BCH 210 *340

BCH219 B1OENERGETICS
STRUCTURE OF MITOCHONDRION

chain is functioning inside the mitochondria. The

The clectron ransport harng theouter And innar
membranes
!hiiochvuurions a Sudceliula1 viyaiiello in its permeability,
membrane is highly selective
cnclosing thc matrix. The inner specifically localized
specifiç transport proteins. Certain enzymes are
containing
The inner membrane contains the respiratory chain and
in mitochondria.
translocating systerms.

Outer tnembrne

IDner n1cnbrane

Lnteronbre

Muris

Cristue

Fig : Mitochondrion
TRANSPORT CHAIN
!.

THE ELECTRON component of cellular respiration,

chain (ETC) is a critical tiiphosphate
The electron transport generate enErgy ln the form.of adenosine
eukaryotic. cellsand
ceils
å pivcess by whicn the inner mitochondrial membrane of of the
(ATP). It takes place in prokaryotic cells.Here's a simplified overview
the plasmajmembrane of
electron transport chain:

Carrier Molecules: carrier molecules

1. Electron protein complexes and electron
series of molecules include
The ETCinvolves a mitochondrial membrane. These carrier dinucleotide
embedded inthe inner (NADH) and flavin adenine
dinucleotide
nicotinanmidei adenine high-energy electrons..
(FADH). Thcse molecules carry
 Complex I,
2. Complexcs: complexes, often labeled as
consists of several protein complex has specific roles in
The ETC Each
Complex III, and Complex IV.
Complex I,
and protons.
the transfer of electrons
I or
3. Electron Flow:
and FADH, enter the ETC at Complex
NADH cellular
High-energy èlectrons from they were generated in carlier stages of
how
Complex II, depending on
respiration.

4. Electron Transfer:
flow from one carrier molecule to the
through the ETC, they
As electrons nove each transfer.
next, losing energy with
5. Proton Pumping: (hydrogen
complexes, they actively pump protons
the matrix
As electrons move
through
mitochondrial membrane from themitochondrial known
ions, H) across the inner This process creates a'proton gradient, also
space.
into the intermembrane force.
as the protord motive

electrons
6. Oxygn's Role:
electron acceptor in the ETC. It accepts
final
Oxygen (O) serves as the combines with protons to form.water (H,0).
oxygen
at Complex IV, where

7. ATP $ynthesis: the inner mitochondrial membrane is used

generated across Protons
The proton gradient through a process called chemiosmotic.coupling. ATP
called
to drive ATP synthesis
mitochondrial matrix through a protein complex
from adenosine
flow back intothe protons powers the synthesis of ATP
synthase, and this flow of phosphate (Pi).
diphosphate (ADP) and inorganic

8. Energy Production: substantial

transport chain is the production ofa
electron
The overall result of the primary energy currency of the cell.
is the
amount of ATP, which

2
 CompBex I
ComplexI, also known as NADH dehydrogenase or NADH: chain ubiquinone
(ETC)
oxidoreductase, is the first protein complex in the electron transport of multiple
is a.large protein complex consisting
of cellular respiration. Complex Ihydrophilic, mitochondrial
subunits, both hydrophobic and in the transfer and it spans thie,inner electrons from
membrane. It plays a vital role of high-energy ele
(nicotinamide adenine dinucleotide) to ubiquinone (coenzyme Q) while
NADH across.the inner mitochondrial:membrane.
pumping protons (hydrogen ions)

Here's how Complex I functions:

1. Electron Transfer: is
the
generated- earlier in acid
from NADH, which
Complex I accepts. electrons particularly during glycolysis.a
andthecitric
respiration,
process of cellulat
cycle (Krebs cyole).
+2H+ + 2e*
NADH + H+> NAD*
mononucleotide:(FMN) cofactors
2. Proton umping: gnsian,
within Complex I, it actively
As electrons afe: (Fe-S)-proteins and mitochondrial
fromthe
and a series of mitochondrial membrane gradient:or
across theinner creates á proton
processi
pumps protons intermembrane space. This
matrix into the
protonmotiveforce.
#2e> FMNH
FMN+ 2H
2Fe?+ ubiquinone (Q)
2Felt+ 2e g given to
electrohs arethen
These two
thè.complex per 2electrons
transported out of
Four H*
2Fe²gives 2e to 2Fe.isoxidfzed2Fe*
(ubiquinol)and
.

