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17 TCA Cycle and Biological

Oxidation
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Topics Included
• TCA Cycle (Citric Acid Cycle/ Krebs Cycle) • High Energy Compounds
• Shuttle Mechanisms • Electron Transport Chain
• Inhibitors of Electron Transport System • Inhibitors of Electron Transport Chain
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TCA CYCLE (CITRIC ACID Steps of TCA Cycle

CYCLE/KREBS CYCLE)
Definition
• Sequence of reactions in mitochondria that oxidizes
the acetyl moiety of acetyl-CoA and reduces
coenzymes, that are reoxidized through the electron
transport chain, linked to the formation of ATP
• The citric acid cycle is the final common pathwayQ
for the oxidation of carbohydrate, lipid, and protein
• Site: Mitochondria.
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Citrate Synthase
• Acetyl CoA + Oxaloacetate ----> Citrate
• First Tricarboxylic Acid formed is Citrate (6C)
• Irreversible StepQ (AIIMS June 2000)
• Citrate can cross the mitochondrial membrane and
release Acetyl CoA for the synthesis of Fatty Acid by
ATP Citrate Lyase.
Aconitase (Aconitate Hydratase)
• Citrate isomerized to Isocitrate

• Reversible reaction
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Overview of TCA Cycle

• The reaction occurs in two steps: dehydration to cis-
aconitate and rehydration to isocitrate
• Inhibited noncompetitively by FluoroacetateQ
• Aconitase is a Lyase.

Isocitrate Dehydrogenase
• Isocitrate undergoes dehydrogenation catalyzed
by isocitrate dehydrogenase to form, initially,
oxalosuccinate
• Oxalosuccinate is decarboxylation to α –ketoglutarate
(5C)
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• The decarboxylation requires Mg2+ or Mn2+ ions

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• First Oxidative decarboxylation

• 1 NADH is formed
Fig. 17.1: Overview of citric acid cycle • Reversible reaction.
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αKetoglutarate Dehydrogenase 5 Coenzymes of this enzyme are

• αKetoGlutarate (5C) oxidised and decarboxylated to 1. Lipomide
Succinyl CoA (4C) 2. Thiamine Pyrophosphate
• Second Oxidative Decarboxylatio 3. NAD+
• 1 NADH is formed 4. FAD
• Physiologically Unidirectional step 5. Coenzyme A
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• Multienzyme Complex similar to Pyruvate • Alpha KetoGlutarate Dehydrogenase noncompeti-

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Dehydrogenase tively inhibited by ArseniteQ.

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Fig. 17.2: TCA cycle

Succinate ThiokinaseQ (Succinyl-CoA Synthetase) Succinate Dehydrogenase

• Convert Succinyl CoA to SuccinateQ • Succinate undergo dehydrogenation reaction,
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• 1 ATP/GTP is generated forming fumarate

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• GTP is generated in Gluconeogenic tissues like Liver • The enzyme contains FAD and iron–sulfur (Fe:S) protein
and Kidney • The enzyme directly reduces ubiquinone in the
• Substrate Level Phosphorylation. electron transport chain
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TCA Cycle and Biological Oxidation   | 401

• Only enzyme in TCA cycle attached to Inner Concept of regulation of TCA cycle
mitochondrial Membrane • High energy states inhibit TCA Cycle and vice versa
• All other enzymes are in the mitochondrial matrix • High ATP/ADP ratio and High NADH/NAD+ ratio are inhibitors of
TCA Cycle.
• FADH2 is formed
• High ADP and High NAD+ are activators of TCA Cycle
• Succinate Dehydrogenase is competitively inhibited • Products of the pathway inhibit the regulatory enzymes
by Malonate.Q
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Fumarase (Fumaratehydratase) Allosteric activators and inhibitors of individual

