BST 3022

Biochemistry II

1
What are the distinctive properties
of living systems?

Ÿ Functional structures

Ÿ Complicated and highly organized

Ÿ Energy transformation

Ÿ Self-replication
2
 BIOCHEMISTRY
• Structure and
Catalysis

Textbook:
Nelson, D. L. and Cox, M. M. (2021) 8th ed.
3
Biochemistry
Amino acids and proteins
Enzymes

Structure and Carbohydrates

Catalysis Lipids and biological membranes
Nucleotides and nucleic acids
Biochemical signaling

Carbohydrate metabolism
Citric acid cycle

Bioenergetics Oxidative phosphorylation

and Metabolism Photosynthesis
Metabolism of fatty acid and lipid
Metabolism of amino acid and nucleotide

4
 • Structural hierarchy in the molecular
organization of cells

Fig. 1-9

5
 BIOCHEMISTRY
• Structure and
Catalysis

• Bioenergetics and
Metabolism

Textbook:
Nelson, D. L. and Cox, M. M. (2021) 8th ed.
6
What are the distinctive properties
of living systems?

Ÿ Complicated and highly organized

Ÿ Functional structures

Ÿ Energy transformation

Ÿ Self-replication
7
Biochemistry
Amino acids and proteins
Enzymes

Structure and Carbohydrates

Catalysis Lipids and biological membranes
Nucleotides and nucleic acids
Biochemical signaling

Carbohydrate metabolism
Citric acid cycle

Bioenergetics Oxidative phosphorylation

and Metabolism Photosynthesis
Metabolism of fatty acid and lipid
Metabolism of amino acid and nucleotide

8
 BIOCHEMISTRY
• Structure and
Catalysis

• Bioenergetics and
Metabolism

• Information
Pathways
Textbook:
Nelson, D. L. and Cox, M. M. (2021) 8th ed.
9
 Carbohydrate metabolism
Syllabus Citric acid cycle

Oxidative phosphorylation
Photosynthesis

10
Syllabus Metabolism of fatty acid and lipid
Metabolism of amino acid and nucleotide

11
v
(
)

35% 3/27 Exam1 (Ch13, 14, 15, 16)

25% 4/24 Exam2 (Ch19, 20)

40% 6/2 Exam3 (Ch17, 18, 21, 22)

12
v

13
14
Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
BST / Yi-Chun Liao 15
 Carbohydrate metabolism
Citric acid cycle
Bioenergetics Oxidative phosphorylation

and Metabolism Photosynthesis

Metabolism of fatty acid and lipid
Metabolism of amino acid and nucleotide
Bioenergetics:
The quantitative study of energy
transformations in living systems.

Metabolism:
The entire set of enzyme-catalyzed
transformations of organic molecules
in living cells.
16
 Bioenergetics and metabolism

• To obtain chemical energy by capturing solar

energy or degrading energy-rich nutrients

• To convert nutrient molecules into the cell’s

own characteristic molecules

• To polymerize monomeric precursors into

macromolecules

• To synthesize and degrade biomolecules

required for specialized cellular functions
17
 Autotroph and heterotroph

Autotroph:
An organism that can synthesize its
own carbon-containing biomolecules
from carbon dioxide.

Heterotroph:
An organism that requires complex
organic molecules, such as glucose,
as a source of carbon.

18
• Solar energy as the ultimate source
of energy for almost all cells.

• Solar energy is converted to the

chemical energy of organic molecules
by photoautotrophs.

Classification
based on:
Carbon source
Energy source

Fig. 1 on p.462 19
Fig. 1-4

20
 Metabolism

The many
reactions that
go on in the
cells of living
organisms.

Fig. 13-28 21
“Metabolism” derives from the Greek
word for “change”.

• The chemical changes that take place

in a cell or an organism.

• These changes convert nutrients into

energy and the materials that cells
and organisms need to grow, reproduce,
moving, housekeeping, and so on.

22
 Pathway
Glucose

Glycolysis

2 Pyruvate

PDC

2 Acetyl CoA

TCA
Fig. 13-28 23
 Catabolism and anabolism

Catabolism:
The energy-yielding degradation of
nutrient molecules, typically an
oxidative process.

Anabolism:
The energy-requiring biosynthesis of cell
components from smaller precursors,
typically a reductive process.

24
 Catabolism

The pathways that break down

larger molecules into smaller ones.

The set of metabolic reactions that

transform fuels into cellular energy.

