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Cells and Their
Housekeeping
Functions – Metabolic
Process and ATP
Shu-Ping Lin, Ph.D.
Institute of Biomedical Engineering
E-mail: [email protected]
Website: http://web.nchu.edu.tw/pweb/users/splin/
Date: 11.17.2010
Degradation of Glucose
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Glucose metabolism:
C6H12O6 + 6O2  6CO2 + 6H2O + energy
Blocks indicate 4 separate pathways in cellular energy
process, each pathway is composed of multiple
consecutive reactions catalyzed by enzyme. 
Anaerobic Respiration
Glycolysis in cytoplasm, others in mitochondria (called (Respiration without O2)
cellular respiration)
Glycolysis: consists of 10 reactions to convert glucose
into 2 molecules of 3-carbon compounds (i.e. pyruvic
acid and pyruvate)
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First 5 reactions consume energy: 2 ATP molecules are
used to phosphorylate and activate glucose to 3-carbon
sugar phosphate
Aerobic Respiration
nd
2 set of reactions: hydrogen atoms are removed (Respiration using O2)
(oxidation) by NAD+ forming NADH (reduction):
2NAD+2 + 4H (oxidation)  2 NADH (that’s a total of 4
e-) -- Four ATP were produced from energy released by
substrate-level phosphorylation
Exergonic process with ∆G = -140kcal/mol
Glycolytic pathway do not involve oxygen
Glucose+ 2Pi+ 2ADP+ 2NAD+  2 pyruvate+ 2ATP+ 2NADH+ 2H++ 2H2O
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Glycolysis is highly regulated.
blood to meet the need for ATP.
Cells acquire enough glucose from
Citric-Acid Cycle (Aka Krebs Cycle)
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Begins when acetyl CoA combines with oxaloacetate (a 4-C molecule) to
produce citric acid and releases Coenzyme A
Each turn of the citric acid cycle consumes one acetyl CoA molecule
(originally a pyruvate, since glycolysis produces 2 pyruvates, 1 glucose
molecule produces 2 turns of the citric acid cycle )
One turn of the Krebs cycle oxidizes the remaining citric acid, or citrate,
producing 1 ATP, 3 NADH, 1 FADH2, and the byproduct 2 CO2 which is
exhaled
Glucose Metabolism
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The citric-acid cycle of glucose produces: 4 CO2, 2 ATP,
6 NADH, 2H+, and 2 FADH2
Glucose+ 2Pi+ 2ADP+ 2NAD+  2 pyruvate+ 2ATP+ 2NADH+ 2H++ 2H2O
2X
2X
2X
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Respiratory Chain
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FADH2 & NADH are energy carriers and
used to produce ATP. Couple
oxidization of NADH or FADH2 to produce
ATP
1
NADH  H   O2  NAD   H 2O
2
Intermembrane space
G  52.4
Matrix
ADP  Pi  nH P  ATP  nH N
kcal
mol
Oxidization of NADH by oxygen is
exergonic. (Hydrolysis of ATP=-12kcal/mol)
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Occur on inner membrane of
mitochondria (capable of rapid electronexchange, i.e. oxidation & reduction) and
involve sequential transfer of electrons
through membrane-associated molecules
http://www.life.illinois.edu/crofts/bioph354/lect10.html
Electron-transport system (ETS): high energy electron-carrying enzyme
deliver electrons to more electronegative enzyme  Each successive carrier is
more electronegative than the last so electrons are pulled downhill  One
carrier reduces another, energy released is used to pump hydrogen ions
across the membrane into the intermembrane space  Remaining energy is
used to reduce the next carrier
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ElectonsETSSynthesize ATP
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Proton (H+) accumulate in the intermembrane space  Cause
concentration gradient and charge gradient across membrane
Concentration gradient forces protons to pass channel protein ATP
synthase  Relaxation of the proton flux couples formation of ATP.
Free-energy change (△G) in transporting uncharged molecule from
concentration 1 to 2 is: (R:gas constant=1.987 cal/mol, T:absolute
temperature in Kelvin= 273.15 °+ ℃)
G  RT ln( C 2 )
C1
Membrane electric potential and ion concentration gradient provide
driving force for moving ions (charged particles) across membrane. 
△G of transporting ion might be large enough to drive other processes.
