1. Metabolism:

2. Key words Metabolism – definition
Catabolism and anabolism – definition, example
Identify/distinguish structure of coenzymes
Identify structure of ATP

3. What is Metabolism?
The study of the biochemical reactions in an organism, including the coordination, regulation and energy needs
Definition: Metabolism is the sum total of the chemical reactions of biomolecules in an organism
Metabolism consists of
catabolism: the breakdown of larger molecules into smaller ones; an oxidative process that releases energy
anabolism: the synthesis of larger molecules from smaller ones; a reductive process that requires energy
Catabolism: the oxidative breakdown of nutrients
Anabolism: the reductive synthesis of biomolecules

4. Terminology in Metabolism
Metabolic pathway: A sequence of reactions, where the product of one reaction becomes the substrate for the next reaction.
- either linear pathway or cyclic pathway
- metabolic pathways proceed in many stages, allowing for efficient use of energy
Metabolites: intermediates in metabolic pathway
light
Eg CO2(g) + 6 H2O(l) → C6H12O6(aq) + 6 O2(g)
Anabolism
photosynthesis
C6H12O6 (aq) + 6O2 (g) → 6CO2 (g) + 6H2O
Catabolism
respiration

5. Metabolic pathway

6. Metabolic pathway: linear or cyclic

7. A Comparison of Catabolism and Anabolism
• Metabolism is the sum total of the chemical reactions of biomolecules in an organism

8. Metabolism Metabolism involves the energy flow in the cell
Photoautotroph via photosynthesis transfers the energy to heterotrophs
Heterotrophs obtain the energy through oxidation/reduction of organic compounds (carbohydrate, lipid and proteins)
 Food supplies the energy
Energy = ATP

9. The Role of Oxidation and Reduction in Metabolism
Oxidation-Reduction (redox) reactions are those in which electrons are transferred from a donor to an acceptor
oxidation: the loss of electrons; the substance that loses the electrons is called a reducing agent
reduction: the gain of electrons; the substance that gains the electrons is called an oxidizing agent
Carbon in most reduced form- alkane
Carbon in most oxidized form- CO2 (final product of catabolism)
Reduced Oxidized

10. Oxidation and Reduction in Metabolism
Reduction – gain e
Oxidation – less e
Oxidizing agent – e acceptor
reducing agent – e donor

11. Metabolism: Features Metabolic pathway: Enzymes – multienzymes
A group of noncovalently associated enzymes that catalyze 2 or more sequential steps in metabolic/biochemical pathway
Metabolic pathway:
Enzymes – multienzymes
Coenzymes
ATP – produced or used
Regulation of metabolic pathway:
Feedback inhibition or
Feed-forward activation

12. Metabolism: Regulation
Regulation of metabolic pathway:
Feedback inhibition = product (usually ultimate product) of a pathway controls the rate of synthesis through inhibition of an early step (usually the first step)
A  B  C  D  E  P
Feed-forward activation = metabolite produced early in pathway activates enzyme that catalyzes a reaction further down the pathway E1 E2 E3 E4 E5 — E1 E2 E3 E4 E5 +

13. Coenzymes Coenzymes in metabolism: NAD+/NADH NADP+/NADPH FAD+/FADH2
Coenzyme A (CoASH) – activation of metabolites
Electron carriers

14. NAD+/NADH: An Important Coenzyme
Nicotinamide adenine dinucleotide (NAD+) is an important coenzyme
Acts as a biological oxidizing agent
The structure of NAD+/NADH is comprised of a nicotinamide portion.
It is a derivative of nicotinic acid
NAD+ is a two-electron oxidizing agent, and is reduced to NADH
Reduced form, NADH carries 2 electrons

15. NADP+/NADPH: Also comprised of nicotinamide portion
Nicotinamide adenine dinucleotide phosphate (NADP+) – oxidizing agent
NADPH involves in reductive biosynthesis
Differ with NAD+ at ribose (C2 contain a phosphoryl group, PO32-
As electron carrier in photosythesis and pentose phosphate pathway
Reduced form, NADPH carries 2 electrons
Anabolism

16. The Structures Flavin Adenine Dinucleotide (FAD)
FAD is also a biological oxidizing agent
FAD – can accept one-electron or two-electron
The terminal e acceptor (O2) can accept only unpaired e (e must be transferred to O2 one at a time)
FADH carries 1 electron, FADH2 carries 2 electrons

