Metabolism

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Metabolism

• Metabolism is about how energy is obtained,
• stored and transformed.
• Based on energy source, all life can be divided
• into
• Autotrophs - self-feeding, organisms that use
• CO2 as main carbon source.
• Heterotrophs - feeding on others, obtain energy
• by ingesting organic compounds
• such as carbohydrates and fats.

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Each can be further divided into Aerobes Live
in air and use O2 for energy production
Anaerobes - that do not require O2 to
survive. Some strict anaerobes are
allergic to oxygen.  
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Metabolic Pathway

• Metabolism relies on thousands of sequential
• enzymatic reactions.
• A series of reactions with a specific purpose is
  
• called a pathway.
• Each pathway is a cascade leading the synthesis
• or degradation of a biological compound.

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• Intermediary metabolism.
• Products from one reaction (metabolites
• or intermediates) often become the reactants
  for the next reaction.

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Metabolic pathways can be Linear, Branched, Sp
iral. Fig. 14.3 on p368.
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• Two aspects of metabolism
• Catabolism
• - Degradation path.
• - Complex organic molecules are degraded to
  simpler species.
• - Production of energy.
• Anabolism
• - Construction path.
• - Biosynthesis of more complex organic
  compounds.
• - Requires energy.

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Catabolism and anabolism are always related.
Energy produced by catabolic pathways in the
form of ATP ("energy currency"), is used in
anabolic pathways for the synthesis of new
molecules. The two processes are couple by
ATP energy cycle, and are precisely regulated
and balanced.
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Overview of Intermediary metabolism
ADP Pi
ADP Pi
ADP Pi
ATP
ADP Pi
ATP
ATP
ATP
pyruvate
urea
ADP Pi
acetyl-CoA
O2
ATP
electron transport chain oxidative
phosphorylation
e-
citric acid cycle
CO2
ATP
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• ATP adenosine triphosphate
• a nucleotide composed of three basic units.

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ATP and ADP
ADP - ATP conversions act as a major method
of transferring energy.
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Catabolic stages of metabolism

• Stage I
• Breakdown of macromolecules into their
  building blocks (glucose, a.a., fatty acids).
• No energy production.
• Stage II
• Oxidation of Stage I products to acetyl CoA.
  (Glycolysis and ?-oxidation).
• Limited energy production.
• Stage III
• Oxidation of acetyl CoA to CO2 and H2O and
  energy (Citric acid cycle).

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Overview of catabolic processes
Stage 1 Stage 2 Stage 3
Glycolysis
ATP
Pyruvate
Acetyl CoA
Citric acid cycle
Oxidative phosphorylation
ATP
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The chemistry of metabolism

• Six categories of biochemical reactions have been
• identified
• Oxidation-reduction
• Group-transfer
• Hydrolysis
• Nonhydrolytic cleavage
• Isomerization and rearrangement
• Bond formation reactions using energy from ATP

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I. Oxidation-Reduction
The major reactions involved in energy
production.
In redox reactions, electrons are transferred
from one molecule to another   AH2 B A
BH2 AH e donor or reducer B e acceptor
or oxidizer. Gaining and losing electrons are
always accompanied by gaining and losing of H,
...
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When a molecule loses electrons, it is oxidized.
When a molecule gains electrons, it is reduced.
Its easier to follow the movement of H. A
molecule with H added is reduced. A molecule
with H removed is oxidized.  
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For example NAD (a coenzyme, oxidized
form) NADH (reduced form)
  Enzymes that catalyzes the redox reactions are
called ? 
Dehydrogenases.
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Oxidation levels of a carbon atom in an organic
molecule can also be monitored by watching the
O atom numbers bond to the C center. CH4
represents the least oxidized level CO2
represents the highest oxidized level (Read T
14.3!)
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• Many redox reactions are coupled to the coenzyme
  pairs.
• NAD / NADH
• NADP / NADPH
• FAD / FADH2

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• For example,
• CH3CH2OH NAD CH3CHO NADH H
• In the reaction from ethanol to acetic acid,
• NAD is serving as electron acceptor or oxidizing
• agent, so that ethanol can be oxidized into
  acetic
• acid.

alcohol dehydrogenase
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(No Transcript)
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Oxidation -, gaining oxygen or loss of H atoms
(each H has 1 e and 1 H) Reduction, loss of
oxygen or gaining H atoms.
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To monitor a redox reaction, its easier to
follow the movement of H. A molecule with H
added is reduced. A molecule with H removed is
oxidized.  
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For a carbon atom, the most oxidized form is
CO2 The most reduced form is CH4. Oxidation
of C could be C 2O ? CO2 Or - CH3 ? CH2
H (1e- and 1 H) In oxidative phosphorylation
electrons and H travel separately.
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II. Group-Transfer

• Intermolecular Transfer of a functional group
  from one molecule to another.
• Intramolecular Movement from one location to
• another on the same molecule.
• Enzymes isomerases and transferases (kinase,
  glycosylase)

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The most frequently transferred group in
metabolism is phosphate group. The attachment
of P-group to a molecule is also called
phosphorylation.
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• Other groups transferred include acetyl and
  glycosyl (carbohydrate) groups.
• Addition of a glycosyl group is called
• glycosilation.