Fuel (carbohydrates, fats) CO2 + H2O + useful energy

25
 Anabolism

The pathways that synthesize larger

biomolecules from smaller ones.

The set of metabolic reactions that

require energy to synthesizes
molecules from simpler precursors.

Useful energy + simple precursors complex molecules

26
Catabolism Anabolism

degradative synthetic

oxidative reductive

energy-yielding energy-requiring
(exergonic) (endergonic)

Produces ATP, uses ATP, NADPH

NADH & NADPH

27
 Products from one
provide substrates
for the other.

Many intermediates
are shared between
anabolism and catabolism.

Fig. 2 on p.462 28
 Central
pathways

29
 Central pathways
Carbohydrate metabolism
Citric acid cycle

Oxidative phosphorylation
Photosynthesis
Metabolism of fatty acid and lipid
Metabolism of amino acid and
nucleotide

Fig. 12.2 in
Mathews et al.,
Biochemistry, 4th
edition (2013) 30
Initial phase of carbohydrate catabolism
Carbohydrate metabolism
Citric acid cycle

Oxidative phosphorylation

Fig. 12.3 in Mathews et al., Biochemistry, 4th edition (2013)

Photosynthesis
Metabolism of fatty acid and lipid
Metabolism of amino acid and
nucleotide

Glycolysis

31
 Oxidative metabolism
Carbohydrate metabolism
Citric acid cycle

Oxidative phosphorylation
Photosynthesis

Fig. 12.4 in Mathews et al., Biochemistry, 4th edition (2013)

Metabolism of fatty acid and lipid
Metabolism of amino acid and
nucleotide

32
 Carbohydrate anabolism
Carbohydrate metabolism
Citric acid cycle

Oxidative phosphorylation

Fig. 12.5 in Mathews et al., Biochemistry, 4th edition (2013)

Photosynthesis
Metabolism of fatty acid and lipid
Metabolism of amino acid and
nucleotide

Gluconeogenesis

Polysaccharide
synthesis

33
 Major fate of C

a central metabolic
intermediate

Fig. 12.2 in Mathews

et al., Biochemistry,
4th edition (2013)
34
 Acetyl coenzyme A

The various building blocks

are degraded into a common
product, the acetyl group of
acetyl-CoA.
A
Coenzyme A (CoA)

Vit B5
Fig. 15.14 in Berg et al., Biochemistry, 7th edition (2012)
35
A metabolically activated 2C fragment

Fig. 3 on p.463 36
• Amphibolic pathway involves both
catabolism and anabolism.

• Anabolism and catabolism occur

simultaneously in the cell.
The cell maintains tight and separate
regulation to meet the metabolic needs
in an immediate and orderly fashion.

Competing metabolic pathways are localized

within different cellular compartments.

37
The substrate for lysine acetylation

Galdieri et al., Eukaryot Cell 13:1472-1483 (2014)

Less tightly
More tightly

DNA Acetylation

Histone

Fig. 8-41 in Watson et al., Molecular Biology of the Gene, 7th edition (2014) 38
 et : and year
alii : others volume published

Galdieri et al., Eukaryot Cell 13:1472-1483 (2014)

authors journal pages or article

number (ARTN)

Article types in scientific journal

• Reviews • News
• Research articles • Perspectives
• Reports • Communications or letters
39
 Reactions in biological systems

• Cellular chemistry does not encompass

every kind of reaction learned in a
typical organic chemistry course.

• Although thousands of different chemical

reactions occur in the biosphere, most of
them fall within a small set of reaction
types.

40
A chemist
carrying out an organic synthesis rarely
runs more than one reaction in a single
reaction vessel.

A living cell
carrying out thousands of reactions
simultaneously, with each reaction sequence
controlled so that unwanted accumulations or
deficiencies of intermediates and products
do not occur.
41
The keys to learning metabolism

• How cells carry out these rxns?

• When and where do they happen?

• How to regulate them?