17. FAD/FADH2 * FADH (semiquinone form) carries 1 electron,
FADH2 (fully reduced hydroquinone form) carries 2 electrons * 1 1
Formation of fully reduced hydroquinone form bypass the semiquinone form

18. Coenzyme A in Activation of Metabolic Pathways
A step frequently encountered in metabolism is activation
activation: the formation of a more reactive substance
A metabolite is bonded to some other molecule and the free-energy change for breaking the new bond is negative.
Causes next reaction to be exergonic

19. Coenzyme A (CoASH)
Coenzyme A – functions as a carrier of acetyl and other acyl groups
Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA: is a “high-energy” compound because of the presence of thioester bond – hydrolysis will release energy

20. ATP- high energy compound
ATP is essential high energy bond-containing compound
Phosphorylation of ADP to ATP requires energy
Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation: the addition of phosphoryl (PO32-) group/Pi (inorganic phosphate)

21. Metabolism:
(2)

22. ATP- high energy compound
ATP is essential high energy bond-containing compound
Phosphorylation of ADP to ATP requires energy
Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation: the addition of phosphoryl (PO32-) group/Pi (inorganic phosphate)

23. The Phosphoric Anhydride Bonds in ATP are “High Energy” Bonds
bonds that require or release convenient amounts of energy, depending on the direction of the reaction
Couple reactions: the energy released by one reaction, such as ATP hydrolysis, provides energy for another reactions to completion – in metabolic pathway
Phosphoanhydride /

24. Couple reaction: example

25. Role of ATP as Energy Currency
Phosphorylation of ADP requires energy from breakdown of nutrients (catabolism)
The energy from hydrolysis of ATP will be used in the formation of products (anabolism)

26. Metabolism of Carbohydrate
Catabolism
Anabolism

27. Major pathways of carbohydrate metabolism.
Fig 8.1 3rd ed

28. Key words Glycolysis, the fate for pyruvate
Substrate-level phosphorylation and oxidative phosphorylation

29. Glycolysis Glycolysis is the first stage of glucose metabolism
Glycolysis converts 1 molecule of glucose to 2 units of pyruvate (three C units) and the process involves the synthesis of ATP and reduction of NAD+ (to NADH)
The pathway has 10 steps/reactions
Glycolysis are divided into 2 stages/phases,
Phase 1=1st 5 reactions
Phase 2=2nd 5 reactions
Linear pathway

30. Glycolysis has a net “profit” of 2 ATP per glucose
Glycolysis are divided into 2 stages/phases,
Phase 1=1st 5 reactions
Energy investment –
A hexose sugar (glucose) is split into
2 molecules of three-C metabolite (glyceraldehyde-3-phosphate = GAP). The process consume 2 ATP
Phase 2=2nd 5 reactions
Energy recovery –
The two molecules of GAP are converted to 2 molecules of pyruvate with the generation of 4 ATP and 2 NADH.
Overall equation –
Glucose + 2 NAD+ + 2 ADP + 2Pi 
2 pyruvate + 2 NADH + 2 ATP + 2 H2O + 4H+
Glycolysis has a net “profit” of 2 ATP per glucose

31. The Reactions of Glycolysis
glucokinase 1
Phosphorylation of glucose to give glucose-6-phosphate
Isomerization of glucose-6-phosphate to give fructose-6-phosphate
Phosphorylation of fructose-6-phosphate to yield fructose-1,6-bisphosphate
Cleavage of fructose-1,6,-bisphosphate to give glyceraldehyde-3-phosphate and dihydroxyacetone phosphate
Isomerization of dihydroxyacetone phosphate to give glyceraldehyde-3-phosphate – isomerase enzyme
Use ATP 2
Use ATP 3
phosphofructokinase 4 5

32. The Reactions of Glycolysis (Cont’d)
Glyceraldehyde-3-P dehydrogenase
Oxidation of glyceraldehyde-3-phosphate to give 1,3-bisphosphoglycerate
Transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP to give 3-phosphoglycerate
Isomerization of 3-phosphoglycerate to give 2-phosphoglycerate
Dehydration of 2-phosphoglycerate to give phosphoenolpyruvate
Transfer of a phosphate group from phosphoenolpyruvate to ADP to give pyruvate
oxidation 6
Electron acceptor – NAD+
transfer 7
Phosphorylation of ADP to ATP 8
isomerization
dehydration 9
transfer 10
Phosphorylation of ADP to ATP

