1. Introduction to Metabolism
Chapter 9
Introduction to Metabolism
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. An Overview of Metabolism
metabolism is the total of all chemical reactions in the cell and is divided into two parts
catabolism – energy-conserving reactions that also generate a ready supply of electrons (reducing power) and precursors for biosynthesis
anabolism – the synthesis of complex organic molecules from simpler ones
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

3. Anabolism requires energy
transferred from energy source to the synthetic systems of the cell in the form of ATP
also requires a source of electrons stored in the form of reducing power
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

4. Energy and Work
energy
capacity to do work or to cause particular changes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

5. Types of work carried out by organisms
chemical work
synthesis of complex molecules
transport work
take up of nutrients, elimination of wastes, and maintenance of ion balances
mechanical work
cell motility and movement of structures within cells
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

6. The Laws of Thermodynamics
a science that analyzes energy changes in a collection of matter called a system (e.g., a cell)
all other matter in the universe is called the surroundings
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

7. Energy units calorie (cal) joules (J)
amount of heat energy needed to raise 1 gram of water from 14.5 to 15.5°C
joules (J)
units of work capable of being done by a unit of energy
1 cal of heat is equivalent to J of work
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

8. First law of thermodynamics
energy can be neither created nor destroyed
total energy in universe remains constant
however energy may be redistributed either within a system or between the system and its surroundings
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

9. Second law of thermodynamics
entropy
amount of randomness or disorder in a system
physical and chemical processes proceed in such a way that the randomness or disorder of the universe increases to the maximum possible
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

10. Free Energy and Reactions
G = H - T• S
expresses the change in energy that can occur in chemical reactions and other processes
used to indicate if a reaction will proceed spontaneously
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

11. G = H - T• S G H T S free energy change
amount of energy that is available to do work H
change in enthalpy (heat content) T
temperature in Kelvin S
change in entropy occurring during the reaction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

12. consider the chemical reaction
Chemical equilibrium
equilibrium
consider the chemical reaction
A + B C + D
reaction is at equilibrium when rate of forward reaction = rate of reverse reaction
equilibrium constant (Keq)
expresses the equilibrium concentrations of products and reactants to one another
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

13. Standard free energy change (Go´)
free energy change defined at standard conditions of concentration, pressure, temperature, and pH
Go´
standard free energy change at pH 7
directly related to Keq
Go´ = RT•logKeq
R: gas constant
T: absolute temp.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

14. The Relationship… Figure 9.1 (reaction proceeds spontaneously)
(reaction will not proceed
Figure 9.1
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

15. Adenosine 5’-triphosphate (ATP) - Energy Currency of the Cell
Figure 9.2
a model of ATP
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

16. Role of ATP in metabolism
Figure 9.3
Exergonic breakdown of ATP is coupled with endergonic
reactions to make them more favorable
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

17. The Cell’s Energy Cycle
Figure 9.4
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

18. Oxidation-Reduction Reactions and Electron Carriers
many metabolic processes involve oxidation-reduction reactions (electron transfers)
electron carriers are often used to transfer electrons from an electron donor to an electron acceptor
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

19. Oxidation-Reduction (Redox) Reactions
can result in energy release, which can be conserved and used to form ATP
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

20. Standard Reduction Potential (E0)
equilibrium constant for an oxidation-reduction reaction (at pH7, E´0)
a measure of the tendency of the reducing agent to lose electrons
more negative E´0  better electron donor
more positive E´0  better electron acceptor
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

21. Copyright © The McGraw-Hill Companies, Inc
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

22. The greater the difference between the E´0 of the donor and
Acceptor 
the more
negative
the Go´
Go´ = -nF• E´0
Figure 9.5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

23. Electron Transport Chains
also known as electron transport system (ETS)
electron carriers organized into ETC with the first electron carrier having the most negative E´o
as a result the potential energy stored in first redox couple is released and used to form ATP
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

24. Electron Transport Systems
Mitochondria
Bacteria
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

25. Electron carriers NAD nicotinamide adenine dinucleotide NADP
nicotinamide adenine dinucleotide phosphate
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

26. Oxidation-reduction of NAD
NAD can accept electrons and a hydrogen from a reduced substrate (e.g. SH2). These are carried on the nicotinamide ring.
Oxidation-reduction of NAD
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

27. Model of NAD+
NAD can accept electrons and a hydrogen from a reduced substrate (e.g. SH2). These are carried on the nicotinamide ring.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

28. riboflavin FAD flavin adenine dinucleotide FMN flavin mononucleotide
a riboflavin phosphate
Riboflavin, a vitamin, is composed of the isoalloxazine ring and its attached circle (circled). Portion of the ring that is directly involved in oxidation-reactions is in color.
riboflavin
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

29. - also called ubiquinone * Menaquinone (VK2)
Coenzyme Q (CoQ)
- a quinone
- also called ubiquinone
* Menaquinone (VK2)
2H+ + 2e-
Mitochondria: UQ
Gram (+): MQ
Gram (-): UQ & MQ
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

30. - use iron to transfer electrons - iron is part of a heme group
Cytochromes
- use iron to transfer electrons
- iron is part of a heme group
- heme + proteins
Structure of heme a
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