42
Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
43
 Free energy: G

• Free energy, G = expresses the amount

of energy capable of doing work during
a reaction at constant temperature and
pressure. G of a closed system = H – TS

enthalpy, H = heat content, roughly reflecting the

number and kinds of bonds

entropy, S = represents the randomness or disorder

of the components of a chemical system
44
 Free-energy change: ∆G

• ∆G = ∆H − T∆S
∆H is negative for a reaction that releases heat
∆S is positive for a reaction that increases randomness
T: absolute temperature

Fig. 1-26 45
 Actual free-energy change: ∆G
• Actual free-energy changes depend on
reactant and product concentrations.
aA + bB ⇄ cC + dD
(Eqn 1-1 on p.24)

[A]i: the ini+al concentra+on of A, and so forth

R: the gas constant
T: the absolute temperature

• ∆G (the actual free-energy change) for

any chemical reaction is a function of
the ∆G° (standard free-energy change).
46
Standard free-energy change: ∆G°

• Standard free-energy change is directly

related to the equilibrium constant.
[C]eq [ D]eq
c d

aA + bB ⇄ cC + dD K eq = (Eqn 13-2 on p.468)

[ A ]eq [ B]eq
a b

At equilibrium, ∆G = 0 and

47
∆G°: delta G naught
Under standard conditions:
1 M concentration of all reactants, and
1 atm pressure

∆G’°: delta G prime naught

Under biochemical standard conditions:
[H+] is 10-7 M (pH is 7 in physiologic conditions),
[H2O] is 55.5 M, [Mg2+] is 1 mM

Delta G prime naught is just like Delta G naught

but for biology.

48
 Free-energy changes are additive

• Overall ∆G for a series of reactions is equal

to the sum of ∆G of each individual reaction.

A⇄B+C ∆G′! = +21 kJ/mol

B⇄D ∆G′! = -34 kJ/mol
A⇄C+D ∆G′! = -13 kJ/mol

A thermodynamically unfavorable reaction

can be driven by a thermodynamically
favorable reaction to which it is coupled.
49
From individual reactions to pathways

• Entire set of reactions in pathway

must be thermodynamically favored.

Metabolic pathways are formed by the

coupling of enzyme-catalyzed reactions
such that the overall free energy of the
pathway is negative.

50
The free-energy change provides
information about the spontaneity
but not the rate of a reaction.

Fig. 4-3 in Watson et al., Molecular Biology of the Gene, 6th edition (2008) 51
 ∆G and enzymes

• Enzymes cannot change equilibrium constants but

can increase the rate at which a reaction proceeds.

Figs.8.3 & 8.2 in Berg et al., Biochemistry, 7th edition (2012) 52

Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
53
A cri&cally important macromolecule—arguably
“second in importance only to DNA”—is ATP.
ATP is a complex nanomachine that serves as
the primary energy currency of the cell.
Trefil, James. 1992. 1001 Things everyone should know about science. Doubleday. New York.

54
Without ATP, life as we understand it could not
exist. It is a perfectly-designed, intricate
molecule that serves a critical role in providing
the proper size energy packet for scores of
thousands of classes of reactions that occur in
all forms of life. Even viruses rely on an ATP
molecule identical to that used in humans.
Goodsell, David S. 1996. Our molecular nature. Springer-Verlag. New York.

55
 The special role of ATP

ATP is the chemical link between

catabolism and anabolism

• Part of free energy from oxidation of

food or light energy converted into ATP.

• ATP acts as free energy donor in most

energy requiring processes.
- motion, active transport, biosynthesis

56
ATP is synthesized by 3 major routes

• Substrate-level phosphorylation

• Oxidative phosphorylation

• Photophosphorylation

57
• Substrate-level phosphorylation
The formation of ATP from ADP in which
the phosphate donor is a substrate with
high phosphoryl transfer potential or a
phosphorylated reactive intermediate.

pyruvate kinase (in glycolysis)

p.521

58
 • Oxidative
phosphorylation
mitochondrion

ATP synthase

• Photo-
phosphorylation
chloroplast

Fig. 19.25 in Berg et al.,

Biochemistry, 7th edition (2012)
59
 Cellular energy currency: ATP
Adenosine 5’-triphosphate
triphosphate adenosine

adenine

g b a glycosidic
bond

ribose
phosphoester bond
Fig. 3.4 in Garrett and Grisham,
Biochemistry. 6th edition (2017) 60
∆G for ATP hydrolysis is <0 & large

The hydrolytic cleavage of the terminal

phosphoanhydride bond in ATP relieves some
of the internal electrostatic repulsion in ATP.