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enzymes
• Catalyzes the addition of water across the double
bond of fumarate, yielding malate • Long Chain Acyl CoA and ATP inhibit Citrate
• Fumarase is a Lyase. Synthase
• Isocitrate Dehydrogenase is inhibited by ATP and
Malate Dehydrogenase NADH
• Final step in TCA Cycle • Succinate Dehydrogenase is inhibited by Oxaloacetate
• Malate is converted to Oxaloacetate • In Muscle, the dehydrogenases of TCA Cycle are
• Oxalo acetate is regenerated activated by Ca2+, which increases during muscle
• 1 NADH generated contraction
• Oxaloacetate regenerated, hence Oxaloacetate has a • Mitochondrial Isocitrate Dehydrogenase is activated
catalytic role like Ornithine in Urea Cycle. by ADP
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Inhibitors of TCA CycleQ • In a tissue such as brain, which is largely dependent

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• Aconitase noncompetitively inhibited by Flouroac- on carbohydrate to supply acetyl-CoA, control

etateQ of the citric acid cycle may occur at pyruvate
• Alpha Ketoglutarate Dehydrogenase noncompeti- dehydrogenase.
tively inhibited by ArseniteQ Remember
• Succinate Dehydrogenase is competitively inhibited To answer whether a compound is an activator or inhibitor of an
by Malonate.Q (Inhibitor of complex II of ETC). enzyme, think whether they are substrate or products of that enzyme/
pathway
Energetics of TCA CycleQ
TCA Cycle is truly an Amphibolic PathwayQ
Method of ATP No of ATP A pathway with both catabolic and anabolic role is called amphibolic
Reaction Production Generated pathway.
Isocitrate Dehydrogenase 1 NADH enter ETC 2.5 ATPs Anabolic Role of TCA Cycle
α KetoGlutarate Dehydro- 1 NADH enter ETC 2.5 ATPs • Citrate to Fatty Acid Synthesis
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genase • Alphaketoglutarate to GABA & Glutamate

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Succinate Thiokinase Substrate level Phos- 1 ATP • Succinyl CoA to Heme

phorylation • Oxaloacetate to Gluconeogenesis
Succinate Dehydrogenase 1 FADH2 enter ETC 1.5 ATPs Catabolic role of TCA cycle
Malate Dehydrogenase 1 NADH enter ETC 2.5 ATPs • Acetyl CoA is completely oxidized to CO2.
Total number of ATP per turn 10 ATPs
of TCA Cycle Anaplerotic Reactions of TCA CycleQ
The 6 Carbon, 5 Carbon and 4 Carbon intermediates are used for
Three molecules of NADH Q and one of FADH2 are various synthetic or anabolic reactions mentioned above. So these
produced for each molecule of acetyl-CoA catabolized intermediates get depleted.
To replenish these compounds filling reactions takes place. These
in one turn of the cycle.
filling up reactions are called Anaplerotic reactions.
Regulation of TCA Cycle Filling up (Anaplerotic) Reactions are at the level of Oxaloac-
etate (6C)
Regulatory steps are • Hydroxy Proline, Serine, Cysteine, Threonine, Glycine to Pyruvate
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• Citrate Synthase • Lactate to Pyruvate

• Isocitrate Dehydrogenase
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• Tryptophan to Alanine to Pyruvate

• α Ketoglutarate Dehydrogenase • Pyruvate to Oxaloacetate by Pyruvate CarboxylaseQ, is a major
filling up reaction
• Pyruvate dehydrogenase is also considered as the
regulatory step of TCA Cycle. Contd...
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Contd... Glycerophosphate Shuttle

Remember This shuttle is present in some tissues (e.g., brain, white
• Acetyl CoA is a positive Allosteric effector of Pyruvate muscle), but absent in heart tissue.
Carboxylase
The number of ATPs from 1 NADH transported to mitochondria
At the level of Alpha Ketoglutarate (5C)
by Glycerophosphate Shuttle
• Glutamine and Glutamate are the major anaplerotic substrates of
Since the mitochondrial Glycerophosphate Dehydrogenase is linked
Alpha Ketoglutarate
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to the respiratory chain via a flavoprotein (FAD) rather than NAD, only
At the level of Succinyl CoA (4C) 1.5 mol rather than 2.5 mol of ATP are formed per atom of oxygen
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• Valine, Isoleucine and Methionine consumed.

