Reginald H.

Garrett
Charles M. Grisham
[Link]/chemistry/garrett

Chapter 17
Metabolism: An Overview

Reginald Garrett & Charles Grisham • University of Virginia

Essential Question

• What are the anabolic and catabolic

processes that satisfy the metabolic needs of
the cell?

Anabolic means
"building up"
catabolic means
"breaking down."
17.1 Is Metabolism Similar in Different
Organisms?
• Organisms show remarkable similarity in their
major metabolic pathways
• This is evidence that all life descended from a
common ancestral form
• And yet, living things also exhibit metabolic
diversity
• Note the classification of organisms in Table 17.1
• Oxygen is essential for aerobes, but obligate
anaerobes are poisoned by oxygen
• The flow of energy in the biosphere and the
carbon and oxygen cycles are intimately related
• The impetus driving the cycle is light energy.
The Sun is Energy for Life
• Phototrophs are “photosynthetic organisms” use light to
drive synthesis of organic molecules

• Chemotrophs use organic compounds such as glucose or,

in some instances, oxidizable inorganic substances Fe2+,
NH4+, elemental sulfur as sole sources of energy.

• Heterotrophs require an organic form of carbon, such as

glucose, in order to synthesize other essential carbon
compounds.

• Autotrophs are organisms that can use just carbon dioxide

as their sole source of carbon
17.1 Is Metabolism Similar in Different
Organisms?

• Autotrophs use CO2;

• Heterotrophs use organic carbon;
• Phototrophs use light;
• Chemotrophs use organic and inorganic
electron donors
1. Aerobic: use oxygen as electron accepter in energy production

2. Obligate Aerobic: Organisms for which O2 is obligatory or

compulsory for life.

3. Anaerobic: can subsist without Oxygen

4. A facultative anaerobic: an organism is an organism that makes

ATP by aerobic respiration if oxygen is present, but is capable of

switching to fermentation if oxygen is absent

5. Obligate Anaerobic: are poisoned by oxygen

Figure 17.1 The flow of energy in the biosphere
is coupled to the carbon and oxygen cycles
The primary source of energy for life is
the sun. Photoautotrophs utilize light
energy to drive the synthesis of
organic molecules, such as
carbohydrates, from atmospheric
CO2 and water.

Heterotrophic cells then use these

organic products of
photosynthetic cells both as fuels and
as building blocks, or precursors, for
the biosynthesis of their own unique (Figure 17.1).
complement of biomolecules.
Ultimately, CO2 is returned to the
atmosphere for reuse by the
photoautotrophs
17.2 What Can Be Learned From Metabolic
Maps?

Figure 17.2 A metabolic map,

indicating the reactions of
intermediary metabolism and
the enzymes that catalyze
them. More than 500
different chemical
intermediates, or metabolites,
and a greater number of
enzymes are represented
here.
17.2 process of metabolism
• Metabolism consists of catabolism and anabolism
• Catabolism:
1. degradative pathways
2. Usually energy-yielding
3. are characteristically energy-yielding
4. involves the oxidative degradation of complex nutrient
molecules
• Anabolism:
1. biosynthetic pathways
2. Usually energy-requiring
3. are characteristically energy-requiring
4. is a synthetic process in which the varied and complex
biomolecules are assembled from simpler precursors
17.3 How Do Anabolic and Catabolic Processes
Form the Core of Metabolic Pathways?

• Metabolic maps; portray the principal reactions of

intermediary metabolism
• When the major metabolic routes are known and their
functions are understood, the maps become easy to follow,
in spite of their complexity
Figure 17.6 Anabolism and Catabolism are
Interrelated
Products from one
provide substrates for
the other.

Many intermediates are

shared between anabolism
and catabolism.
Anabolism and Catabolism Are Not Mutually
Exclusive

• Catabolic pathways converge to a few end

products
• Anabolic pathways diverge to synthesize
many biomolecules

Amphibolic

• Some pathways serve both in catabolism and

anabolism
Comparing Pathways
• Anabolic & catabolic pathways involving the
same product are not the same

• Some steps may be common to both

• Others must be different - to ensure that each

pathway is spontaneous/thermodynamically
favorable
• This also allows regulatory mechanisms to turn
one pathway on and the other off
The Pathways of Catabolism Converge to
a Few End Products
What are three stages of
catabolism?
Stage 1: Proteins,
polysaccharides, and lipids
are broken down into their
component building blocks.

Stage 2: The building blocks

are degraded into the
common product, the acetyl
groups of acetyl-CoA.

Stage 3: Catabolism
converges to three principal
end products: water, carbon
dioxide, and ammonia.
Metabolic Regulation Requires Different Pathways
for Oppositely Directed Metabolic Sequences

Figure 17.8 Parallel pathways of catabolism and anabolism must differ in at

least one metabolic step so that they can be regulated independently.
Shown here are two possible arrangements of opposing catabolic and anabolic
sequences between A and P.
(a) Parallel sequences proceed by independent routes.
(b) Only one reaction has two different enzymes.
ATP Serves in a Cellular Energy Cycle
• ATP is the energy currency of cells

• Phototrophs transform light energy into the

chemical energy of ATP

• In heterotrophs, catabolism produces ATP,

which drives activities of cells

• ATP cycle carries energy from

photosynthesis or catabolism to the energy-
requiring processes of cells
Figure 17.9 The ATP Cycle in Cells
ATP is formed via photosynthesis in phototrophic cells
or catabolism in heterotrophic cells.