31. A c-type cytochrome
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

32. nonheme iron proteins iron-sulfur proteins (e.g., ferredoxin)
contain iron-sulfur centers
use iron to transport electrons
iron is not part of a heme group but rather is associated with sulfur atoms
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

33. Enzymes protein catalysts catalyst substrates products
have great specificity for the reaction catalyzed and the molecules acted on
catalyst
substance that increases the rate of a reaction without being permanently altered
substrates
reacting molecules
products
substances formed by reaction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

34. Structure and classification of enzymes
some enzymes are composed solely of one or more polypeptides
some enzymes are composed of one or more polypeptides and nonprotein components
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

35. Enzyme structure apoenzyme cofactor holoenzyme = apoenzyme + cofactor
protein component of an enzyme
cofactor
nonprotein component of an enzyme
prosthetic group – firmly attached
coenzyme – loosely attached
holoenzyme = apoenzyme + cofactor
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

36. Coenzymes
often act as carriers, transporting substances around the cell
Figure 9.11
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

37. Table 9.2
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

38. The Mechanism of Enzyme Reactions
(e.g.) a typical exergonic reaction
A + B  AB‡  C + D
transition-state complex
(resembles both the substrates and the products)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

39. activation energy (Ea)
- energy required to form transition-state complex
enzyme speeds up reaction by lowering Ea
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

40. How enzymes lower Ea
by increasing concentrations of substrates at active site of enzyme
by orienting substrates properly with respect to each other in order to form the transition-state complex
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

41. Lock and Key Model of Enzyme Function
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

42. The Induced Fit Model of Enzyme Function
Yeast hexokinase and glucose
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

43. The Effect of Environment on Enzyme Activity
enzyme activity is significantly impacted by substrate concentration, pH, and temperature
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

44. Effect of [substrate] rate increases as [substrate] increases
no further increase occurs after all enzyme molecules are saturated with substrate
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

45. Effect of pH and temperature
each enzyme has specific pH and temperature optima
denaturation
loss of enzyme’s structure and activity when temperature and pH rise too much above optima
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

46. Enzyme inhibition • competitive inhibitor
- directly competes with binding of substrate to active site
• noncompetitive inhibitor
- binds enzyme at site other than active site; changes enzyme’s shape so that it becomes less active
Figure 8.19 – succinate dehydrogenase is inhibited by competitive inhibitor malonic acid
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

47. Competitive inhibition of enzyme activity
p-aminobenzoic acid: a substrate for folic acid biosynthesis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

48. The Nature and Significance of Metabolic Regulation
conservation of energy and materials
maintenance of metabolic balance despite changes in environment
three major mechanisms
metabolic channeling
: localize metabolites and enzymes into different parts of the cell (compartmentation)
stimulation or inhibition of enzyme activity (posttranslational regulation)
regulation of the amount of synthesis of a particular enzyme (posttranscriptional regulation)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

49. Metabolic Channeling
can generate marked variations
in metabolite concentrations
differential localization of enzymes and metabolites
compartmentation
differential distribution of enzymes and metabolites among separate cell structures or organelles
Figure 9.17
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

50. Control of Enzyme Activity
two important reversible control measures
allosteric regulation
noncovalent binding of allosteric effector changes activity of enzyme
covalent modification
covalent binding of a phosphoryl, methyl, or adenyl group changes activity of enzyme
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

51. Allosteric regulation
enzyme
enzyme inactive –
can’t bind substrate
effector
binding alters
shape of
active site
example of a positive effector
enzyme catalyzes
reaction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

52. Aspartate carbamoyltransferase regulation
ATP increases activity
CTP decreases activity
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

53. Covalent Modification of Enzymes - Regulation of Glutamine Synthetase Activity -
Figure 9.19
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

54. Feedback Inhibition also called end product inhibition
inhibition of one or more critical enzymes in a pathway regulates entire pathway
pacemaker enzyme
catalyzes the slowest or rate-limiting reaction in the pathway
ensures balanced production of a pathway end product
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

55. Feedback inhibition in a branching pathway
each end product regulates
the initial pacemaker iso(en)zymes
Iso(en)zymes : different
enzymes that catalyze same reaction
each end product
regulates its own branch of the pathway
Feedback inhibition of a branching pathway with two end products (P and Q). Reaction converting substrate A to intermediate B is catalyzed by isoenzymes, each regulated by a different end product (P or Q).
Figure 9.20
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

56. Chemotaxis
an example of a complex behavior that is regulated by altering enzyme activity
system involves a number of enzymes and other proteins that are regulated by covalent modification
a major component is a phosphorelay system consisting of a sensor kinase and response regulator
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

57. Proteins of the chemotaxis response in E. coli
Modulation of the activity of the phosphorelay system determines the rotational direction of the flagella and whether the cell will run or tumble
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

58. Signaling pathways of the chemotaxis response
Complexes of MCPs, CheW, and CheA in E. coli
MCP, CheA, and CheZ: homodimers / CheW, CheB, CheY, and CheR: monomers
Glutamic acid (4 - 6) in MCP: methylated
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

59. Methyl-accepting chemotaxis proteins of E. coli
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.