Chapter 15

Metabolism: Basic
Concepts and
Design

© 2019 W. H. Freeman and Company

1
 Ch.15 Learning Objectives

By the end of this chapter, you should be able to:

1. Explain what is meant by intermediate metabolism.
2. Identify the factors that make ATP an energy-rich
molecule.
3. Explain how ATP can power reactions that would
otherwise not take place.
4. Describe the relationship between the oxidation
state of a carbon molecule and its usefulness as a
fuel.
5. Describe the recurring motifs in metabolic
pathways.

2
 Cells Extract Energy from their Environment
and Use the Energy for a Host of Biological
Activities including Biosynthesis
• Basic principles govern energy manipulations in all cells:
–
X
Molecules are degraded or synthesized stepwise in a series of
reactions termed metabolic pathways.

–I ATP is the energy currency of life and it couples exergonic with

endergonic pathways.

–Y ATP can be formed by the oxidation of carbon fuels.

–N Although many reactions occur inside a cell, there are a limited

number of reaction types involving particular intermediates that
are common to all metabolic pathways.

–A Metabolic pathways are highly regulated.

–↓ Enzymes involved in metabolism are organized into large

complexes

⑪ The reactions of energy extraction and energy use are called metabolism or intermediary
metabolism.

3
 Section 15.1 Metabolism Is
Composed of Many Coupled,
Interconnecting Reactions
• Energy is required to
1. power muscle contraction and cell movement,
2. active transport, and
3. biosynthesis.

• Phototrophs obtain energy by capturing sunlight.

• Chemotrophs obtain energy through the oxidation of
carbon fuels produced by phototrophs

4
 Metabolism Consists of Energy-yielding
and Energy-requiring Reactions
• Metabolic pathways can be divided into two types:
near ne

1 ->
• Catabolic pathways combust carbon fuels to synthesize ATP.

2 -
• ⑤
Anabolic pathways use ATP and reducing power to
synthesize large biomolecules.
Anabolic Include the
:

Grebs cycle as a source

of the crop cycle

of these
making one

intermediaries so that
• Some pathways, called amphibolic pathways, can function
anabolically or catabolically.
,
be look
the Intermediary cen -> :

used in the animal .

• Although anabolic and catabolic pathways may have reactions

in common, the regulated, irreversible reactions are always
h

distinct.
-

chemical reactions given cell in given living organism

* Metabolism is all the
in a a :

fuels ATP
1) Catabolic pathway it down carbon break
synthesize
S 2)
.

to
:

biomulecules
syntesige large
⑧

from to
.

AtP and reduce

patway
Anabolie NADPH
:

poweruse
make ATP SO
down of few molecules to harvest energy to ,

the breaking building ;

of that ATP to reactions where the cell will be
then it can topple the breaking protein the v3
large biomolecules as DNA , RNA
synthesizing For example
.

,
will be
,
.

the
fabrication
is the two regions
.

Amphipate
: of

to
Note :

Some reaction are joins

be common with comor pathway
opposite reaction
,
in
that can so
Example break downs
:

Glycolysis
Glugose
↓
link to
Glugose
Glycolysis 5
 -

Glucose Metabolic Pathways

Metabolism

Only use 5 -> break

glucose and down
glycogen Faits
tr and

Ap Production protein
without N

oxysen P takes
energy from the http://www.genome.ad.jp/kegg
ene metabolic
Carbohydrate
·

Achieve’s Metabolic Map Pathway fuels

large molecules
.

fattyacidsad.
are

doing step by step .

lintied reactions
by
.

FIGURE 15.1 Glucose metabolism. Glucose is metabolized to pyruvate in 10 linked reactions. Under
anaerobic conditions, pyruvate is metabolized to lactate and, under aerobic conditions, to acetyl CoA.
The glucose-derived carbons of acetyl CoA are subsequently oxidized to CO2.
FIGURE 15.2 Metabolic pathways. Each node represents a specific metabolite. [From the Kyoto
Encyclopedia of Genes and Genomes (www.genome.ad.jp/kegg).]

