Pathway overview. Glucose + 2NAD + + 2ADP +2Pi 2NADH + 2pyruvate + 2ATP + 2H 2 O + 4H +

Size: px

Start display at page:

Download "Pathway overview. Glucose + 2NAD + + 2ADP +2Pi 2NADH + 2pyruvate + 2ATP + 2H 2 O + 4H +"

Allen Patterson
6 years ago
Views:

1 Glycolysis

2 Glycolysis The conversion of glucose to pyruvate to yield 2ATP molecules 10 enzymatic steps Chemical interconversion steps Mechanisms of enzyme conversion and intermediates Energetics of conversions Mechanisms controlling the Flux of metabolites through the pathway

4 Pathway overview Glucose + 2NAD + + 2ADP +2Pi 2NAD + 2pyruvate + 2ATP

6 exokinase C 2 Glucose Mg ++ C 2 P ATP + ADP + + Glucose-6-phosphate

7 Covalent modification-protein phosphorylation

8 Phosphoglucose Isomerase C 2 P PC 2 C 2

9 Phosphofructokinase -2 3 PC 2 C 2 Mg PC 2 C 2 P ATP + ADP Fructose-6-P 4 Fructose-1,6-bisphosphate

10 C 2 P 3-2 C Aldolase -2 C 2 P 3 C C Dihydroxyacetone phosphate (DAP) C C + C C 2 P 3-2 Fructose -1,6-bisphosphate (FBP) C C 2 P 3-2 Glyceraldehyde-3- phosphate (GAP) Aldol cleavage (retro aldol condensation)

11 Front half of glycolysis

12 Glyceraldehyde-3-phosphate dehydrogenase The first high-energy intermediate P 3 2- C + NAD + + Pi C + NAD C 2 P 3 2- C 2 P 3 2- Uses inorganic phosphate to create 1,3 bisphosphoglycerate

13 Phosphoglycerate Kinase: First ATP generation step P C + ADP C + ATP C 2 P 3 2- C 2 P 3 2-1,3 BPG 3 PG

14 Phosphoglycerate mutase - - C C P PG C 2 P 3 2- C - P 3-2 C 2 2PG C 2 P 3 2-2,3 BPG

15 Enolase generation of a second high energy intermediate - - C P 3-2 C P C 2 Phosphoglycerate Phosphoenol pyruvate

16 Pyruvate kinase: Second ATP generation step

17 The second half of glycolysis

18 The metabolic fate of pyruvate

19 The Citric acid cycle

20 The Citric acid cycle verall reaction 3NAD+ + FAD + GDP + Pi + acetyl-coa 3NAD + FAD + GTP + CoA + 2C 2

21 verview

22 The citric acid cycle enzymes are found in the matrix of the mitochondria Substrates have to flow across the outer and inner parts of the mitochondria

24 The five reactions of the pyruvate dehydrogenase multi enzyme complex

25 Citrate Synthase C 2 C + 3 C C SCoA C 2 C C 2

26 Induced fit needs binding of oxaloacetate before Acetyl CoA can bind. CoAS C C 3 Acetyl-CoA CoAS C C 2 Proposed intermediate CoAS C 2 C C 3 CoAS C 2 Acetonly CoA (ground-state analog) Carboxymethyl-CoA (transition state analog)

27 Aconitase C 2 C C 2 C 2 C C C 2 C C Citrate Cis-Aconitate Isocitrate The double bond is placed on the Pro-R arm

28 NAD + - Dependent Isocitrate dehydrogenase NAD + NAD

29 a-ketoglutarate dehydrogenase NAD + C 2 2 C C 2 C 2 C NAD C 2 CoAS

30 Succinyl-CoA Synthetase or succinate thiokinase

31 Succinate dehydrogenase C 2 C 2 C C + 2e The FAD on the enzyme itself is reduced

32 Succinate dehydrogenase is the only membrane bound enzyme in the citrate cycle Succ dh--fad 2 + Ubiquinone or Coenzyme Q 3 C 3 C C 3 C 3 C 2 n xidized form n = C C 3 3 C C 3 C 2 n Reduced form

33 Fumarase

34 Malate dehydrogenase 2 C NAD 2 C C C NAD +

35 Citric acid cycle intermediates are always in flux

36 Fig 19-2 Mitochondrion Double membrane, with inner membrane very impermeable TCA occurs in the matrix ETC in the inner membrane

37 Chemiosmotic Mechanism Electron transport chain sets up an + gradient (proton motive force). Energy of the pmf is harnessed to make ATP.

38 Electron transport chain

39 Gluconeogenesis

40 verview of Glucose Metabolism

41 Gluconeogenesis

42 Pyruvate is converted to oxaloacetate before being changed to Phosphoenolpyruvate

43 The Core Cycle

44 The glyoxylate pathway

45 Phosphopentose pathway 3G-6-P + 6NADP NADP C 2 + 2F6P + GAP

46 The pathway consists of three parts 1. xidative reactions: G-6-P + 6NADP NADP + 3C 2 + 3Ribulose-5-P 4 2. Isomerization and epimerization reactions: 3Ribulose-5-P 4 Ribose -5-P 4 + 2Xylulose-5-P 4 3. A series of C-C bond cleavage and formations: Ribose-5-P 4 + 2Xyluose-5-P 4 2F-6-P + GAP

48 Glucose-6 phosphate dehydrogenase

49 Phosphogluconate dehydrogenase

50 Ribulose-5-P 4 isomerase

52 Glycogen Storage Glycogen is a D-glucose polymer a(1 4) linkages a(1 6) linked branches every 8-14 residues

54 Glycogen Breakdown or Glycogenolysis Three steps Glycogen phosphorylase Glycogen + Pi <-> glycogen + G1P (n residues) (n-1 residues) Glycogen debranching Phosphofructomutase

55 Glycogen Phosphorylase Requires Pyridoxal-5 -phosphate PLP

56 Glycogen Debranching Enzyme

57 Phosphofructomutase

58 Glycogen Syntheisis

59 UDP-glucose Pyrophorylase

60 Glycogen Synthase

Respiration. Organisms can be classified based on how they obtain energy: Autotrophs

Respiration. Organisms can be classified based on how they obtain energy: Autotrophs Respiration rganisms can be classified based on how they obtain energy: Autotrophs Able to produce their own organic molecules through photosynthesis Heterotrophs Live on organic compounds produced by