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10/28/2012
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Chapter 17
Metabolism: An Overview
Dr Khairul Ansari
Metabolism
•Metabolism- sum of the chemical changes that convert nutrients
•What are the anabolic and catabolic processes that satisfy the
metabolic needs of the cell?
•Is metabolism similar in different organisms?
•Prominent metabolic pathways are virtually ubiquitous among
organisms.
•Living organisms exhibit metabolic diversity
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Autotrophs use CO2; Heterotrophs use organic carbon; Phototrophs
use light; Chemotrophs use organic and inorganic electron donors
Metabolic diversity
•Classification based on carbon source- e.g. (a) Autotrophs (b)
Heterotrophs
•Classification based on energy source- e.g. (a) Phototrops (b)
Chemotrops
Metabolic diversity
•Prokaryotes are more diverse than eukaryotes
•Prokaryotes can be
-chemoheterotrophic
-Photoautotrophic
-Photoheterotrophic
-chemoautotrophic
•No Protists are chemoautotrophic
•Fungi and animals are exclusively chemoautotrophic
•Plants are mostly photoautotrophic with heterotrophic
exception.
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Oxygen in Metabolism
- Aerobes
- Anaerobes
Obligate aerobes- Homo sapiens
Facultative anaerobes- E coli
Obligate anaerobes-Clostridium (associated with food
poisoning)
•.
The Sun is Energy for Life•Phototrophs use light to drive synthesis of organic molecules
•Heterotrophs use these as building blocks
•CO2, O2, and H2O are recycled
Figure 17.1 The flow of energy in the biosphere is coupled to the carbon
and oxygen cycles
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Calcium Carbonate-A biological sink of CO2
Ca2+ + 2HCO3
- = CaCO3 + H2CO3
H2CO3= H20 + CO2
H2O + CO2 → Carbohydrate + O2
O2 is reduced to Water
CO2 is released to atmosphere
Solar energy is converted to chimerical energy
What can be learned from metabolic maps?
•Portray the principal reactions of the intermediary metabolism of
carbohydrates, lipids, amino acids and their derivatives.
•How do anabolic and catabolic processes form the core of
metabolic pathways?
•What experiments can be used to elucidate metabolic pathways?
•What can the metabolome tell us about a biological system?
•What food substances form the basis of human nutrition?
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•What can be learned from metabolic maps?
•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
•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
17.2 What Can Be Learned From Metabolic Maps?
•Metabolism consists of catabolism and anabolism
•Catabolism: degradative pathways
•Usually energy-yielding
•Anabolism: biosynthetic pathways
•Usually energy-requiring
•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
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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 What Can Be Learned From Metabolic Maps?
•One interesting transformation of the metabolic map represents each intermediate as a black dot and each enzyme as a line
•In this way, more than a thousand enzymes and substrates are represented by just two symbols
•A dot connected to a single line must be a nutrient, a storage form, an end product, or an excretory product
•A dot connected to just two lines is probably an intermediate in one pathway and has only one fate in metabolism
•A dot connected to three represents an intermediate that has two metabolic fates
17.2 What Can Be Learned From Metabolic Maps?
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17.2 What Can Be Learned From Metabolic Maps?
17.2 What Can Be Learned From Metabolic Maps?
Figure 17.3 The metabolic map as
a set of dots and lines. The
heavy dots and lines trace the
central energy-releasing
pathways known as glycolysis and
the citric acid cycle.
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•Pathways consist of sequential steps
•The enzymes may be separate
•Or may form a multienzyme complex
•Or may be a membrane-bound system
•New research indicates that multienzyme complexes are
more common than once thought
Organization in Pathways
Alternative Models Can Provide New Insights Into
Pathways
Figure 17.4 (a) The traditional view
of a metabolic pathway is
metabolite-centric.
(b) Julia Gerrard has proposed that a
protein-centric view is more
informative for some purposes.
(c) A simplified version of the
protein-centric view where proteins
in the pathway form multifunctional
complexes. (see next slide)
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Alternative Models Can Provide New Insights Into
Pathways
A simplified version
of the protein-centric
view where proteins
in the pathway form
multifunctional
complexes.
Multienzyme Systems May Take Different Forms
Figure 17.5 Schematic
representation of types of
multienzyme systems
carrying out a metabolic
pathway. (a) Physically
separate, soluble enzymes
with diffusing intermediates.
(b) A multienzyme complex.
Substrate enters the complex
and becomes bound and
then modified by E1 to E5. No
intermediates are free to
diffuse away.
(c) A membrane-bound
multienzyme system.
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17.3 How Do Anabolic and Catabolic Processes Form
the Core of Metabolic Pathways?
