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BCM208 Metabolic Biochemistry

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Presentation on theme: "BCM208 Metabolic Biochemistry"— Presentation transcript:

1 BCM208 Metabolic Biochemistry
Topic 2: Carbohydrate Metabolism 1

2 Objectives Understand the importance of glucose catabolism
Define the terms: Glycolysis Fermentation Transcribe the complete glycolysis pathway leading from glucose to pyruvate, including: The names of all intermediates The names of all enzymes The names of cofactors Indicate which of the reactions of the glycolytic pathway are reversible and which are not Indicate which of the reactions form ATP and which require ATP Describe the fate of pyruvate in anaerobic fermentations State the stoichiometry of the glycolytic pathway, in relation to both ATP production and electron balance Understand the Pasteur effect Appreciate the metabolic function of the pentose phosphate pathway Describe the metabolic function of the pentose phosphate pathway leading to ribose-5-phosphate Transcribe the chemical reactions of steps in the gluconeogenesis pathway which are not the reverse of reactions of the glycolysis pathway

3 Importance of glucose catabolism
Glucose is the major fuel of most organisms Storage as high mw polymer allows high energy storage with low cytosolic osmolarity Glucose is a precursor of many compounds 2

4 3 major fates of Glucose 1. Stored as sucrose or polysaccharide
2. Oxidized to pyruvate via glycolysis or 3. Oxidized to pentoses via the pentose phosphate pathway

5 Fates of Glucose Fig

6 Catabolic fate of Pyruvate
Fig. 15-3

7 Glycolysis A molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of pyruvate Students are expected to be able to write out the compete glycolytic pathway from glucose to pyruvate (Structures not required)

8 Important points to note
Which enzymes are reversible and which are rate limiting Which steps use/form ATP What coenzymes are involved and where

9 2 Phases of glycolysis Preparatory phase Payoff phase

10 Preparatory phase of glycolysis
1 mole of glucose converted into 2 moles of glyceraldehyde-3-phosphate 2 moles of ATP utilized 5 enzymes steps are involved

11 Preparatory phase of glycolysis (cont.)
Fig 15 -2a

12 1. Phosphorylation of glucose

13 2. Conversion of Glucose 6-phosphate to fructose 6-phosphate

14 3. Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate

15 4. Cleavage of fructose 1,6-bisphosphate

16 5. Interconversion of the triose phosphates

17 Enzymes of glycolysis - Preparatory phase
1. Hexokinase: irreversible, ATP is consumed, requires Mg2+ 2. Phosphohexose isomerase: requires Mg2+ 3. Phosphofrutokinase: irreversible, slow, rate limiting, point of regulation, ATP is consumed, requires Mg2+ 4. Fructose-1,6-bisphosphate aldolase 5. Triose phosphate isomerase

18 Payoff phase of glycolysis
2 moles of pyruvate formed from 2 moles of glyceraldehyde-3-phosphate The first step is the only oxidation reaction, NAD+ is reduced to NADH 4 moles of ATP are formed 5 enzymes steps are involved

19 Payoff phase of glycolysis (cont.)
Fig 15 -2b

20 6. Oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate

21 7. Phosphoryl transfer from 1,3-bisphophoglycerate to ADP

22 8. Conversion of 3-phophoglycerate to 2-phosphoglycerate

23 9. Dehydration of 2-phopoglycerate to phophoenolpyruvate

24 10. Transfer of phosphoryl group from phosphoenolpyruvate to ADP

25 Enzymes of glycolysis - Payoff Phase
1. Glyceraldehyde-3-phosphate dehydrogenase: NAD+ is the co-factor. 2. Phosphoglycerate kinase: ATP is formed, requires Mg2+ 3. Phosphoglycerate mutase: requires Mg2+ 4. Enolase: this enzyme can be inhibited by fluoride 5. Pyruvate kinase: an irreversible enzyme, point of regulation, ATP is formed. requires Mg2+ and K+

26 Overall balance Glucose + 2ATP + 2NAD+ + 4ADP + 2Pi --> 2 pyruvate + 2ADP + 2 NADH + 2H+ + 4ATP + 2H20 or Glucose + 2NAD+ +2ADP + 2 Pi --> 2 pyruvate + 2NADH + 2H+ + 2ATP +2H20

27 The Pasteur effect When yeast are exposed to air the rate of glucose consumption drops dramatically Respiration is much more efficient than fermentation Result of cells adenylate energy charge

28 Energy Charge Energy charge = [ATP]+1/2[ADP] ---------------------
[ATP]+[ADP]+[AMP] High energy charge -> adequate ATP Low energy charge -> ATP deficiency Glycolysis inhibited by ATP activated by ADP and AMP

29 Alcohol Fermentation Fermentation of glucose to ethanol and carbon dioxide by the yeast, eg. Saccharomyces cerevisiae

30 Steps in Alcoholic Fermentation
Glucose converted to pyruvate by glycolysis Pyruvate decarboxylated to acetaldehyde by pyruvate decarboxylase (cofactors: TPP, Mg2+) Acetaldehyde reduced to ethanol by alcohol dehydrogenase

31 Steps in Alcoholic Fermentation (cont.)

32 Alcohol dehydrogenase
Also removes ethanol from the blood In reduced amounts in some races

33 Thiamine Pyrophosphate (TPP)
A coenzyme derived from vitamin B1 Vit B1 deficiency causes beri beri (accumulation of body fluids) TPP plays an important role in cleavage of bonds adjacent to a carbonyl group and in chemical rearrangements involving transfer of an activated aldehyde group

34 Lactate Fermentation Under anaerobic conditions in muscle tissue pyruvate may be converted to lactate by the enzyme lactate dehydrogenase to regenerate NAD+ from NADH Some microorganisms ferment glucose and other hexoses to lactate. This is important in the food industry, eg, some lactobacilli and streptococci ferment lactose in milk to lactic acid. The dissociation of lactate and H+ lowers the pH which denatures the milk proteins to form yogurt .