A Metabolism is essentially a sequence of chemical reactions that begins with a particular molecule and
results in the formation of some other molecule or molecules in a carefully controlled process.
A There are many interconnected pathways in every cell. These are interdependent and very closely
coordinated.

Achieve’s Metabolic Map is listed in our course in Achieve.

pontaneous order to function ,

* Metabolism the chemicals reactions has to be in
is going to happen
reaction
present
, .

in the cellular organism the

;

as
long the enzyme
thermodinamically favorable unfavable couple
.

because is
it will help
thermodynamically
to ⑧

,
chemical reaction is
*
key aspect helps when the
:

6
 Reaction Thermodynamics
• ∆G for the formation of products C and D from
substrates A and B is given by

rig
=>
Products

Reactants
↓
->

360
298
A Thermodynamically Unfavorable Reaction Can Be Driven by a Favorable Reaction

· in a metabolic pathway :
a reaction with A

t Do can occur if
coupled
to a reaction with a

Greater-DG .

* A reaction can occur spontaneously only if ∆G, the change in free energy, is negative.
A The ∆G of a reaction depends on the nature of the reactants and products (expressed by the ∆G°′
term, the standard free-energy change) and on their concentrations (expressed by the second term).
Al To construct a metabolic pathway, two criteria must be met:
1.The individual reactions must be specific.
2.The pathway in total must be thermodynamically favorable.
A thermodynamically unfavorable reaction in a pathway can be made to occur by coupling it to a more

test
!
G favorable reaction. In the example below, the two reactions are coupled by their use of the same
intermediate “B.”
I 11
11 V
v
V will
unfavorable reaction it
hey as sect :

if there is an
thermodynamically
favorable reactions that the energy released
,

thermodynamical
so
le with other reaction
Cop
,
C
favorable reaction Can be used to power up
thermodynamically
by thewell the non-spontaneous
reactions that
as these reaction so to be absorbed by ,

Energy activate and the reaction can take

place .

the hydrolysis of AtP drives

the Formula
it the reaction
·

is equilibrium ,
the cell is not taking place , meaning
it use
.

·
with others
might change drastically by becoming favorable couple
.

even

* D6'under cellular Conditions will

favorable
reaction favorable under Cellular conditions it needs to be coupled to a .

* if a
is not
,

7
 Section 15.2 ATP Is the Universal Currency
of Free Energy in Biological
ritrogenous
Systems base

will
adenosine
N

E
*Samma
of
*
the
hydrolysis
the most
release enough
energy to provide
-
6
I

gamma is
the
energetic favorable
X
=> necessary .

Glycosidie bound
.

energy for
reactions i n
many -
ribose
.

* the sis of
metabolic properties 3 phosphate nucleotide
-

by droly structure
beta wil↓ also release
energy .
8

Structures of ATP, ADP, and AMP

ATP Hydrolysis Is Exergonic

common

Si
Favorable
n =
under stander condition
->
Favorable 5
unFavorable -
only gamma
.

no common
Hydrolyses I
all 3

Phosphate
⑧ Adaneintere
higher
>
under cellular conditions is approx. −50 kJ mol-1 (−12 kcal mol−1) -

G test ! transfer of ATP .

FIGURE 15.3 Structures of ATP, ADP, and AMP. These adenylates consist of adenine (blue), a ribose
(black), and a tri-, di-, or monophosphate unit (red). The innermost phosphorus atom of ATP is
designated Pα, the middle one Pβ, and the outermost one Pγ.