33. By kinase enzyme at step 1, 3, 7 and 10
Glycolysis
Dephosphorylation of ATP
Phosphorylation of ADP
Oxidation of intermediates and reduction of NAD+ to NADH by dehydrogenase reactions
- step 6
- glyceraldehyde-3-phosphate dehydrogenase
By kinase enzyme at step 1, 3, 7 and 10

34. ATP production
ATP is produced by phosphorylation of ADP - is through substrate-level phosphorylation
Substrate-level phosphorylation – the process of forming ATP by phosphoryl group transfer from reactive intermediates to ADP
1,3-bisphosphoglycerate and phosphoenolpyruvate – “high-energy” intermediates/compounds
Oxidative phosphorylation – the process of forming ATP via the pH gradient as a result of the electron transport chain.
Glycolysis - Step 7 and 10

35. Fates of Pyruvate From Glycolysis
Once pyruvate is formed, it has one of several fates
In aerobic metabolism- pyruvate will enter the citric acid cycle, end product in aerobic metabolism CO2 and H2O
In anaerobic metabolism- the pyruvate loses CO2
produce ethanol = alcoholic fermentation
produce lactate = anaerobic glycolysis

36. Anaerobic Metabolism of Pyruvate
Under anaerobic conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate
Lactate dehydrogenase (LDH) is a tetrameric isoenzyme consisting of H and M subunits; H4 predominates in heart muscle, and M4 in skeletal muscle
In muscle, during vigorous exercise – demand of ATP  but O2 is in short supply  is largely synthesized via anaerobic glycolysis which rapidly generates ATP rather than through slower oxidative phosphorylation

37. Alcoholic Fermentation
In anaerobic bacteria
Two reactions lead to the production of ethanol:
Decarboxylation of pyruvate to acetaldehyde
Reduction of acetaldehyde to ethanol
• Pyruvate decarboxylase is the enzyme that catalyzes the first reaction
This enzyme require Mg2+ and the cofactor, thiamine pyrophosphate (TPP)
• Alcohol dehydrogenase catalyzes the conversion of acetaldehyde to ethanol

38. NAD+ Needs to be Recycled to Prevent Decrease in Oxidation Reactions

39. Structure of cell
Cytoplasm/
Cytosol

41. Where does the Glycolysis Take Place?
Cytosol
Glycolysis is universal!

42. = Krebs Cycle, Tricarboxylic acid Cycle (TCA)
Citric Acid Cycle
= Krebs Cycle, Tricarboxylic acid Cycle (TCA)

43. Metabolism: Features Metabolic pathway: Enzymes – multienzymes
A group of noncovalently associated enzymes that catalyze 2 or more sequential steps in metabolic/biochemical pathway
Metabolic pathway:
Enzymes – multienzymes
Coenzymes
ATP – produced or used

44. Couple reaction: example

45. Coenzymes Coenzymes in metabolism: NAD+/NADH NADP+/NADPH FAD+/FADH2
Coenzyme A (CoASH) – activation of metabolites
Electron carriers

46. Glycolysis has a net “profit” of 2 ATP per glucose
Glycolysis are divided into 2 stages/phases,
Phase 1=1st 5 reactions
Energy investment –
A hexose sugar (glucose) is split into
2 molecules of three-C metabolite (glyceraldehyde-3-phosphate = GAP). The process consume 2 ATP
Phase 2=2nd 5 reactions
Energy recovery –
The two molecules of GAP are converted to 2 molecules of pyruvate with the generation of 4 ATP and 2 NADH.
Overall equation –
Glucose + 2 NAD+ + 2 ADP + 2Pi 
2 pyruvate + 2 NADH + 2 ATP + 2 H2O + 4H+
Glycolysis has a net “profit” of 2 ATP per glucose

47. Fates of Pyruvate From Glycolysis
Once pyruvate is formed, it has one of several fates
In aerobic metabolism- pyruvate will enter the citric acid cycle, end product in aerobic metabolism CO2 and H2O
In anaerobic metabolism- the pyruvate loses CO2
produce ethanol = alcoholic fermentation
produce lactate = anaerobic glycolysis
Glycolysis – in cytoplasm

