Metabolism

Edhi Rianto
Dept. of Biochemistry
Medical Faculty Airlangga University
Learning objectives
After finishing the course the students should be
able to:
1. Explain the organization of biochemical
reactions within the cell into catabolic and
anabolic pathways
2. Explain the biochemical and energetical
characteristics of catabolic and anabolic
pathways
3. Mention high energy substances used by the
cell to drive energy-requiring processes
4. Explain the principles of ATP generation
within the cell
5. Explain how anabolism is linked to catabolism
6. Explain the outline of TCA cycle and its role in
ATP generation in aerobic respiration as well as
its amphibolic role
7. Explain how metabolism is regulated in the cell
Living and non-living matters

The universe is basically composed of living and

non-living matters

Main characteristics that differentiate living matters

(organism) from non-living matters are:
Major elemental constituents of molecules of
living matters (biomolecules) are C, H, O, and,
in some biomolecules, also N, S, and P
Biomolecules are much more diverse and
complex than molecules of non living matters
Non-living matters tend to become disarrayed
when exposed to energy (e.g. fading colours of
clothing materials exposed to sunlight,
decaying leftover foodstuffs, etc.)
On the other hand, living matters need, and use,
energy to maintain the integrity of their
structure, to grow and reproduce, and to
respond to environmental changes
Living matters are able to extract energy from
the environment and transform it into useful
energy forms that can be used to make
substances they require, and to do various
energy-requiring processes necessary for the
maintenance of life.
Biomolecules
Though extremely diverse in nature, the various
biomolecules do not burden organisms with
logistical complexity since they are structured in
an orderly, hierarchical fashion and made from
relatively simple building units
In the hierarchy various large molecules
(macromolecules, some of them polymers) are
actually constructed of or made from a limited
sort of “building-unit” molecules or monomers
Building-unit molecules themselves are made
from relatively small, simpler molecules
 Biomolecular hierarchy

Macromolecule/ Polysacharides Nucleic acids

Protein Fat*
polymer (amylum, (DNA, RNA)
glycogen, etc)
Building-block/ Fatty acid,
Amino acid Monocaharide Nucleotide
monomer glycerol

*Fat is included in this hierarchical ranking though its molecular size/molecular weight
actually does not allow it to be classified as macromolecule
Cellular energy source

Cells have to carry out thousands of chemical

reactions to maintain their proper function and
sustain life
Most of these reactions need energy, but where
does the energy come from?
Cells have diverse energy source and highly
efficient metabolic systems to convert acquired
energy into useful energy forms. The specific
mechanism vary among different cell types/
organisms.
Plant cells and cyanobacteria use light energy
and transform it into chemical energy (ATP)
through photosynthesis
Chemolitotrophic bacteria derive their required
ATP by oxidizing inorganic substances
Human and animals oxidize organic substances
in catabolic pathways to fulfill their ATP
requirement
Exergonic and endergonic reactions
Thermodynamically, there are two types of
(bio)chemical reaction:

 Exergonic reaction
 Releases free energy
 Occurs spontaneously

 Reactions in catabolic pathways are exergonic

 Endergonic reaction
 Only proceeds if driven by supplied energy
 Anabolic pathways are endergonic
Exergonic reactions
• Reactants have more free energy than the products
• Involve a net release of energy and/or an increase in
entropy
• Occur spontaneously (without a net input of energy)

Reactants

Amount of
energy
released
Free energy

(∆G <0)

Energy

Products

Progress of the reaction

Exergonic reaction: energy released

Endergonic Reactions
• Reactants have less free energy than the products
• Involve a net input of energy and/or a decrease in
entropy
• Do not occur spontaneously

Products

Amount of
energy
Free energy

released
(∆G>0)
Energy
Reactants

Progress of the reaction

Endergonic reaction: energy required

 Energy supplied

Energy
Product
must be
supplied.
Energy released

Reactant Reactant Energy is

released.

Product
Endergonic Exergonic
Energy Coupling
• For every endergonic reaction to take place, there
must be an input of free energy to drive it
• Free energy can be obtained by directly coupling an
exergonic reaction to an enderegonic reaction
• More commonly the coupling is indirect: energy
released by exergonic reactions is captured and
used to make ATP from ADP and Pi
• ATP can be broken back down to ADP and Pi,
releasing energy to power the cell’s endergonic
reactions
• This way, ATP acts as the “energy currency” that can
flexibly be used for various “energy transactions”
Direct coupling: for every endergonic reaction to take place,
there must be an exergonic reaction coupled to it where free
energy released by the exergonic reaction is used to drive the
endergonic reaction
 Heat