A Energy derived from fuels or light is converted into adenosine triphosphate (ATP), the cellular energy
currency.
D Much of the free energy that is derived from the oxidation of food molecules (primarily carbohydrates
and fats) is transformed into ATP, which acts as the free-energy donor in most energy-requiring
processes such as motion, active transport, and biosynthetic reactions.
A
The hydrolysis of ATP is highly exergonic because the triphosphate unit contains two
-> negative Favorable
phosphoanhydride bonds that are unstable.
=

A The actual ∆G for ATP hydrolysis under cellular conditions depends on many factors, but is
approximately −50 kJ mol-1 (−12 kcal mol−1).

metabolic General exergonie because contain all the

*
pathway are considered as a
pathway in ,
it
to be able
energy as whole ma
king exergonie · there will some
pathways where it have to invest energy
toharestwoveeverp like:Glycolysis t use hyhelige totmodify moleatesenou set tothepoint fee

8
 Some Biosynthetic Reactions Are
Driven by the Hydrolysis of Other
Nucleoside Triphosphates

de
intercovertible via a
they can

Particular enzymes present in the

Cell

D The ATP/ADP cycle is an important means of energy exchange in biological systems, but some
reactions are driven by other NTPs–GTP, UTP, or CTP. transfer of phosphate from AtP by meet dipho kinases
·

D Enzymes can catalyze the transfer of a terminal phosphoryl group from one nucleotide to another.

* Some cell can require Stp instead of ATP .

Atp =

hydrolyzes = GTP =
GTP stays !

it a partwarcatabolicreactereleases stoit isequivalentto obte

·

vare e

9
 ATP Hydrolysis Drives Metabolism
by Shifting the Equilibrium of
Coupled Reactions
• Consider the following endergonic reaction:
-

K′eq = [B]eq/[A]eq = e−ΔG∘′/2.47 = 1.15 × 10−3

• Coupling this reaction with ATP hydrolysis renders the

it
formation of B exergonic. Adding energy to change
->
.

10
 The High Phosphoryl Potential of ATP
Results from Structural Differences between
ATP and its Hydrolysis Products
etwertre car ene

• energ
ATP has a high phosphoryl-transfer
potential because of four key factors:
1. Resonance stabilization
2.
3.
4.
Electrostatic repulsion
Increase in entropy
Stabilization by hydration
3 the factors
hydrolysis
thermo dinamically
I
favorable .
in
of
the

B Phosphoryl-transfer potential is a means of comparing the tendency of organic molecules to transfer a

phosphoryl group to an acceptor molecule.
A Example: ATP has a higher phosphoryl-transfer potential than glycerol 3-phosphate. Gamma is removed =>

to be transfer .

A The high phosphoryl-transfer potential of ATP can be explained by its structure.

being removed but covalent bond is broten making that phosphoryl

④
thSensrats
I St hory)
C >
ferred to
group is
something else .
,

to become
stable Corthophosphate) It
I helps
.

more
.

=>

negative charge
be removed
because they have
make easie t o
the
phosphate to
repeal bound is broken
they
=

and having the same signal

.

the molecule breaking it's

increased of entropy (th Favorable)
.

The bond breaking

an
=> ;

will have those

negative
because it water
hydration
;

moth
will be further stabilized by bounding
=> the orthophosphate will be inmediately associated via hydrogen
charges that phosphate
molecules .

* the reverse reaction will be unfavorable .

11
 Resonance Structures of Orthophosphate

Improbable Resonance Structure for ATP

FIGURE 15.4 Resonance structures of orthophosphate.

FIGURE 15.5 Improbable resonance structure. The structure contributes little to the terminal part of
ATP, because two positive charges are placed adjacent to each other.

D Orthophosphate, one of the products of ATP hydrolysis, has greater resonance stabilization than do
any of the ATP phosphoryl groups.
D An improbable resonance structure for ATP has two adjacent positive charges. ATP has fewer

resonance forms than an orthophosphate does.