toQH;
Qis reduced

3
Complex II
known as succinate dehydrogenase, is the second protcin
Complex II, jalso
the electron transport chain (ETC) of cellular respiration. It plays a
complex in electrons from succinate, a molecule in
crucial role in transferring high-cncrgy
ubiquinone (cocnzyme Q), contributing to
the citric acid cycle (Krebs cycle), totriphosphate (ATP) in cells.
the overallgeneration of adenosine

Here's how Complex II functions:

1. Electron Transfer:
which accepts electrons from NADH, Complex II receives its
Unlike Complex I, produced during the citric acid cycle.
electrons from succinate, a molecule electrons are
in this process, and two
Succinate is converted to fumarate cofactor within Complex
(FAD)
transferred to the flavin adenine dinucleotide

Succinate FAD> Fumarate + FADH,

2. FADH, Formation:
electrons transferred to FAD within Complex II result in the formation of
The carrier molecule. FADH, then tries to
FADH), which is a high-energy electron
baçk into FAD by passing its electrons to 2Fe", which is reduced to 2Fe?*
oxidize
(Like in Complex 1)
2Fe' + 2e ; 2Fe?+
3. Ubjquinone Interaction: lipid-soluble
electrons from 2Fe?* arethen stolen by ubiquinone (Q), awhich
These inner mitochondrial membrane.
carries
carrier and can move within the
them to complex III.
0+2Fe2t ’ 2Fe'* +QH,
4. Proton Movement: mitochondrial
not actively pump protons across the inner
Complex II does eventually
However, the electrons it transfers to ubiquinone
Imembrane.
pumping by other complexes in theelectron transport chain.
particlpate in protcn
Complex II

Complex 1, also known as Q-cytochrome coxidoreduetase or cytochrome c

reductase, is thc third protcin complex in the clcctron transport chain (ETC) of
cellular respiration. Complex II is alarge protein complex comprising multiple
subunits, and it spans the inner mitochondrial membrane. It plays avital role in
transferring electrons from ubiquinol (reduced coenzyme ) to cytochrome c
while pumping protons (hydrogen ions) across -the :inner -mitochondrial
membrane.
Here's how Complex III functions:

1. Electron Transfer:
Complex IIfeceives electrons from ubiquinol (QH; or reduced coenzyme Q),
which carries two high-energy electrons. Complex III contains cytochrome
c1(contains óne heme group), cytochrome b(contains two heme groups b.
and b), and 2Fe-2S groups (Rieske center). Cytochrome ccan only accept a
single electron. QH, binds and releases two electrons, one electron moves to
Riske center then to the heme group of cytochrome cË causing Fe" to reduce to
Fe,Then tó oxidized cyt cwhich the diffuses away as reduced oyt eto complex
IV. The second electron moves cytochrome bË and bH heme groups-before being
picked up by an internal ubiquinone to recycle the electron into a semi
ubiquinoneradical ion (0)
Another QH, binds and releases two electrons, one electron moves to Riske
reduce to Fe*,
center then to the heme group of.cytochrome c causing Fe'* to
Then to oxidized cyt c which the diffuses away as reduced cyt cto complex IV.
being
The second;electron moves cytochrome bË and bH heme groups before form
the matrix to
picked up smi ubiquinone radical ion (Q),abstract. 2H* from
Ubiquinol (QH)) and moves out of the complex
2Q cycles. are involved
2QH;+2H2cytox ’ 4Hourt2cytedtQHs
Proton Pumping:
a series of iron-sulfur clusters and
As elagtpone move through Complex III via
protons are actively pumped across the
hemc groups(cyt CË and cyt bL and bu),
inner mitochondrial membrane from the mitochondrial matrix into the
proton gradient or proton
intermembrane space. This proton pumping creates a
motive force.