35 Lactate fermentation (con.t)

36 3 Types of lactate Fermentation
Homofermentative pathway: 1 mol of glucose produces 2 mols of lactate (eg Lactobaccillus bulgaricus in yogurt production) Heterofermentative pathway: 1 mol of glucose produces 1 mol of lactate, 1 mol of ethanol and 1 mol of carbon dioxide (eg Leuconostoc mesenteroides in sauerkraut production) Bifidium Pathway: produces acetate and lactate in the ratio of 3:2 per 2 mols of glucose (eg Bifidobacterium bifidium in breast-fed babies intestinal flora)

37 Malo-lactate fermentation
A fermentation which can occur in wine Carried out by some lactic acid bacteria in the presence of a fermentable sugar and malate: Oenococcus oeni (Leucostoc oenos) Malate is converted to lactate and carbon dioxide

38 Feeder pathways for glycolysis
Glycogen/Starch Monosaccharides and disaccharides

39 Starch and glycogen degradation
Starch and Glycogen consist of 1,4 (straight chains) and 1,6 (branch)-glycosidic bonds Broken down to glucose by phosphorlysis in cells Broken down by hydrolysis in the intestinal tract Glycogen phosphorylase: splits glucose-1-phosphate from the non-reducing ends Debranching enzyme: removes branches

40 Glycogen degradation Fig

41 Feeding mono- and disaccharides to Glycolytic pathway
Disaccharides split into monosaccharides Monosaccharides enter glycolysis after conversion to a phosphorylated derivative Fructose has 2 alternative routes: via fructose-1-phosphate (in liver) via fructose-1-phosphate (spermatozoa)

42 Carbohydrate entry into glycolysis
Fig

43 Regulation of carbohydrate catabolism
Pathways can be regulated by rate-limiting and non-reversible steps Hexokinase is inhibited by its product Pyruvate kinase inhibited by ATP by decreasing affinity for its substrate inhibited by acetyl-CoA and long chain fatty acids (fuel for citric acid cycle)

44 Regulation of carbohydrate catabolism (cont.)
Phosphofructokinase 1 inhibited by ATP by lowering affinity ADP and AMP activate Citrate increases effect of ATP Fructose-2,6-bisphosphate activates PFK-1 and is under hormonal control Fructose-2,6-bisphosphate inhibits the reverse reaction in gluconeogenesis

45 Pentose phosphate pathway
Alternative glucose catabolism with 2 purposes: synthesis of NADPH synthesis to ribose-5-phosphate The oxidative phase should be learnt

46 Pentose phosphate pathway (cont.)
Most active in: dividing cells (require ribose for nucleic acid) adipose tissue (NADPH for fatty acid biosynthesis) red blood cells (NADPH to prevent haemoglobin from oxidative damage)

47 Oxidative reactions of the pentose phosphate pathway
Fig

48 Carbohydrate Biosynthesis
Fig

49 Gluconeogenesis Formation of glucose from non-hexose precursors
Glucose is required in mammals as it is the sole source of energy for some tissues Gluconeogenesis is found in animals, plants, fungi and microorganisms (eg bacteria can survive on substrates such as lactate which they can convert to glucose) The reverse process of glycolysis

50 Irreversible enzymes of glycolysis
Hexokinase: Glu --> Glu-6-P Phosphofructokinase-1 Fru-6-P --> Fru-1,6-P Pyruvate kinase Phosphoenolpyruvate --> pyruvate

51 Free Energy changes in glycolytic pathway

52 Gluconeogenesis bypass steps
Fig

53 Pyruvate --> Phosphoenolpyruvate bypass
Fig 20 -3

54 Alternative path from pyruvate to PEP
Fig 20-4

55 Fru-1,6-P --> Fru-6-P bypass
Catalysed by a different enzyme: Fructose-1,6-bisphosphatase Mg2+ dependent Fructose-1,6-bisphosphate + H2O --> fructose-6-phosphate + Pi

56 Glu-6-P --> Glucose bypass
Dephosphorylation of glu-6-P Enzyme: glucose-6-phosphatase Mg2+ dependent Glu-6-phosphate + H2O --> glucose + Pi

57 Gluconeogenesis is energetically costly
Sum of reactions: 2pyruvate + 4ATP + 2GTP + 2NADH + 4H2O --> glucose + 4ADP + 2GDP + 6Pi + 2NAD+ + 2H+

58 Gluconeogenesis summary
Table 20-2

59 Gluconeogenesis regulation
Regulated by acetyl CoA Acetyl CoA stimulates the activity of pyruvate carboxylase and inhibits the pyruvate dehydrogenase complex

60 Gluconeogenesis regulation (cont.)
Fructose-1,6-bisphosphatase inhibited by AMP Corresponding glycolytic enzyme (phosphofructokinase-1) is stimulated by AMP and ADP but inhibited by citrate and ATP Fructose-2,6-bisphosphate (hormone controlled, allosteric effector) stimulates phosphofructokinase-1 and inhibits Fructose-1,6-bisphosphatase

61 Postharvest ripening bananas
Starch is the dominant carbohydrate in bananas when harvested It is during transport and storage that the starch is broken down to simple sugars

62 Postharvest ripening bananas (cont.)
This process is catalysed by phosphorylase activity: fig 15-12

63 Postharvest ripening bananas (cont.)
The consequence of this process is that bananas can be safely transported and stored, as starch is more resistant to breakdown from microorganisms

64 Respiration/Fermenation summary

65 Glycolysis summary Preparatory phase

66 Glycolysis summary (cont.)
Payoff phase

67 16


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