─P

Chemical
̴P energy

Indirect coupling: free energy released in an endergonic reactions

is captured in high energy substance (e.g.ATP) to be used to drive
various endergonic reactions
Metabolism
 Metabolism comprises the entire set of chemical
reactions occuring in a living organism that allow it
to reproduce, develop, maintain its structure and
respond to the environmental changes
 Metabolic reactions within the cell usually proceed
in sequences of biochemical reactions called
metabolic pathways
 Most of the biochemical reactions in metabolic
pathways are catalyzed and controlled by enzymes
 Metabolic pathways are divided into catabolic
pathways, anabolic pathways, and amphibolic
pathways
Catabolism
 Catabolism is the degradative phase of metabolism
in which large organic nutrient molecules (carbo-
hydrates, fats, and proteins) are converted into
smaller, simpler end products (e.g. lactic acid,
CO2, NH3).
 The degradative processes of catabolism release
energy (exergonic).
 Some of which is conserved in the formation of
ATP and reduced electron carriers (NADH, FADH2).
These reduced electron carriers can further be oxi-
dized in the respiratory chain to generate more ATP
 Not all of free energy released in each reaction step
in the catabolic cascade is transformable into ATP
or into reduced electron carriers.
Catabolic pathways (example)

Glycogen Triacylglycerol (“fat”)

Glucose Fatty acid

Glycolysis b-Oxidation

Pyruvate Lactate

Acetyl-CoA Acetyl-CoA

TCA
cycle
Anabolism

Anabolism (also called biosynthesis) is the synthetic

part of metabolism where substances are synthesized
from their precursors
Reactions in anabolic pathways are endergonic:
they neeed and use energy to proceed
Anabolic pathways (example)

Glucose Palmitate
(fattyacid)
Glycerol

Gluconeogenesis
Fatty-acid synthesis
Phosphoenolpyruvate

Acetyl-CoA

TCA
cycle
Catabolism-anabolism coupling
How can anabolic pathways be linked to catabolic path-
ways so as to enable anabolic pathways to take place?
 The main purpose of catabolism is to provide energy
for anabolism, and also to derive substances to be used
as precursors for the synthetic processes in anabolism
 Energy released in certain steps of catabolic reaction
cascade is trapped and conserved as high energy
substances, mostly as ATP, and in reduced substances
(NADH, FADH2)
 Reduced substances, when certain specific conditions
are met, are further oxydized in the respiratory chain
to generate more ATP
 ATP generated is subsequently used as “universal
biological energy currency” than can be flexibly used to
drive various anabolic reactions and to do work (e.g.
locomotion)
 Catabolism-anabolism coupling is not merely used
for energy channeling; catabolism also provides
precursor substances for many synthetic processes in
anabolism, e.g.
o Acetyl-CoA produced in carbohydrate
catabolism is the precursor substance for fatty-
acid sythesis
o Amino acid alanine, after being catabolized to
pyruvate, is the chief glucogenic substance for
the synthesis of glucose
o Glycerol, the product of fat breakdown,
like pyruvate, can be converted to glucose

 The TCA cycle (Krebs cycle), besides important for

ATP generation, is the main connecting metabolic
pathway that channels catabolic products into
anabolic synthetic processes
TCA cycle
ATP (Adenosin triphosphate)
 As implied by its name, ATP is a nucleotide consisting
of adenine base, ribose sugar and 3 phosphate groups

 The terminal phosphate group is bound to the second

phosphate with a high-energy chemical bond. When
this bond is broken as occurs when ATP is hydrolized
to ADP and phoshate, high energy is released and
used to drive endergonic reactions
ATP (Adenosin triphosphate)
 It is in this substance that the cell store free energy
released by exergonic reactios of catabolism
 It is the versatile universal energy currency of the
cell, capable of diffusing into the many cellular
compartments to the site where exergonic
reactions and phosphate-requiring reactions take
place
 Its high energy phosphate bond when enzimatic-
ally hydrolyzed releases large amount of free
energy, enabling endergonic reactions of cata-
bolism to take plece and powering other energy-
requiring processes, like active transport across
membranes, locomotion, signal transduction, etc.
Synthesis of ATP:

 The third phosphate group in ATP molecule is bound

to the second phosphate by high-energy bond
(pyrophosphate bond)

 Reaction to join this third phosphate to ADP to

make ATP is highly endergonic (requires energy)

ADP + Pi + energy  ATP

ATP synthesis is carried out via 2 mechanisms
 Substrate level phosphorilation
In substrate-level phosphorilation, high-energy phos-
phate bond is removed from substrate and directly
transferred to ADP, driven by energy released by
phosphate removal itself, resulting in the production of
ATP.
 Oxidative phosphorilation
In oxidative phosphorilation, reducing substances
produced by catabolic pathways and carried by NADH
and FADH2 are propagated by electron carrying
substances along the respiratory chain in mitochondrial
inner membrane. This electron propagation process
propells proton (H+) from mitochondrial matrix into
mitochondrial intermembranous space, creating
electrochemical gradient between the two compartments
ATP (Adenosin triphosphate)
Synthesis of ATP (contd): oxidative phosphorilation
Please re-read this excerpt over and over again

thank you.

Good luck to all of you !