5
Complex IV
also known as cytochrome c oxidase, is the fourth and final protein
Complex IV,
cellular respiration. It plays a
complex in the electron transport chain (ETC) offrom cytochrome c to molecular
crucial role in transferring high-energy electrons
contributes tothe production of
Oxygen (O:), the final electron acceptor, and thus copper
a3) and 2
water (H,0). Cytochrome c oxidase utilizes 2 hemes (a and
sites. Here's how Complex IV functions:

1. Electron Transfer:
located
Complex IV receives electrons from cytochrome c, asmall soluble protein
Cytochrome c carries electrons that
in the intermembrane space of mitochondria.
have been transferred through the previous complexes of the ETC.
Cu2t +e5Cut
Fet +e5Fe?t
total of two electrons. One
Two reduced cytochrome c molecules give off a
electron stops at the Cus while the other stops at Heme. as, Once the Heme a3 and
1molecule can bind and abstract the
Cup are in their reduced form an O:
reduced cytochrome c molecule
electrons toform a peroxide brigde. Twomore obtained from the
are
two more electrons. 2H"
are oxidized to transfer additional
Cup-OH and Heme as -OH. The
matrix to break the peroxide bride to formthe matrix Oxidizes the Heme ag and
abstractionjof two more protons 2H* from
water molecules.
Cup into their originalstate and release two
+4Hout+2H,0
4cyt Credt8H"int4e+O2 -’ 4 cyt c oxi
+2H"outHzO
2cyt c redt4Hint2e+1/202 ’2 cyt c oxi

2. Oxygen Reduction:
oxygen (0:) by accepting
Complex IVfacilitates the reduction of molecular electron acceptor in the
the final
electrons from cytochrome c. Oxygen serves as
electron transport chain.
3. Water Formation:
cytochrome c to oxygen within Complex IV,
ssAS electrons are transferred from
water (Hz0). This process involves the
molecular. oxygen is reduced to form wnter nolccules,
release of
binding of cxygen atom and the
O2 (e) t 4H* + 4e*> 2H,0 ()
6
 4. Proton Movement:
(hydrogen ions, H) arc activcly pumped across the inner mitochondrial
Protons intermembrane space as
membrane from the mitochondrial matrix into the a proton
proton pumping crcates
electrons move through Complex IV. This mitochondrial membrane.
the inner
gradicnt, or proton motive forcc, across

Intermembrane 2H'
$pace (P side) 4H*
AH

+0,+ 2H* H,0

Succinate Fumarate
NADH +H+ NAD
Matrix (N side)

electrons and protons:through the.four,complexes

Fig 2: Summary of the flow of
of the respiratory chain.

Energetics of oxidative phosphorylation

from redox pair NAD*NADH (E, - 0.32) to finally
The transport of electrons =+0.82) may be simplified and represented in the
(E,
the redox pair ½ 02/H,0
following equation NAD
H,0 +
1/20,+ NADH + H* ’
oxidation- reduction
relationship between the energy changes in
The direct the equation
reactions and AG° is expressed by
AGO' =-nFAEO! constant (23
number of electrons transferred and F is Faraday's two redox
where n is the difference between these
kcal/mole volt). The redox potential redox pairs is (AE°)1.14 V, which is
these two
potential difference between
equivalent to an energy
AE°=-2x23(1.14) =-52.5Kcal/mol. equals
synthesized in the ETC when NADHis oxidized which
About 2.5 ATP are
calculatcd
of energy conservation is
to -18.2s Kcal/mol
Kcal/mol). The cfficiency
(each ATP= -7.3
as
18.25x100/52 =35%
7
 of energy is trapped in the form
oxidized, about 35% liberationisnot a
wasteful
Thereforc, when NAIDH is heat. The heat
remaining is lost ascontinuously to generate ATP.Further, this
of 2.5 ATP and the
ETC to go on
process/ since it allows
maintain body temperature,
heat is necessary to