12
 Phosphoryl-transfer Potential is an Important
Form of Cellular Energy Transformation

# breaking Atp is
thermodynamicall synthesis of AtP
favorable reaction A
Al

that release
is thermodynamically
unFavorable reaction
a

of
good Compounds with High Phosphoryl-Transfer Potential require just
amount
that will
energy as much
to
energy
.

take
place

I
.

hee
have

the cell use

ADP- ATP thesetheeit

ATP

FIGURE 15.6 Compounds with high phosphoryl-transfer potential. The role of ATP as the cellular
energy currency is illustrated by its relation to other phosphorylated compounds. ATP has a
phosphoryl-transfer potential that is intermediate among the biologically important phosphorylated
molecules. High-phosphoryl-transfer-potential compounds (1,3-BPG, PEP, and creatine phosphate)
derived from the metabolism of fuel molecules are used to power ATP synthesis. In turn, ATP donates
a phosphoryl group to other biomolecules to facilitate their metabolism. [Data from D. L. Nelson and
M. M. Cox, Lehninger Principles of Biochemistry, 5th ed. (W. H. Freeman and Company, 2009), Fig. 13-
19.]

* ATP has a phosphoryl-transfer potential that is intermediate between high phosphoryl-potential

compounds derived from fuel molecules and acceptor molecules that require the addition of a
phosphoryl group for cellular needs.
–Example: in glycolysis, ATP is generated when ADP receives a phosphate from a donor that
has an even higher phosphoryl-transfer potential (1,3-bisphosphoglycerate,
phosphoenolpyruvate).
–Example: creatine phosphate serves as a reservoir of high-phosphoryl-transfer potential
phosphate groups in vertebrate muscle. We use this molecule to regenerate ATP when we
exercise strenuously.

13
 Sources of ATP during Exercise
&

Creatine
phosphate
of
:

ATP ,
t
muscle
cell
is a source
it is more sustained
the
,

need it in ->
of
moment Atp decreases
longterm type
exercise
.

↳
⑧
Creatine
phosphate
Serves as G

reservoir for high

->
ATP
energy
phosphate de
Group
from
.

Comes
and
glycolysis
Fermentation .

hydrogen ↓
used .

· Creatine Base
Catalyzesthe reaction-
ATP - ADP ·

FIGURE 15.7 Sources of ATP during exercise. In the initial seconds, exercise is powered by existing
high-phosphoryl-transfer compounds (ATP and creatine phosphate). Subsequently, the ATP must be
regenerated by metabolic pathways.

A The ATP concentration in many cells is much higher than the KM of typical ATP-binding enzymes,
suggesting that ATP may play additional roles in the cell.
⑪ Recent research suggests that ATP is a hydrotrope; it is amphipathic, but the hydrophobic component
(the adenine in this case) is too small to self-aggregate.
A It is believed that ATP helps to keep cellular proteins, which are at quite high concentration, in
solution. This helps to prevent the formation of protein aggregates in the cell.

14
 Section 15.3 The Oxidation of Carbon Fuels *

by reducing
Carbon feels
Is an Important Source of Cellular Energy
,

they are

Free Energy of Oxidation of Single-carbon Compounds rich

energy .

Most reduce ->

is oxidase
->
Glugose CO2
all the to

way
·

Glucose : a
is
Prominent Fuels
moting Ho it requires more

It will
steps
our fuel hydroly ses .
more

,the energy th gre er o

.

major .
takes a

than
burn the fatty aid glucose
FIGURE 15.8 ATP–ADP cycle. This cycle is the fundamental mode of energy exchange in biological
systems.
FIGURE 15.10 Prominent fuels. Fats are a more efficient fuel source than carbohydrates such as
glucose because the carbon in fats is more reduced.

A ATP is the immediate donor of free energy for biological activities. However, the amount of ATP is
limited.
⑪ Consequently, ATP must be constantly recycled to provide energy to power the cell.
A Oxidation reactions involve a loss of electrons. Such reactions must be coupled with reactions that gain
electrons. The paired reactions are called oxidation–reduction reactions or redox reactions.
A In aerobic organisms, the carbon atoms in fuels are oxidized to yield CO2, and the electrons are
ultimately accepted by oxygen to form H2O.
A The more reduced a carbon atom is, the more free energy is released upon oxidation.
A Fats are a more efficient food source than glucose because fats are more reduced.