Energy-requiring
cellular activities are
powered by ATP
hydrolysis, liberating
ADP and Pi.
The Substrates of Catabolism Contain Relatively
Reduced Forms of Carbon

Figure 17.10 Comparison of the state of reduction of carbon

atoms in biomolecules. Chains of –CH2- groups are the
most energy-rich form of reduced carbon in the
biosphere. Carbon dioxide is the final product of catabolism
and the most oxidized form of carbon in the biosphere.
Nicotinamide adenine dinucleotide (NAD+)
Collects Electrons Released in Catabolism
• The substrates of catabolism – proteins,
carbohydrates, and lipids – are good sources of
chemical energy because their carbon is reduced
• The oxidative reactions of catabolism release
reducing equivalents from these substrates, often
in the form of hydride ions
• These hydrides are transferred to NAD+
molecules, reducing them to NADH
• NADH in turn passes these reducing equivalents
to other acceptors
• The ultimate oxidizing agent, O2, is the final
acceptor of electrons, becoming reduced to H2O
NAD+ Collects Electrons Released in
Catabolism

Figure 17.11 Hydrogen and electrons released in the course of

oxidative catabolism are transferred as hydride ions (H:-) to
the pyridine nucleotide, NAD+, to form NADH + H+ in
dehydrogenase reactions.
NADPH Provides the Reducing Power for
Anabolic Processes
• Catabolism is oxidative, anabolism is reductive

• Biosynthesis typically relies on reducing

equivalents from NADPH

• NADPH can be viewed as the carrier of electrons

from catabolic reactions to anabolic reactions

• In photosynthesis, light energy is used to pull

electrons from water and transfer them to NADP+
• O2 is a by-product of this process
NADPH Provides the Reducing Power for
Anabolic Processes

Figure 17.12 Transfer of

reducing equivalents
from catabolism to
anabolism via the
NADPH cycle.
17.4 What Experiments Can Be Used to
Elucidate Metabolic Pathways?
• Eduard Büchner (late 19th century) showed that
fermentation of glucose in yeast cells yielded
ethanol and carbon dioxide can occur in the
broken yeast cells

• This led to a search for intermediates of glucose

breakdown

1. Metabolic inhibitors were important tools for

elucidating the pathway steps.

2. Mutations also were used to create specific

metabolic blocks
17.4 What Experiments Can Be Used to
Elucidate Metabolic Pathways?

Figure 17.13 The use of inhibitors to reveal the sequence

of reactions in a metabolic pathway. (a) Control. (b) Plus
inhibitor. Intermediates upstream of the metabolic block (B,
C, and D) accumulate, revealing themselves as
intermediates in the pathway. The concentration of
intermediates lying downstream (E and F) will fall.
Isotopic Tracers Can Be Used as
Metabolic Probes
• Metabolic pathways have been elucidated by use
of isotopic forms of elements

• Metabolic substrates and intermediates can be

“labeled” with a measurable isotope and then
“traced” through a series of reactions

• Two types of isotopes have been used in this way

1. Radioactive isotopes, such as 14C and 32P

2. Stable “heavy” isotopes, such as 18O and 15N
Isotopic Tracers Can Be Used as
Metabolic Probes
Figure 17.14 One of the earliest experiments using a radioactive isotope
as a metabolic tracer. Melvin Calvin found that 3-phosphoglycerate (PGA)
is the first metabolite labeled when algae are incubated with radioactive
CO2.
NMR Spectroscopy is a Noninvasive
Metabolic Probe
• The nuclei of certain atomic isotopes have
magnetic moments
• Such nuclei can absorb radio-frequency energy in
the presence of a magnetic field at a unique
resonant frequency
• The nuclear magnetic resonance (NMR)
absorption is influenced in predictable ways by
the chemical nature of its neighboring atoms and
by its dynamic behavior (motion)
• For these reasons, NMR signals can provide a
wide range of structural and dynamic information
about biomolecules
NMR Spectroscopy is a Noninvasive
Metabolic Probe

Figure 17.15 The metabolism of a living subject can be

observed in real time with NMR spectroscopy.
Metabolic Pathways are
Compartmentalized Within Cells

Figure 17.16
Fractionation of a cell
extract by differential
centrifugation.
Metabolic Pathways are Compartmentalized
Within Cells

Figure 17.16
continued.
Fractionation of
a cell extract by
differential
centrifugation.
Metabolic Pathways are Compartmentalized
Within Cells

Figure 17.17 Compartmentalization of

glycolysis, the citric acid cycle, and
oxidative phosphorylation.
 17.5 What Can the Metabolome Tell Us About a
Biological System?
• The metabolome is the complete set of low-
molecular weight molecules present in an organism
and excreted by it under a given set of
circumstances
• Metabolomics is the systematic identification and
quantitation of all these metabolites in a given
organism or sample
• Mass spectrometry (MS) and nuclear magnetic
resonance (NMR) are both powerful techniques for
metabolomic analysis

• MS offers unmatched sensitivity for detection of

metabolites at low concentrations

• NMR provides remarkable resolution and

discrimination of metabolites in complex mixtures
Figure 17.18 Mass spectrometry offers
remarkable sensitivity for metabolomic analyses.
17.6 What Food Substances Form the
Basis of Human Nutrition?
• Protein is a rich source of nitrogen and also
provides essential amino acids
• Carbohydrates provide needed energy and
essential components for nucleotides and
nucleic acids
• Lipids provide essential fatty acids that are key
components of membranes and also
important signal molecules
• Fiber – whether soluble or insoluble – can be a
beneficial component in the human diet