(Z:electrical charge of transported species, △V:potential in volts(V) across
membrane 12, F:Faraday constant=23.062 kcal/Vmol )
G  RT ln( C 2 )  ZFV
C1
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ATP Synthase
ATP synthase catalyzes the formation of
ATP Proton-conducting unit F0 spans the
lipid bilayer. ATP synthesizing unit F1 faces
matrix. Hydrogen flow form intermembrane
space to matrix through F0. 3 catalytical β
subunits of F1 are structurally identical but in
different configurations at any particular point
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Catalytic site in open (O) form
(configuration): little affinity for substrates
Loose (L) form: bind to either ATP or
ADP+Pi loosely and is catalytically inactive
Tight (T) form: bind to either ATP or
ADP+Pi tightly and is active
Energy input from proton flux
converts T site to O site O site to
L site L site to T site: New L site
binds new ADP and phosphate
and begins a new reaction sequence
Proton flux: not needed in ATP from
ADP+Pi, but can release tightly
bound ATP and cycle continues
△G<0 in intermembrane space 
Flow protons through ATPase and
ADP+Pi bind to ATPase  Enzyme
catalyzes formation of ATP  ATP
detaches from ATP synthase when
proton flux
http://www.sigmaaldrich.com/life-science/metabolomics/learning-center/metabolic-pathways/atp-synthase.html
http://www.sigmaaldrich.com/sigma-aldrich/areas-of-interest/life-science/metabolomics/learning-center/metabolic-pathways/atp-synthase/atp-animation.html
Summary of Glycolysis
and Cellular Respiration
Respiratory
Chain:
Anaerobic Respiration
(Respiration without O2)
4ATP+10NADH
+ 2FADH2=
(4+ 3X10+ 2X2)
= 38 ATP
Total Yields
Aerobic Respiration
(Respiration using O2)
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Mitochondria are highly efficiently as energyprocessing plants.
Glucose 2 pyruvates + 2 ATP (in cytoplasm)
Pyruvates imported into mitochondrion and
oxidized by O2 to produce 30 ATP (3ATPX10=30;
since NADH 3ATP molecules, FADH2
2ATP molecules)
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Photosynthesis
Photosynthesis: anabolic reaction, convert light energy to
chemical energy of organic compounds – raw materials: water,
carbon dioxide (CO2, inorganic) and energy (sunlight)
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Products: glucose (energy rich carbon compounds) and
oxygen (side product)
http://en.wikipedia.org/wiki/Photosynthesis
6CO2 + 12H2 O + energy  C6H12O6 + 6H2 O + 6O2
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H2O: used as reactant and released as a product
2 pathways: driven by light energy in 1st pathway;
entrapment of energy received from photons into ATP
molecules in subsequent pathway  Light: radiant
energy (packets of photons)
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E=h c/ λ (E:energy, c:3x1010cm/s, h:Planck’s constant
1.584x10-34cal s)
λ:400~700nm; violet (high “E”), blue, green, yellow,
orange, red
Energy of molecule absorbing photon rises from ground
state to excited state and drives electrons to away from
nucleus Loosely held electron then get transferred to
other molecules in subsequent reactions, resulting in
the production of ATP from ADP Common to the
degradation of glucose
http://www.overidon.com/wpcontent/uploads/2010/06/wavelength-light1.jpg
Common Themes in Metabolic Pathways
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Central themes of metabolism:
1)
2)
3)
4)
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ATP is the universal currency of energy. Hydrolysis of ATP increase equilibrium ratio
of products to reactants in energy-requiring reaction by a factor of about 108.
ATP is generated by the oxidation of fuel molecules such as glucose. Chemical
energy in carbon bonds using electron carriers to create proton gradient across inner
membrane of mitochondria to synthesize ATP.
Metabolic pathways generate ATP and transfer high-potential electrons to
electron carriers such as NADH also provide building blocks for macromolecules.
Biosynthetic and degradative pathways are almost always separate and utilize
different enzymes. Biosynthetic pathway is made exergonic by hydrolysis of ATP.
Recurring motifs in these reactions
1)
2)
3)
Flow of molecules down metabolic pathway is determined by amounts and
activities of certain enzymes. First irreversible reaction in metabolic pathway is
committed step Enzymes catalyzing committed steps are typically regulated by the end
product.
Regulatory enzymes in metabolic pathway are controlled by
phosphorylation. Proteosomes control protein concentration by degradation.
Metabolic pathways involve compartmentalization of chemical reactions.
Whether they are in cytoplasm or in mitochondria, compartmentalization is a useful
tool in separating degradative pathways from biosynthetic pathways.