synthesis approximately
Encrgetics ofATP of NADH by O2 is
oxidation so
overallfree energy release from approximately -47.9 kcal. This 4G° is
The FAD(2H), it is oxygen fromH,0.
-52.5 kcal, and from we never synthesize
never reversible; formation from the
pathways
negative that the chain is and FAD(2H)
is so negatíve that it drives NADH and glycolysis,to completion.
It such as the TCA cycle
of fucloxidation, NAD, = 10*
NADH + H* ’ H0 +
1/20;+
H,0 + FAD 6+ of 2 of:
1/2O2+ FADH; ’ equivalent.tothereduction
NADH donates two
electrons,
accepted estimate ofthe
Overall, each
A generally (but not universally)
protons:(4H)
complex
are pumped'at protons
an O2 molecule.
synthesis is that four complex IV With four formed
stoichionetry ofATP two at
at complex III, and estimated (10/4) 2.5ATPs
are
I, four protons cach ATP synthesized, an
each of the:other FAD(2H)
translocated for 1.5 ATPs for has
N¬DH Oxidized and (6/4)electrons Co
O.Nevertheless,the ratio
for each to
that donate
containing flavoproteins
difficult to determine.
remained extremely are synthesized when one
indicated that 3 ATP synthesized
Traditiona! calculations ratio -3). Similarly, 2 ATP are
oxidized(P: O
molecule of NADH is
FADH, isoxidized (P: Oratio =2).
when one molecule
of
Electron Shuttle Systems mitochondrial
transport is produced in the
NADH used in electron NADHis on:the matrixX: sideofthe inner
the
Most of
site ofComplex I
for impermeable to NAD+ and
matrix. The binding mitochondrial membrane is reoxidized into NAD+ to
membrane. The inner of cells needs to by
NADH. NADH
formed in the cytosol conditions, NAD+ isregenerated need to
anaerobic electrons of NADH
glycolysis going. Under conditions, the
keep dehydrogenase. Under aerobic
lactate mitochondria.
into the matrix of the
be shuttled

8
 The Glycerophosphate Shnttle
NADH, H' NAD

glycewi 3-plo0l:al
hydtoSnAN
CHSOH
tHPO,2 H,OPO,*
Dihydroxyncetane Glycorol
phosplato 3-plrosphàta
Mitociondisl
lyaof 3-plhosphate
Cytosol dellydrogunas
E-FADHz. E-FAD

Matrix

Fig 3: Glycerophosphate shuttle

This shuttle system uses two distinct glycerol 3- phosphate dehydrogenases. The
of
first is found in the cytoplasm, the other is found.on, the intermembrane side,
the inner mitochondrial membrane.
transfers its electrons to
In the first step, NADH produced in the cytosol-
dihydroxyacetone phosphate to form. glycerol-3-phosphate. Glycerol-3
porin. Glycerol-3
phosphate enters the inter mitochondrial space through a
phosphate js then reoxidized into dihydroxyacetone phosphate by an FAD
dependent mitochondrial membrane glycerol3-phosphate dehydrogenase. In this
The two
shuttle the electrons ofNADH are transferred to FAD to form FADH2.
forming
electrons bound by the ADH2, áre transferred directly to .coenzyme Q
result ofthis shutle is 1.5
QH2. QH2 carries the electrons to complex II. The
ATP/NADH.
Ihe Malate-Aspartate Shuttle.