Fig. 8-40

61
Fig. 13-11

62
 ATP hydrolysis is exergonic

• ATP + H2O ⇄ ADP + Pi ∆G′! = -30.5 kJ/mol

orthophosphate

• ATP + H2O ⇄ AMP + PPi ∆G′! = -45.6 kJ/mol

pyrophosphate Table 13-6

• Under cellular conditions

Partially shields the

negative charge Fig. 13-12

• ATP + H2O ⇄ ADP + Pi ∆G ~ -50 kJ/mol

63
 Actual ΔG of ATP hydrolysis

ATP + H2O ⇄ ADP + Pi

[ADP][Pi]
∆G = ∆G′! + RT ln
[ATP]

body temperature 37 C
(0.25 X 10-3)(1.65 X 10-3)
∆G = -30.5 kJ/mol + (8.315 J/mol·K)(310 K) ln
(2.25 X 10-3)
= -52 kJ/mol

64
 Uses of other ribonucleotides

• Some reactions use GTP, UTP, or CTP

• Equally high energies of hydrolysis
Adenine appears to form more readily
under prebiotic conditions; so ATP may
have predominated initially.

• nucleoside diphosphate kinase

• adenylate kinase

p.487
65
 High-energy compounds

PEP

66
 PEP hydrolysis

Fig. 13-13

67
High-energy compounds

68
• Although the breakdown of "super-high-energy"
compounds, such as PEP, is not used rou>nely
in cells to drive endergonic reac>ons, these
compounds are s>ll important because they can
be used to drive the synthesis of ATP from ADP.

• It is significant that ATP has a phosphoryl-transfer

potential that is intermediate among the
biologically important phosphorylated molecules.

69
ATP can thus act
as a phosphate
donor, and ATP
can be synthesized
by transfer of
phosphate from
other compounds,
such as PEP.

Fig. 13-19
70
High-energy compounds

71
 How does ATP provide energy?

ATP provides energy by group transfers,

not by simple hydrolysis

glutamine synthetase

Fig. 13-18 72
 Fig. 13-18

Transfer of part of the Displacement of the p-

ATP molecule to a substrate containing moiety,
molecule or to an amino acid generating Pi, PPi, or AMP
residue, activating it as the leaving group
73
• Kinase
Transfer a phosphoryl group from ATP to
an acceptor molecule (phosphorylation)

• Phosphorylase
Catalyze a reaction where phosphate attacks
and becomes covalently attached at the point
of bond breakage (phosphorolysis)

• Phosphatase
Catalyze the removal of a phosphoryl group
from a phosphate ester (dephosphorylation)
74
 Daily human need for ATP

• Adult human:
11700 kJ (2800 kcal)/day (average)

• Under cellular conditions

ATP + H2O ⇄ ADP + Pi ∆G ~ -50 kJ/mol

11700 kJ X 50%
X 551 g/mol = 65 kg ATP!!!
50 kJ/mol

75
 Mode of energy exchange
• ATP is an immediate donor of free energy,
not a long-term storage form of free energy.
• Typically, an ATP is consumed within ~1 min
of its formation.

Energy Energy

76
 ATP–ADP cycle

• Human being possess

only about 50 g of ATP
at any given moment.

• ATP is recycled
approximately
1300 times/day.

Fig. 15.8 in Berg et al.,

Biochemistry, 7th edition (2012)

77
Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
78
Reactions occur in repeating patterns

• Five general categories of rxns

in living cells:
– reactions that make or break C-C bonds
– internal rearrangements, isomerizations,
and eliminations
– free-radical reactions
– group transfer reactions
– oxidation-reduction reactions

79
- making C-C bonds

Fig. 13-4

- elimination

p.474

- isomerization

Fig. 13-6
80
- free radical

Fig. 13-1

- group transfer

Fig. 13-8
81
Oxidation-reduction (redox) reactions

• Oxidation-reduction reactions involve the loss

or gain of electrons
– one reactant gains electrons and is reduced
– the other loses electrons and is oxidized

• Oxidation reactions generally release energy

– living cells oxidize metabolic fuels
(carbohydrates, fat)

82
 Redox half-reactions

• The oxidation of ferrous ion by cupric ion,

Fe2+ + Cu2+ ⇄ Fe3+ + Cu+

can be describe in terms of two half-rxns:

(1) Fe2+ ⇄ Fe3+ + e-
(2) Cu2++ e- ⇄ Cu+

83
 Conjugate redox pair
• An electron donor and its corresponding
electron acceptor
• Redox couple X:X-
X-: reduced form X: oxidized form
Cu+ Reductant Oxidant Cu2+
NADH Reducing agent Oxidizing agent NAD+
Donor of e- Acceptor of e-

Oxidation Reduction
loss of e- gain of e-

84
 Reduction potential

• Standard reduction potential, E!

a measure (in volts) of the relative
affinity of the electron acceptor of each
redox pair for electrons
– positive value = takes electrons
– negative value = donates electrons

85
e- tends to flow from low to high E!