48. Key words Definition – citric acid cycle Explain the citric acid cycle
Distinguish between glycolysis and citric acid cycle
Understand -oxidation – catabolism of lipid

49. Citric acid cycle Requires aerobic condition
Amphibolic (both catabolic & anabolic)
Serves 2 purposes:
Oxidize Acetyl-CoA to CO2 to produce energy (ATP & reducing power of NADH & FADH2)-involved in the aerobic catabolism of carbohydrates, lipids and amino acids
Supply precursors for biosynthesis of carbohydrates, lipids, amino acids, nucleotides and porphyrins

50. = Tricarboxylic acid Cycle
Citric Acid Cycle
= Krebs Cycle
= Tricarboxylic acid Cycle
(TCA)

51. TCA
Circular pathway
Two-carbon unit needed at the start of the citric acid cycle
The two-carbon unit is acetyl-CoA
Involves 8 reactions
The overall reaction from 1 acetyl-CoA produce 3 NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1 ATP)

52. Pyruvate is converted to Acetyl-CoA – activation of pyruvate
Pyruvate dehydrogenase complex is responsible for the conversion of pyruvate to acetyl-CoA
Five enzymes in complex
Requires the presence of cofactors TPP (thymine pyrophosphate), FAD, NAD+, and lipoic acid and coenzyme A (CoA-SH)
The overall reaction of the pyruvate dehydrogenase complex is the conversion of pyruvate, NAD+, and CoA-SH to acetyl-CoA, NADH + H+, and CO2
Oxidation of pyruvate and reduction of NAD+ 3C
Pyruvate = pyruvic acid 2C
Thioester, high energy compound

53. Coenzyme A (CoASH)
Coenzyme A – functions as a carrier of acetyl and other acyl groups
Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA: is a “high-energy” compound because of the presence of thioester bond – hydrolysis will release energy

54. Features of TCA Circular pathway
Mitochondrial matrix
Electron acceptor – NAD+ and FAD
Circular pathway
Two-carbon unit needed at the start of the citric acid cycle
The two-carbon unit is acetyl-CoA
Involves 8 reactions
The overall reaction from 1 acetyl-CoA produce 3 NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1 ATP)
X 2
How about 1 molecule of glucose?

55. Citric acid cycle - features
Oxidation decarboxylation
- CO2 leaves at step 3 and 4
Oxidation of intermediates and reduction of NAD+ to NADH by dehydrogenase reactions
- step 3, 4 and 8
- isocitrate dehydrogenase
- α-ketoglutarate dehydrogenase
- malate dehydrogenase
Oxidation of intermediates and reduction of FAD+ to FADH2 by succinate dehydrogenase reaction
- step 6
Phosphorylation of GDP to GTP – step 5

56. Where does the Citric Acid Cycle Take Place?
In eukaryotes, cycle takes place in the mitochondrial matrix
In prokaryotes?
Cytoplasm

57. The Central Relationship of the Citric Acid Cycle to Catabolism
TCA involves 8 series of reactions that oxidizes the acetyl group of acetyl-CoA to 2 molecules of CO2 and the energy is conserves in NADH, FADH2 and “high-energy” compound, GTP
Acetyl-CoA – synthesize from pyruvate (glycolysis product)
Guanosine – Tri-Phosphate

58. Aerobic catabolism
NADH, FADH2 from glycolysis and TCA will enter the Electron Transport Chain (ETC) to produce more ATP (oxidative phosphorylation)
1 NADH = 2.5 ATP,
1 FADH2 = 1.5 ATP
ETC take place in mitochondria - inner membrane (eukaryotes)
In ETC
In prokaryotes?
Plasma membrane

59. Oxidation of Pyruvate Forms CO2 and ATP
Aerobic metabolism is more efficient than anaerobic metabolism

60. Citric acid cycle - amphibolic
Amphibolic (both catabolic & anabolic)
Serves 2 purposes:
Oxidize Acetyl-CoA to CO2 to produce energy (ATP & reducing power of NADH & FADH2)-involved in the aerobic catabolism of carbohydrates, lipids and amino acids
Supply precursors for biosynthesis (anabolism) of carbohydrates, lipids, amino acids, nucleotides and porphyrins
Replenish TCA- catabolism of amino a. and fatty a.
Anabolic pathway
Require aerobic condition