NADH + H NADT
Malate
Oxaloacetate
Aspartate
a-Ketoglutarate Glutamale

Cytosol

d:Ketoglutarate Glutamate
Matrix Malate
Oxaloacetate
Aspartate
.NAOH+ H NAD

shuttle
Fig 4:Malate-Aspartate malate dehydrogenase which
oxaloacetate is reduced to malate by.
In the cytosol, transported across the inner mitochondrial
reductant.Malate is Nowin the
uses NADH as the dicarboxylic acid or tricarboxylic acid carrier.
to generate
membrane biv the reoxidized by malate dehydrogenase Complex I. The
matrix, the malate is which can now transfer its electrons to a-ketoglutarate.
Oxaloacetatejand NADH and
glutamineto form aspartate membrane by the
oxaloacetatejis transaminated by mitochondrial
transported across the inner transaminates a-ketoglutarateto
Aspartate,can be cytosol aspartate
dicarboxylig acid carrier. In the
completingthe cyc<e.
reform oxaloacetate ATPNADH and is completely
reversible.
generates 2.5
This shuttlejsystem
Oxidative phosphorylation for, this
Peter Mitchell, isthe.paradigm
inherentin the
chemiosmotic model, proposed by electrochemicalenergy inner
The According to the model,the separation of charge across the ATP
mechanism. of
in proton
concentration and
proton-motive force-drives the synthesis
associated
difference membrane--the
mitochondrial matrix through a proton pore force, the
the
passively back into crucial role ofthe proton
motive
flow
as protonssynthase. To emphasize this
with ATP sometimes
synthesis is
equation for ATP
written
ATP +H,0++ nHin
ADP + Pi+ nHtout’

10
 4H+

:Intetinombrine.
spaco

Puinnarato o21
Succluate
NADH + H* NAD
ADP +Ri
Mat1ix
ATP

poteiittal Oentth
pH nstde
.lkailnc

Fig: 5 Chemiosmotic model chemiosmotic theory applied to.mitochondria,

In this simple representation of the oxidizable substrates pass througb a chain of
electrons from!NADH and other inner membrane. Electron flow is
asymmetrically in the chemical
carriers arranged the membrane, producing both a
accompanied by proton transfer across
electrical gradient (AY). The inner mitochondrial
gradient (ApH) and an' matrix onlythrough
impermeable to protons; protons can reenter the drives:protons back
membrane is The proton-motive force that
proton-specific channels (Fo). synthesis,catalyzed by the Fi
the energy for ATP chemiosmotic
into the matrix provides
with Fo. Mitchell"was
ridiculed; but the:
complex assooiated
Nobel prize.
hypothesis eventually won him a
Htin+Htout
AG = RT In
fH +out +FAY
H+in] V1mol-1)
F=Faraday'sconstant (96,485 J membrane
difference across the 180 AG:at
my, 37°C =23.3 kJ/mol
AY= potential
acidic outside),AY =
Typically, ap} = 1(more
ATP synthase fifth and finalproteincomplex in
ATP synthase, is the Unlike the previous
Complex V, also known as cellular respiration. responsible
transport chain (ETC) of electron transfer but is
the electron: V
in
does not participate (ATP), the cell's primary
energy
Complex
complexes,
synthesis of adenosine triphosphate
for the
how Complex V functions:
Here's
consists of two main
currency.
and
1. Proton Flow: mitochondrialmembrane inner
mitochondrial
the inner the
Complex V spans itis embedded and spans
unit,
'oh'
components: The F,
11
 (hydrogen ions, l1+) flow back into the mitochondrial matrix
nemnbranc. Protons
Fo, driven by the proton gradient crcated by the previous complexes
through polypeptide chains and is connected to Fl.
(Complexes I, III, and IV). F, has 4
headpiece, it projects into the mitochondrial matrix, it catalyzcs ATP
The F B3,1y, 16, 1[). The alpha chains
synthesis. Funit has 9 polypeptide chains (3a,chains have catalytic sites for ATP.
beta
have binding sites for ATP and ADP while
ATP synthesis requires Mg**
2. ATP Synthesis:
component of Complex V, they cause a rotor-like
As protons flow through theF, mitochondrial membrane. This -rotary.motion is
structüre to irotate within the
catalytic sitesfor ATP synthesis.
transmitted to the FË headpiece, which contains functional unit:
alpha-beta
The F1 has 3 conformation states for the
O state Does not bind.substrate or products
state - Loose binding of substrate and products
T state-- Tight binding of substrate and products
3. ATP Production:
conformational changes in its catalytic
The rotation of the Fi headpiece induces
inorganic phosphate (Pi) to
sites, allowing adenosine diphosphate (ADP) andsynthesizes approximately three
combine and form ATP. Each rotaion ofthe rotor
ATP molecules.
chemically identical but conformational distinct functional states. "O"
F has 3
open conformation with no affinity for substrates and is catalytically
means
catalytically sluggish. "T" binds ligands
inactive. "L" binds ligands loosely and and Pi binds to "L" site. Then energy
tightly and catalytically active. l= ADP conformation
dependent conformational change occurs. 2= ATP is synthesized;
teleased with confirmation: change, 4= old
is again changed. 3= ATP is'continues
confirmation regained and cycle
ADP t D
,ADH Pp 44 ATP