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III. Hydrolysis

• Large molecules are broken down to small
• molecules due due to the participation of H2O.
•  

The chemical forces that are broken by H2O
molecules include ester bonds, amide bonds, and
glycosidic bonds. Enzyme hydrolases (amylase,
peptidase, esterase)
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Hydrolysis of ester bonds releases fatty acids
from a triacylglycerol to release energy.  
Hydrolysis of amide bonds (or peptide bonds)
breaks proteins into oligopeptides, dipeptides
or amino acids.   Hydrolysis of glycosidic bonds
by glucosidases (amylase, cellulase, lactase)
can break down polysaccharides into disaccharides
or monosaccharides.
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Hydrolysis of Carbohydrates
(maltose)
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Hydrolysis of peptide bonds
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IV. Nonhydrolytic cleavage

• Molecules are split without H2O.
• The enzymes involved are Lyases.

C
O
O
H
C
aldolase
C
H
HO
C
O

C
HO
H
C
H
HO
C
H
HO
fructose-1,6- dihydroxyacetone
glyceraldehyde bisphosphate
phosphate 3-phosphate
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V. Isomerization and rearrangement(Isomerases)

•  Two major isomerizations
• 1.    Intramolecular H shifts changing the
  location
• of double bond.
• For exp., aldose-ketose isomerization
•  

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Glyceraldehyde 3-phosphate and dihydroxy-lacetate
are both three-carbon sugars
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 2. Intramolecular rearrangement of phosphate
group, an important step in glycolysis
Glucose 6-phosphate and glucose 1-phosphate.
(mutases isomerases)  
Galactose G 1-P G 6-P pyruvate
phosphoglucomutase
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VI. Bond formation by using energy Enzymes
ligases or synthetases
Fig. 14.11
citrate
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For the names and functions of different classes
of enzymes, study T14.2 on p372.
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Standard Free Energy Change ?G free energy
change ?Go free energy change under standard
condition (1 atmosphere at 25oC, solute
concentration 1M). ?Go' Standard free energy
change when pH 7 It defines the difference
b/w the energy content of products and the
energy content of reactants under standard
condition.
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A B C D Keq C D A
B Keq, the equilibrium constant under
standard condition. ?Go - 2.303RT logKeq R,
the gas constant 8.315 J/mol T, the absolute
temperature 298K (corresponding to 25oC)
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By knowing the sign and value of ?Go, one
can predict whether a reaction under standard
condition is thermodynamically favorable or not
and how much energy is released or required.
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Experimental measurement of ?Go
For the reaction glucose 6-P fructose
6-P When reach equilibrium, G 6-P 1.33M, F
6-P 0.67 M. Keq F 6-P / G 6-P 0.67
/ 1.33 0.5 ?Go - 2.303RT logKeq -
2.303 (8.315) (298K) log 0.5 1718 J/mol
1.718 kJ/mol (p382)
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Table 14.5

• ?Go 0 System at equilibrium, no release or
  requirement of energy.
• ?Go lt 0 Reactants have higher energy level.
• Reaction releases energy as it approaches
  equilibrium.
• ?Go gt 0 Reactants have lower energy level.
• Reaction requires that energy be added to
  proceed in the direction indicated.

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If a reaction is favorable under standard
condition (releasing energy) the ?Go' value
will be negative. If a reaction is
thermodynamically unfavorable, the ?Go' value
will be positive.   For exp., a reaction with
?Go' of 100 kJ/mol is more favorable than the
one with ?Go' of 10 kJ/mol.
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• In the isomerization reaction of G 6-P and F 6-P,
  ?Go 1.7 kJ/mol.
• This indicates that energy is required for
  glucose-6-phosphate to be converted to
  fructose-6-phosphate -- it is not spontaneous.

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The hydrolysis reaction of ATP has ?Go' as 30.5
(p383). The negative ?Go' value indicates that
the hydrolysis of ATP is a spontaneous reaction,
or a thermodynamically favorable reaction.
  In this reaction, products ADP and Pi are at a
lower energy level than reactants ATP and H2O,
so energy is released when ATP is changed into
ADP.      
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Fig. 14.12.
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A reaction with - ?Go' value is said to be
exergonic. A reaction with ?Go' value is
said to be endergonic. In metabolism, all
catabolic reactions are exogernic all anabolic
reactions (biosynthesis) are endergonic.
energy released by an exergonic reactions is
used to facilitate an endergonic reactions.
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Overview of catabolic metabolism
ADP Pi
ADP Pi
ADP Pi
ATP
ADP Pi
ATP
ATP
ATP
pyruvate
urea
ADP Pi
acetyl-CoA
O2
ATP
electron transport chain oxidative
phosphorylation
e-
citric acid cycle
CO2
ATP