* Intermediaries
Food is
of metabolism of glucose ,
will help to cell make tip
by the
eating .

15
 Oxidation of Glyceraldehyde 3-phosphate
Coupled to Production of ATP in Glycolysis Takes
Place over Several Steps

1 2

3
Reduction of

fergh
->

yes a bet
I
&Phosphate
3
transfer
Oxidation
to
.

dr *elps to be
erg efficient the
*
⑧ ADP > to > ATP
↑
steps
-

came from energy

released due to the App-> to -> ATP
Interaction between
molecules

** The essence of catabolism is capturing the energy of carbon oxidation as ATP.

A Oxidation of the carbon atom may form a compound with high phosphoryl-transfer potential that can
then be used to synthesize ATP.
A
Example: the energy released when carbon 1 (shown in red) of glyceraldehyde 3-phosphate is oxidized
can be captured first as 1,3-bisphosphoglycerate and then as ATP.

A Hydrogen phosphate ion

A Now 1,3-BPG, which has higher phosphoryl transfer potential
A This is facilitated by an enzyme – substrate level phosphorylation

16
 Ion Gradients across Membranes Provide
an Important Form of Cellular Energy that
Can Be Coupled to ATP Synthesis

Proton Gradients

they produces -

Vesicles that ,
Membrane transport :

they can add

the cell takes
Protor pumps .
advantage of
form
by gradients
bacteria crossmenBe either
themselves power up
other
ATPase the transport of
molecules in eo-

W
transport .

FIGURE 15.11 Proton gradients. The oxidation of fuels can power the formation of proton gradients by
the action of specific proton pumps (yellow cylinders). These proton gradients can in turn drive the
synthesis of ATP when the protons flow through an ATP-synthesizing enzyme (red complex).

⑪ Ion gradients can couple endergonic reactions with exergonic reactions.

A In animals, 90% of ATP is generated when the energy of a proton gradient is coupled with ATP
synthesis in the process of oxidative phosphorylation.

17
 Phosphates Play a Prominent Role
in Biochemical Processes
• Phosphates are important chemicals in biochemical
reactions because they are thermodynamically unstable
while being kinetically stable. The kinetic stability is due
to the negative charges that resist hydrolysis unless
assisted by enzymes.
• The combination of thermodynamic instability and kinetic
stability allows the enzyme-catalyzed use of phosphate
esters for energy transformations as well as regulation.

18
 Energy from Foodstuffs is Extracted
X

to
not
be
always
glucose
in Three Stages
has
to

form ATP
eat
The food that

I
.

we
3
.

Interconvert
I Intermediaries .

what we eat
into something that
can be funneled into

cell respiration Reactions ->

1 ->
here at
f
allows the
conversion
to
Convert ->
of that stuff
Stages of Catabolism CoA
Acetyl
.

2
fell retation .

FIGURE 15.12 Stages of catabolism. The extraction of energy from fuels can be divided into three
stages.

The generation of energy from food occurs in three stages:

1.Large molecules in food are broken down into smaller molecules in the process of digestion.
2.The many small molecules are processed into key molecules of metabolism, most notably
acetyl CoA.
3.ATP is produced from the complete oxidation of the acetyl component of acetyl CoA.

19
 Electron Carrier ! ->
Oxidation reduction
* if the
electrons of
not

Section 15.4 Metabolic Pathways that molecules a re

transferred would
,
break
down and c a u s e a
lot

Oxidation reduction
the electrons of the
Contain Many Recurring Motifs of damage .

molecules are soing to be

removed
Electron ① -

⑳
Carriers
removedtobetransferent
->
>

use in metabolism .