Proton inllux ADP + pi

ATP
Energy (4
(1) (2) (3
synthase.
Fig 6: The binding change mechanism for ATP

12
 F
Headpiece

FPore

H*
Cyoplasmic slde

Fig 7: ATP synthase (FoF1ATP ase)

ATP-ADP Translocase
ATP must be transported out of the mitochondria
ATP out ADP in through a translocase
ATP movement out is favored because the cytosol is "+" relative to
the "-" matrix

ATP out and ADP in is net movement of a negative charge out -

cquivalent to a H* going in
So every ATP transported out costs one H
One ATP synthesis costs about 3 H
Thus, making and exporting 1ATP = 4H*
Uncouplers
Chemical uncouplers
oxidative phosphorylation depends
The coupling between electron transport and membrane to H translocation.
mitochondrial
on the impermeability of the inner intermembrane space to the matrix is
the
The only way for protons to go from
13
 uncouple electron transport from oxidative
Uncouplcrs protons
through ATP synthase.collapse the chemiosmoticgradient by dissipating
phosphorylation. They
inner mitochondrial membranc.
across the p-trifluorocarbonyl-cyanide
carbonyl cyanide making them
2,4-Dinitrophenol, dicumarol and have hydrophobic, character have.dissociable
methoxypheny| hydrazone (FCCP) all these. decouplers also
inembranc. All of intermembrane space to the
soluble in the bilipid from the
to carry protons
protons allowing them pH gradient.
the
matrix which collapses
the proton gradient is lost as, heat.
of
The potential energy

ØH IotenemrA spece, Low pi

bnevilocbopdnialSterbnne
Dieupuro!

Diruocpharol

..

tboxyphesol bydrozoae
Carbonyl cyide.p-aiuorone
-FCCP

uncouplers
Fig 8: Chemjcal
Organisms.toGenerateHeat.
Enable transport generates
Endogenous Uncouplers from electron
uncoupling of oxidative phosphorylation
animals (including human beings)
The animals and newborn
tissueis to the high
brown dåe thermogenin
heat. Hibernating adipose
brown,adipose tissue. The endogenousproteincalled
contain tissue. An apassiveproton
mitohondria content of the transport by.opening up the
from electron The collapseof
uncouplesATPsynthesis the inner mitochondrial membrane.uncoupler.
through also anendogenous
channel (¯CP-1) heat. Thyroxine is
generates
pH gradient
transport chain complex I
Inhibitors of electron All three of these
barbiturates, Demorol.
Complex I:
Rotenone, Fe-S clusters ofcomplex I.
oxidation of the
inhibitorsblock the

14
 specifically block clectron
2-Thenoyltrifluor0acctonc and carboxin
Complex 11: transter in
antibiotic that inhibits clectron
is an cocnzyme
Complcx I: Antimycin A,transfer of clcctrons betwcen Cyt by and
complex IIIby blocking the half Qcycle.
during
Qbound in the complex monoxide all inhibit clectron
transport
azide and carbon the iron
Complex IV: Cyanide,
inhibit clectron transfcr by binding tightly withwhen the
all iron
in Complex IV. Theyas or heme a,. Axide and cyanide bind,to.the when it is in
coordinatcd in Cyt binds to the iron
in the ferric state (Fe), Carbon Monoxide inhibitors at this site which
iron is (Fe).Cyanide and azide are potcnt
the ferrous'state toxicity.
accounts for their acute
Inhibitorsof ATP Synthase
DCCD, forms covalent bonds to a glutamate residue
Diclyclohexylçarbodiimide attached it blocks the proton
When DCCD is covalently
of the cisubunit ofFo. rotation and ATP synthesis tocease.
channel, which causes the and blocks the flow of
ATP synthase F, subunit
Oligomycin binds directly to
protonsithrough the channel.