• Standard of reference:
half-reaction H+ + e- ⟶ ½ H2

• When any two half-cells are connected,

the half-cell with the more positive E!
is reduced
- this half-cell has the greater
reduction potential

86
 Measuring reduction potential
• e- flows from one half-cell to the other.
◼ Electrons travel through
electrodes/wires electrode
connected to a
voltmeter.

H2

◼ The agar bridge

allows ions to sample standard
move, establishing
electrical continuity.
Fig. 18.5 in Berg et al.,
Biochemistry, 7th edition (2012) 87
 • If e- flow from sample to standard,
sample has negative reduction potential.
The reduction potential of the X:X- is
the observed voltage at the start.

e- →
E! = 0 V
Negative: donate e-
e- ←
Positive: take e-

sample standard

Fig. 18.5 in Berg et al.,

Biochemistry, 7th edition (2012) 88
89
 X:X- couple
E! is negative:
e- →, negative
Lower affinity for e-
e- ←, positive
Ready to donate e-
X- is a reducing
agent.

E! is positive:
Higher affinity for e-
sample standard Ready to accept e-
X is an oxidizing
agent.
Fig. 18.5 in Berg et al., Biochemistry, 7th edition (2012) 90
Example 1 ½ O2 + 2 H+ + 2 e- → H2O
E’! = +0.816 V
Positive reduction potential
Higher affinity for e-
A strong oxidizing agent

Example 2 NAD+ + 2 H+ + 2 e- → NADH + H+

E’! = -0.32 V
Negative reduction potential
Lower affinity for e-
A strong reducing agent
91
Relationship between ∆G’° and ∆E’!

∆G° = -nF∆E’! ∆G’° : kJ mol-1

n: e- transferred
F: Faraday constant
(96.5 kJ mol-1 V-1)
∆E’! : V (volts)

92
Energy from oxidation of fuels

In aerobic metabolism, ultimate

electron acceptor is O2 and the
carbon in fuel molecules is oxidized
to CO2.

93
 Sugar + O2 CO2 + H2O

direct burning
stepwise oxidation
of sugar
Free energy

Activation/conversion
Adapted from Fig. 3 in Essentials of Cell biology, Unit 1.2, eBook from Scitable by Nature Education 94
 Rather than burning all their energy in one
large reaction, cells release the energy
stored in their food molecules through a
series of oxidation reactions.
Free energy

Activation/conversion
Adapted from Fig. 3 in Essentials of Cell biology, Unit 1.2, eBook from Scitable by Nature Education 95
Oxidation states of the C in cells

• When a carbon atom shares an electron

pair with another atom (typically H, C,
S, N, or O), the sharing is unequal, in
favor of the more electronegative atom.

• The order of increasing electronegativity

is H < C < S < N < O.

• The more electro-negative atom “owns”

the bonding electrons it shares with
another atom.
96
most reduced e- e-

Fig. 13-22 most oxidized 97

 Sugar + O2 CO2 + H2O Electron acceptor
molecules capture
stepwise oxidation some of the energy
lost from the food
- molecule during each
-
- oxidation reaction and
store it for later use.
Free energy

Electrons move from

various metabolic
intermediates to
specialized electron
carriers in enzyme-
Activation/conversion catalyzed reactions.

Adapted from Fig. 3 in Essentials of Cell biology, Unit 1.2, eBook from Scitable by Nature Education 98
 Glucose
2 ATP
Glycolysis 2 NADH

2 Pyruvate

PDC 2 NADH

2 Acetyl CoA

2 ATP
TCA 6 NADH
2 FADH2
Fig. 13-28 99
 Universal electron carriers

v For fuel oxidation

• accept e- directly from fuel
• ultimate e- acceptor: O2

v For reductive biosynthesis

100
 NAD+ and NADP+
Nicotinamide adenine dinucleotide (phosphate)

nicotinamide

adenine

R = H for NAD+
R = PO32- for NADP+ Fig. 15.13 in Berg et al.,
Biochemistry, 7th edition (2012)
101
 Oxidation by NAD+
XH2 + NAD+ → X + NADH + H+
a hydride ion (:H-)

e- released in the form

of hydride ion (H:-)

catalyzed by
dehydrogenase
(oxidoreductase)
Adapted from Fig. 13-24 102
 FAD
Flavin adenine dinucleotide

adenine

Fig. 15.14 in Berg et al.,

Biochemistry, 7th edition (2012)