⑪
↓
transfer to a n electron
protein carrier the
.

being
-> removed ·
to
reduceeu e

Hydrogens
are
to be
-

removeds .
release together .

with the NADH

NAD takes both ⑳

:

Structures of the Oxidized Forms of

Electron
hydrogen ,
to
Nicotinamide-derived Electron Carriers
Carries later on

FAD : takes both all

Pron and atoms .
By B
· Anabolic
Process
By us
En NADPH

Structures of the Reactive ↑

Components of FAD and FADH2

Structure of the Oxidized Form of

Flavin Adenine Dinucleotide (FAD)

FIGURE 15.13 Structures of the oxidized forms of nicotinamide-derived electron carriers.

Nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+)
are prominent carriers of high-energy electrons. In NAD+, R = H; in NADP+, R = PO32−.
FIGURE 15.14 Structure of the oxidized form of flavin adenine dinucleotide (FAD). This electron
carrier consists of a flavin mononucleotide (FMN) unit (shown in blue) and an AMP unit (shown in
black).
FIGURE 15.15 Structures of the reactive components of FAD and FADH2. The electrons and protons
are carried by the isoalloxazine ring component of FAD and FADH2.

D Activated carriers exemplify the modular design and economy of metabolism.

A Example: ATP is an activated carrier of phosphoryl groups.
A Other activated carriers are common in biochemistry, and they often are derived from vitamins.
A NADH/NAD+ and FADH2/FAD are activated carriers of electrons for fuel oxidation.
A NADH/NAD+ participates in reactions such as the following:
*
FADH2/FAD participates in reactions such as the following:

take in anabolism
* Anabolism the reactions that need electrons
: to
place
ADPH
in
biosynthesis will involve an .

20
 Activated Carriers Exemplify the Modular
Design and Economy of Metabolism
• NADPH/NADP+ is most often the electron carrier for
reductive biosyntheses. Anabolic reaction
↓

– Example: two molecules of NADPH are required for

the reduction of a keto group to a methylene group
in fatty acid synthesis.

Anabolism
*
:

Use NADPH

21
 Coenzyme A (CoA or CoA-SH) is an
Activated Carrier of Acyl Groups such as
the Acetyl Group
-> Sulfate will react wilh
:
-

two Carbon compound

coming from pyruvate
coming from blood follicle:
So
,
that will be use a s
sulfate of two Carbon
Carrier
so then
it car
Acetyl
-
,

be taken to the brebs

CritTallism .

COA Cer thishelltowat

Cy
it

favorable .

↓
Favorable .

Coenzyme
A

Pnuovins

eli
The Transfer of the Acyl Acyl groups
activated !
Group is Exergonic because fatty acids a re

the Thioester Is Unstable

FIGURE15.16 Structure of coenzyme A (CoA-SH).

A An acetyl group is a two-carbon unit, while an acyl group is a longer unit such as a fatty acid tail.
A Acyl groups linked to CoA are important in both
A The terminal sulfhydryl group in CoA is the reactive site.
A Acetyl CoA has a high acetyl-group-transfer potential.

22
 Common Activated Carriers
• Two characteristics are common to activated carriers:
1. The carriers are kinetically stable in the absence of specific catalysts.
2. The metabolism of activated groups is accomplished with a small
number of carriers.

23
 Many Activated Carriers are Derived
from Vitamins

e
• The B vitamins
function as
Pyrator
E

coenzymes, normally
after some chemical
modification.
↓
Source of vary
Important evenzymes
.

The harmonic
reactions .

* Vitamins are the source of

coenzymes .

will not react

* if don't have the vitamin , coenzymes
.

you
not
will be Atp to run .

24
 Structures of Some of the B
Vitamins

A These vitamins are often referred to as water-soluble vitamins because of the

ease with which they dissolve in water.

FIGURE 15.17 Structures of some of the B vitamins.

25
 they not use or turn on

Zoengy mes

Noncoenzyme
Vitamins
*
do not 5

Pertenace here

A Vitamins A, C, D, E, and K
play a variety of
important roles but do
not serve as coenzymes.