Regulation of ATP synthesis energy.homeostasis.

synthesis is çritical
a aspect of cellular and avoid
The regulation of ATP productiontomeet energy demands eficientlyoxidative
Cells need toadjust ATP synthesis primarily"occurs through
wasting resources. ATP involves the activity'of ATP synthase,
and it
phosphorylation in the mitochondria, for ATP generation. Here are some key
responsible.
which :is the enzyme ATP synthesis:
regulatory mechanisms of
The driving forcefor ATP synthesis
(Proton Motive Force): (ApH and A)created across the
1. Proton Gradient proton motive force
proton gradient or electron: transport chain (ETC). The
is the membrane during the through ATP synthase
inner mitochondrial back intothe mitochondrial matrix proportional to the
flow of protons (H") rate of ATP synthesis is directly
The
powers ATP synthesis.
proton motive force.
to adenosine
and the ratio of ATP
levels and
2. ATP/ADP
Ratio: Cellular ATP
synthesis. When ATP levels are high ATP
regulate ATP regulator of
diphosphate (ADP) can as a negative
allosteric
demands are met, ATP acts
energy
15
 Conversely, when ATP levels drop and ADP
sunthase, inhibiting its activity. demands, ATP synthase is activated to produce
levels rise due to increased
energy
moreATP

is essential for cfficient ATP

Adequate oxygen supply
3. Oxygen Availability: phosphorylation. Oxygen:serves'as the finalelectron
synthesis through oxidative the absence of oxygen
chain (ETC). Ii
(hypoxia
acceptor in the electron transport
impaired, and ATP synthesis is
reduced.
becomes
or anoxia), the ETC

the mitochondrial matrix can influence ATP

pH of ATP synthase,
4 pi Regulation: The (acidic conditions)cantinhibit
in pH pH
synthase activity, A decrease
(alkaline conditions) can stimulate its:activity.
while an -increase. in pH and transport across tlhe
result from factors like proton accumulation
changes can
inner mitochondrial membrane.

metabolic.reactions, including
Temperature affects the rate of
increase the
5. Temperature: synthesis. Generally, higher tempratures can
those involved in ATP lower temperatures
can:decrease. it..
synthesis, while
rate of ATP

availability of. metabolic. substrates, such as

6. Nutrient;
Availability: The
the rate of ATP synthesis. Different substrates
impact efficiency and
glucose and fatty acids, can chain at variouspoints, influencing its
enter the electron transport
the rate of ptoton pumping.
like thyroidhormones can influence
Hormones
7. Hormonal
Regulation:
synthesis by affecting.the, number and efficiency
ATP
mitochondrialactivity and
of mitochondria in cells.
mitochondrial
Uncoupling proteins (UCPs) in the inner
are
8. Uncoupling
Proteins:
proton gradient and reduce ATP synthesis. They and
membrane can dissipate the can be regulated by factors 1like fatty
acids
involved in thermogenesis and
hormones.

16
 oxygen
production of reactivedamaging
Spccies (ROS): Excessive ATP synthesis.by defense
Oxygen
9. Reactive within mitochondriachain can disrupt synthase. Cells have.
and ATP
species (ROS) electron transport to mitigate ROS
effects.
components of the antioxidant enzymes,
mechanisms,including
to ensure that cells
controlled environmental
ofATP synthesis is tightly demands and
regulation energy maintain.cellular energy
Overall, the efficiently in response to
procuce ATP mechanisms help needed.
These regulatory production'when it is not
conditions. ATP
prevent wasteful
homcostasis and

17