103
 Oxidation by FAD
XH2 + FAD → X + FADH2

Fig. 13-27
104
 Glucose
2 ATP
Glycolysis 2 NADH

2 Pyruvate

PDC 2 NADH

2 Acetyl CoA

2 ATP
TCA 6 NADH
2 FADH2
Fig. 13-28 105
Fig. 19-1 106
 Universal electron carriers

v For fuel oxidation

v For reductive biosynthesis

• Precursors are usually more
oxidized than products.
• Reducing power is needed.

• Electron donor typically

NADPH (NADH used primarily
for ATP generation).
107
the carrier of e-
from catabolism
to anabolism

Fig. 17.2 in Garrett and Grisham,

Biochemistry. 6th edition (2017) 108
 Table 17.3 in Garrett and Grisham, Biochemistry. 6th edition (2017)
Vitamins and coenzymes

Fig. 13-26
109
 CoA

FAD

NAD+

PLP
Fig. 15.17 in Berg et al.,
Biochemistry, 7th edition (2012)

110
Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
111
 Metabolism regulated
in 3 principal ways

• The amounts of enzymes

• The catalytic activity of enzymes

• Compartmentalization

112
 The amounts of enzymes

• The amount of a particular enzyme

depends on both its rate of synthesis
and its rate of degradation.

• The amount of enzyme is controlled

primarily by changing the rate of
gene transcription.

113
 hormones, growth factors, cytokines

Fig. 13-29
114
 Metabolism regulated
in 3 principal ways

• The amounts of enzymes

• The catalytic activity of enzymes

• Compartmentalization

115
Regulating the catalytic activity

• Substrate concentration

• Binding of allosteric effectors

or regulatory proteins

• Covalent modifications

116
Fig. 13-29
117
Regulating the catalytic activity

• Substrate concentration

• Binding of allosteric effectors

or regulatory proteins

• Covalent modifications

118
 Reversible allosteric control
Regulatory
subunit

Cataly&c
subunit

Fig. 6-35 119

 Allosteric enzymes undergo
conformational changes in
response to modulator binding.

Fig. 13-29
120
Regulating the catalytic activity

• Substrate concentration

• Binding of allosteric effectors

or regulatory proteins

• Covalent modifications

121
Reversible covalent modification

Fig. 6-38

122
 Reversible covalent modification

• Occur within seconds

or minutes of a
regulatory signal

• Phosphorylation and
dephosphorylation are
most common

Fig. 13-32 123

Fig. 13-29
124
 Metabolism regulated
in 3 principal ways

• The amounts of enzymes

• The catalytic activity of enzymes

• Compartmentalization

125
 The accessibility of substrates

• Enzyme sequestration
Sequestering enzyme and its substrate
in different compartments

Fig. 15-6 126

Fig. 13-29
127
 Compartmentalization of reactions
Segregates opposing reactions
e.g., fatty acid synthesis and oxidation occurs in
different subcellular localization

Fig. 21-9 128

Introduction to Metabolism

• A first look at metabolism

• A brief review of thermodynamics
• Phosphoryl transfer and ATP
• Biological redox reactions
• Regulation of metabolic pathways
129
 Metabolome

• Metabolome is the complete set of low-

molecular-weight substances involved in
metabolism or produced by a cell or organism
under specified physiological conditions.

• Metabolomics is the systematic identification

and quantitation of all these substances.

130
 Multi-omics

Ritchie et al., Nature Reviews Genetics 16:85-97 (2015) 131

 Metabolomic analysis
• Metabolites:
A series of chemical intermediates
in the enzyme-catalyzed reactions
of metabolism.

• Mass spectrometry (MS) offers

unmatched sensitivity for detection
of metabolites at low concentrations.

• Nuclear magnetic resonance (NMR)

provides remarkable resolution and
discrimination of metabolites in
complex mixtures.
132
What can the metabolome tell us?

• The different kinds and relative

abundances of the various cellular
metabolites are the best indicator
of the phenotype of the cell.

• Any change in these metabolites

indicates that a perturbation
(a phenotypic change) has occurred,
which may be useful clinical clues.

133