Vitamin = is an it is in the blood

coenzyme elotting cascade ,
,

Vitamin in the reduced form is necessary for the b

enzyme
in
that is joins to carboxylate
the residue glutamate
Prothrombin .

26
 Key Reactions Are Reiterated
throughout Metabolism
• Although thousands of reactions constitute metabolism,
they fall into only six categories.

3
Es
oxidation
need to
trans fercises knac it .

s hydrolasses

IPases
5) Pomerases

6)
Agases

27
 1. Oxidation–reduction reactions

• Two examples from the citric acid cycle:

Remember what oxidation and reduction actually are: H atoms – electron – transfer.

28
 2. Group transfer reactions

• Example: phosphorylation of glucose in the first step of

glycolysis

Transfer of a functional group from one molecule to another

29
 3. Hydrolytic reactions

• Example: cleavage of peptide bonds in proteins

Cleavage of bonds by the addition of water

30
 4. Carbon bond cleavage by means other than
hydrolysis or oxidation, with two substrates
yielding one product or vice versa
• Examples: cleavage of a hexose in the fourth step of glycolysis and
dehydration of 2-phosphoglycerate in the ninth step of glycolysis

When H2O or CO2 are a product, a double bond is formed.

31
 5. Isomerization reactions

• Example: isomerization of citrate to isocitrate in the citric

acid cycle

Rearrangement of atoms to form isomers

32
 6. Ligation reactions that form bonds by
using free energy from ATP cleavage
• Example: the ATP-dependent formation of a carbon–
carbon bond to lengthen pyruvate into oxaloacetate

Oxaloacetate can then be used in the citric acid cycle, in gluconeogensis, or in other pathways.

33
 Metabolic Processes Are Regulated in
Three Principal Ways
Homeostasis

&

Energy Charge Regulates Metabolism

FIGURE 15.19 Homeostasis. Maintaining a constant cellular environment requires complex metabolic regulation
that coordinates the use of nutrient pools. [Information from D. U. Silverthorn, Human Physiology: An Integrated
Approach, 3rd ed. (Pearson, 2004), Figure 22-2.]
FIGURE 15.20 Energy charge regulates metabolism. When the energy charge is high, ATP inhibits the relative rates
of a typical ATP-generating (catabolic) pathway and stimulates the typical ATP-utilizing (anabolic) pathway.

Metabolic pathways must be regulated to create homeostasis (a stable biochemical environment).

* To maintain homeostasis, the levels of available nutrients must be constantly monitored and metabolism adjusted
to meet the biochemical needs of the cell.
D Homeostasis is maintained by three crucial regulatory strategies:
1. Controlling the amounts of enzymes
-

The amount of a particular enzyme depends on both its rate of synthesis and its rate of degradation.
>
The level of many enzymes is adjusted by a change in the rate of transcription of the genes encoding them.
2. Controlling catalytic activity
-

Catalytic activity is regulated allosterically or by covalent modification. Allosteric control is particularly rapid.
-

Hormones coordinate metabolic relations between different tissues, often by regulating the reversible
modification of key enzymes.
-

The energy status of the cell is often an important regulator of enzyme activity. Two common means are used to
assess energy status: energy charge and phosphorylation potential.
3. Controlling the accessibility of substrates
->
Opposing reactions can occur in different cellular compartments.
–Example: fatty acid oxidation occurs in the mitochondrial matrix, while fatty acid synthesis occurs in the
cytoplasm.
D Controlling the flux of substrates between compartments can be used to regulate metabolism.

34
 Aspects of Metabolism May Have
Evolved from an RNA World

• The fact that ATP, NADH, FADH2, and coenzyme A all

contain adenosine diphosphate units may be a reflection
of the role of RNA in early metabolism.
• In the postulated RNA world, RNA served both as a
catalyst and as an information storage molecule.

35