isomerases (ketol isomerases, epimerases, mutases) Dehydrogenases (AD-dependent)
12 Metabolism of Galactose 23 UMP~P-Glc UMP~P-Gal UMP~P = UDP Galactose (Gal) Gal-1-P Glc-1-P p. 36
13 C C 2 C 2 ATP 21 ADP C 2 Metabolism of Galactose P 3 2- α-d-galctose α-d-gal-1-p C 2 P - P - 23 UDP-Glc 22 C 2 P - P - UDP-Gal C 2 α-d-glc-1-p P 3 2- p. 36
14 C 2 α-d-glc-1-p P 3 2- Metabolism of Galactose 24 Phosphoglucomutase 2- C 2 P 3 α-d-glc-6-p p. 36
15 Source of UDP-Glucose C 2 P 2-3 α-d-glc-1-p + - P - P - P - UTP 25 - P - P - - Pyrophosphate (PPi) + C 2 P - UDP-Glc P x Phosphate (Pi) p. 37
16 Degradation of Polysaccharides (Starch, Glycogen)
17 Digestive Tract Dietary Polysaccharides (Starch, Glycogen) Liver, Skeletal Muscles Intracellular Polysaccharides (Glycogen Reserve) ydrolysis (unregulated) Synthesis (ATP-dep.) Phosphorolysis (highly regulated) Glucose Glucose Glc-1-P (Glycolysis) Blood Glucose
18 Structure of Glycogen and Starch 6 C 2 C 2 C C 2 (α1 4) linkages C 2 C 2 (α1 4) linkages C 2 (α1 6) branch point 6C 2 C 2 C 2 C p. 38
19 p. 38 Structure of Glycogen and Starch
20 Starch Grains in Sweet Potato Tuber Cells mse.iastate.edu/images/microscopy/
21 ydrolysis of Dietary Starch and Glycogen β-amylase β-amylase β-amylase (exoglucosidase, plants) α(1 6) Glucosidase (debranching enzyme) β-amylase α-amylase (endoglucosidase) 2 0 (all glucosidases) Glc C Glc Maltase Maltose Glc (α1 4) Glc p. 39
22 Digestive Tract Dietary Polysaccharides (Starch, Glycogen) Liver, Skeletal Muscles Intracellular Polysaccharides (Glycogen Reserve) ydrolysis (unregulated) Synthesis (ATP-dep.) Phosphorolysis (highly regulated) Glucose Glucose Glc-1-P (Glycolysis) Blood Glucose
23 E P A T C Y T E Glycogen Granules (black) online-media. uni-marburg.de
24 Glycogen Granules in Muscle Fibers (white)
25 Phosphorolysis of Intracellular Glycogen on-reducing ends α1,4 linkages 4' 3' 2' Branch point one α1,6 linkage Reducing end 1' P 4 3- (Pi)...linked to protein Glycogen phosphorylase (or Starch phosphorylase) 11 Glc-1-P C 2 2- P 3 Limit dextrin 4' 3' 2' 1' α-(1,6) linkage linked to protein p. 40
26 Limit dextrin 4' 3' 2' 1' α-(1,6) linkage linked to protein Debranching enzyme (the glucanotransferase activity) 1' 4' 3' 2' Debranching enzyme (the α1,6 glucosidase activity) 2 Glucose...linked to protein 4' 3' 2' Glycogen phosphorylase 15 P 4 3- C 2...linked to protein 15 Glc-1-P...linked to protein 2- P 3 p. 40
27 The Powertrain of uman Metabolism (verview) CARBYDRATES PRTEIS LIPIDS Glucose Amino acids Fatty acids ther Carbohydrates xaloacetate 2 Glycogen Glucose-6-P Pyruvate Acetyl-CoA AD ATP Glycolysis C 2 2 Lactate Ketone bodies Ribose-5-P Cholesterol ADP AD p. 21
28 verall Goal: C C CARBYDRATES Glucose ther Carbohydrates Glycolysis PD 2 Glycogen Glucose-6-P Pyruvate Acetyl-CoA AD ATP C 2 C 2 2 Lactate (see p. 21)
29 Glucose 2AD ATP 2AD + + Cytosol Glycolysis 2x Pyruvate 2x Pyruvate 8AD + Mitochondria 2ATP 6x C 2 8AD + + Pyruvate Dehydrogenase (PD) Tricarboxylic Acid (TCA) Cycle
30
31
32 Inner-Membrane Transporters Are Powered by the Proton-Gradient + uter Membrane Pyr Intermembrane Space Inner Membrane + Pyr Mitochondrial Matrix
33 The Pyruvate Dehydrogenase (PD) Complex A. Additional Coenzymes Flavin Adenine Dinucleotide (FAD) Lipoic Acid (Lipoamide( Lipoamide) Coenzyme A (CoA( CoA-S)
34 FAD, FAD 2, FM, FM 2 2 Riboflavin (Vitamin B 2 ) 2 C C C C C 2 P P C 2 3 C C 3 C C 3 C 3 C C FAD 2 or FM 2 p. 41
35 Lipoic Acid (Lipoamide( Lipoamide) S S S S 2 C C (C 2 ) 4 C (C 2 ) 4 C 2 C C Rest C 2 C C 2 Lysine residue of enzyme (isopeptide bond) p. 42
36 Coenzyme A (CoA( CoA-S) Coenzyme A (CoA-S) 2 Pantothenic Acid (Vitamin B 5 ) C 2 P S C 2 C 2 C C 2 C 2 C C C 3 C C 2 P C 3 P CoA-S 3 C C S CoA Acetyl CoA p. 42
37 B. Reactions of the Pyruvate Dehydrogenase Complex verall Reaction Pyruvate + AD + + CoA-S Acetyl-CoA + C 2 + AD + + (ΔG o = kj mol -1 ) TPP FAD Five Co-factors: E1 E3 S S AD + Coenzyme A E2 TPP Lipoic Acid FAD cwx.prenhall.com p. 43
38 p. 43
39 C. Mechanism of Pyruvate Dehydrogenase (E1) R 1 "Business end" of TPP is thioazolium ring C 3 C C C S R2 R 1 C 3 C C C S Carbanion R2 - C C C 3 R 1 3 C C 3 C C C S R2 C 2 R 1 3 C Intermediates common to both PDC and PD enzymes C 3 C C R 2 C S C - p. 44
40 R 1 3 C C 3 C C R 2 C S C 2 R 1 3 C Intermediates common to both PDC and PD enzymes C 3 C C R 2 C S C - S S (C 2 ) 4 Lipoamide C Enzyme (E2) C 3 C 3 C C R2 R 1 + C S C S S (C 2 ) 4 C Enzyme (E2) CoenzymeA (CoA or CoAS) 3 C C ScoA + S S (C 2 ) 4 E2 FAD 2 C FAD AD + Acetyl-CoA AD + + p. 44
41 Glucose 2AD + Cytosol 2 2 2ATP 2AD + + Glycolysis 2 Pyruvate 2 Pyruvate 2AD + 2CoA-S Mitochondria 2C 2 2AD + + PD Complex 2 Acetyl~CoA
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