• Catabolic pathways are characteristically energy-yielding
• Anabolic pathways are characteristically energy-requiring
• Catabolism involves the oxidative degradation of complex nutrient molecules- resulting formation of simpler molecules
• Catabolic reactions are usually exergonic in nature (energy is stored in ATP, NADH, NADPH etc)
• Anabolism is a synthetic process in which the varied and complex biomolecules are assembled from simpler precursors
• Generally endergonic in nature (consumed stored energy from ATP, NADH, NADPH etc)
Figure 17.6 Anabolism and Catabolism are Interrelated
Products from one provide
substrates for the other.
Many intermediates are
shared between anabolism
and catabolism.
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Anabolism and Catabolism Are Not Mutually
Exclusive
• Catabolic pathways converge to a few end products
In aerobic catabolism the end products are mostly CO2, H2O and NH4
In 1st stage of aerobic catabolism the macromolecules breakdown to
their building blocks
In 2nd stage building blocks degraded to limited set of simpler product
In 3rd stage the end products mostly CO2, H2O and NH4 are produced
• Anabolic pathways diverge to synthesize many biomolecules
• Some pathways serve both in catabolism and anabolism
• Such pathways are amphibolic
• Cell tightly regulates both Catabolic and anabolic pathways
• Catabolic and anabolic pathways often localized within different
cellular compartments
Comparing Pathways
• Anabolic & catabolic pathways involving the same product are not the same
� E.g. Acetyl-Co-A is produced by both anabolic & catabolic pathways
� Several intermediates of TCA cycle and many metabolites serve both in anabolic & catabolic pathways
• 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
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The Pathways of Catabolism Converge to a Few End
Products
Figure 17.7 The 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.
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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.
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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.
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
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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
•Whereas 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
•Oxidation reactions are exergonic in nature and energy released is
coupled with ATP formation by oxidative phosphorylation
•NAD+-NADH acts as shuttle that carries electron released from
catabolic substrates to mitochondria where they are transferred to O2
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NADPH Provides the Reducing Power for Anabolic
Processes
•Whereas catabolism is fundamentally an oxidative process, anabolism
is, by its contracting nature reductive
•Biosynthesis begins with oxidized substances such as CO2.
•When glucose is synthesized from CO2 during photosynthesis
reducing power (NADPH) is required
•NADPH is generated when NADP+ is reduced with electron from
hydride ion. In heterotrophs these electrons are removed from fuel
molecule by NADP+ specific dehydrogenases
•During photosynthesis the light energy is used to pull the electrons
from water and transfer them to NADP+ , O2 is by-product
Figure 17.12 Transfer of reducing equivalents from
catabolism to anabolism via the NADPH cycle.
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Vitamins and Metabolism
In addition to NADPH and NADP+ several small molecules (nutrients
and vitamins) are essential for metabolism
•Vitamins are not synthesized by cell
•Supply externally from food
•Either water or fat soluble
•Except Ascorbic acid (Vitamin C) , most of the water soluble
vitamins are coenzymes
•Coenzymes acts as carrier of specific functional group (such as
methyl or acetyl)
•Coenzymes modified in those reactions are converted back to its
natural forms by enzymes – small amount is required
A Summary of Vitamins and Coenzymes Discussed
Elsewhere in the Text
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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
• This led to a search for intermediates of glucose breakdown
• Metabolic inhibitors were important tools for elucidating the pathway steps.
• 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.
Inhibition or mutation of an enzyme accumulates its subtract and may
that may cause (a) Lethality (b) Toxicity to the organism
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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
– Radioactive isotopes, such as 14C and 32P
– Stable “heavy” isotopes, such as 18O and 15N
– Heavy isotopes endow the compounds in a way that they appear with slightly greater mass and can be separated using mass spectrometry.
Isotopic Tracers Can Be Used as Metabolic Probes
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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
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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.
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Metabolic Pathways are Compartmentalized Within
Cells
Figure 17.16
continued.
Fractionation of a
cell extract by
differential
centrifugation.
Figure 17.17 Compartmentalization of glycolysis, the citric acid cycle, and oxidative
phosphorylation.
Metabolic Pathways are Compartmentalized Within
Cells
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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.
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17.5 What Can the Metabolome Tell Us About a Biological
System?
Figure 17.19 NMR
provides remarkable
resolution and
discrimination of
metabolites in complex
mixtures.
(a) One-dimensional
NMR of 26 small-
molecule standards.
(b) Two-dimensional
NMR of the same set
of standards overlaid
on an aqueous
extract of Arabidopsis
Fluxomics
• The true phenotype of a cell depends not only on knowledge of all the metabolites in a cell at any given moment, but also on information about the flow of metabolites through its metabolic network
• The quantitative study of metabolite flow, or flux, is termed fluxomics
• The fluxome is all of the metabolic fluxes in a metabolic network
• It thus represents systems-level information on those cellular processes defined by the metabolic network
• The fluxome is a dynamic view of the metabolic processes in a cell or organism
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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