61. Differences between glycolysis & TCA cycle
Glycolysis is a linear pathway; TCA cycle is cyclic
Glycolysis occurs in the cytosol and TCA is in the mitochondrial matrix
Glycolysis does / does not require oxygen; TCA requires oxygen (aerobic)

62. Lipids are Involved in Generation and Storage of Energy
The oxidation of fatty acids (FA)in triacylglycerols are the principal storage form of energy for most organisms
Their carbon chains are in a highly reduced form
The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

63. Catabolism of Lipids - triacylglycerol
Lipases catalyze hydrolysis of bonds between fatty acid and the rest of triacylglycerols
Phospholipases catalyze hydrolysis of bonds between fatty acid and the rest of phosphoacylglycerols
May have multiple sites of action

64. Catabolism of fatty acid - -Oxidation
-Oxidation: a series of reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid
The complete cycle of one -oxidation requires four enzymes/steps
Take place in mitochondria matrix
Spiral pathway
1 round of -oxidation = yield 1 NADH, 1 FADH2 and 1 acetyl-CoA

65. METABOLISM
REVISION

66. Catabolism: the oxidative breakdown of nutrients
Anabolism: the reductive synthesis of biomolecules
Catabolism – features
Release energy (ADP ATP)
Oxidizing agent (NAD+, FAD)
Anabolism – features
Use energy (ATP  ADP)
Reducing agent (NADH ,FADH2)
Metabolism – the sum total of biochemical reaction carried out by organism

67. Metabolism Metabolism involves the energy flow in the cell
Photoautotroph via photosynthesis transfers the energy to heterotrophs
Heterotrophs obtain the energy through oxidation/reduction of organic compounds (carbohydrate, lipid and proteins)
 Food supplies the energy
Energy = ATP

68. Major pathways of carbohydrate metabolism.
Fig 8.1 3rd ed

69. Glycolysis Linear pathway
Glycolysis is the first stage of glucose metabolism
Glycolysis converts 1 molecule of glucose to 2 units of pyruvate (three C units) and the process involves the synthesis of ATP and reduction of NAD+ (to NADH)
The pathway has 10 steps/reactions
Glycolysis are divided into 2 stages/phases,
Phase 1=1st 5 reactions
Phase 2=2nd 5 reactions

70. Fates of Pyruvate From Glycolysis
Once pyruvate is formed, it has one of several fates
In aerobic metabolism- pyruvate will enter the citric acid cycle, end product in aerobic metabolism CO2 and H2O
In anaerobic metabolism- the pyruvate loses CO2
produce ethanol = alcoholic fermentation
produce lactate = anaerobic glycolysis
Glycolysis – in cytoplasm

71. ATP – energy carrier / an energy transfer agent
ATP- high energy compound
ATP – energy carrier / an energy transfer agent
ATP is essential high energy bond-containing compound
Phosphorylation of ADP to ATP requires energy
Hydrolysis of ATP to ADP releases energy
nucleotide
Phosphorylation: the addition of phosphoryl (PO32-) group/Pi (inorganic phosphate)

72. Coenzyme A (CoASH)
Coenzyme A – functions as a carrier of acetyl and other acyl groups
Has sulfhydryl/thiol group
Thioester bond
CoASH
Acetyl-CoA: is a “high-energy” compound because of the presence of thioester bond – hydrolysis will release energy

73. TCA
Circular pathway
Two-carbon unit needed at the start of the citric acid cycle
The two-carbon unit is acetyl-CoA
Involves 8 reactions
The overall reaction from 1 acetyl-CoA produce 3 NADH, 1 FADH2, 2 CO2 and 1 GTP (equivalent to 1 ATP)

74. Citric acid cycle - amphibolic
Amphibolic (both catabolic & anabolic)
Serves 2 purposes:
Oxidize Acetyl-CoA to CO2 to produce energy (ATP & reducing power of NADH & FADH2)-involved in the aerobic catabolism of carbohydrates, lipids and amino acids
Supply precursors for biosynthesis (anabolism) of carbohydrates, lipids, amino acids, nucleotides and porphyrins
Replenish TCA- catabolism of amino a. and fatty a.
Anabolic pathway
Require aerobic condition

75. Where does the Citric Acid Cycle Take Place?
In eukaryotes, cycle takes place in the mitochondrial matrix
In prokaryotes?
Cytoplasm