• Compounds that form Propionyl CoA
At the level of Fumarate (4C)
• Tyrosine and Phenyl Alanine.
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Fig. 17.4: Glycerophosphate shuttle

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Malate Shuttle
Malate shuttle system is of more universal utility. Used
to transport NADH from Cytosol to Mitochondria.

Reactions involved in Malate Shuttle

• NADH converted to NAD+, Oxaloacetate to Malate
• Malate enter mitochondria via α Ketoglutarate
Transporter
• Malate converted to Oxaloacetate, NADH is released
• But there is no transporter for Oxaloacetate
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• Oxaloacetate react with glutamate to form aspartate

and (α-ketoglutarate by Transamination)
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Fig. 17.3: Anaplerotic reactions of TCA Cycle

• Aspartate and α Ketoglutarate is transported to
Vitamins in TCA Cycle cytosol and Oxaloacetate is reconstituted.
• Pantothenic Acid as a part of CoA
• Riboflavin as FAD
• Thiamin
• Niacin as NAD+

SHUTTLE SYSTEMS
• NADH cannot penetrate the mitochondrial
membrane, but it is produced continuously in the
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cytosol by 3-phosphoglyceraldehyde dehydrogenase,

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an enzyme in the glycolysis sequence

• The transfer of reducing equivalents is carried out by
using the various shuttle systems Fig. 17.5: Malate shuttle
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TCA Cycle and Biological Oxidation   | 403

Creatine Phosphate Shuttle • CKm (An isoenzyme of creatine kinase (CKm) is

• Facilitates Transport of High-Energy Phosphate (e.g. found in the mitochondrial intermembrane space)
ATP) from Mitochondria transfer high-energy phosphate from ATP to creatine
• Sites are heart and skeletal muscle. form Creatine Phosphate
• The creatine phosphate is transported into the cytosol
Reactions of Creatine Phosphate Shuttle via protein pores in the outer mitochondrial mem-
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• ATP emerging from the adenine nucleotide trans- brane, Creatine Kinase generate extramitochondrial
porter to intermembrane space ATP.
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Fig. 17.6: Creatine phosphate shuttle

Redox Potential of Common Redox Couples Contd...

Electrons are transferred in the ascending order of redox Redox couple Redox potential
couple. Fumarate/Succinate +0.03
Redox couple Redox potential Cyt b; Fe3+/Fe2+ +0.08
H+/H2 -0.42 Ubiquinone(CoQ) +0.10
NAD+/NADH -0.32 Cyt c1; Fe3+/Fe2+ +0.22
Lipoate -0.29 Cyt a; Fe3+/Fe2+ +0.29
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Acetoacetate/β Hydroxybutyrate -0.27 Oxygen/water +0.82

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Pyruvate/Lactate -0.19
Remember this table is important for national board
Oxaloacetate/Malate -0.19
pattern of exams. It is important to learn the order in
Contd... which they are arranged, not the value of redox potential.
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Self Assessment and Review of Biochemistry

ELECTRON TRANSPORT CHAIN

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Fig. 17.7: Flow of electrons in ETC

Components of Electron Transport Chain ‒ 2H+ pumped to Intermembrane Space

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Site: In the Inner Mitochondrial Membrane ‒ The final electron acceptor of ETC is oxygen.
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Components of the Electron Transport Chain Q are

contained in four large protein complexes Mobile Complexes in the
• Complex I NADH Coenzyme Q Oxidoredutase
Electron Transport Chain
‒ Contain FMN and Fe-S (Iron- Sulfur) Complex Coenzyme Q
‒ Pumps 4 H+Q to Intermembrane Space (PGI Nov • Also called Ubiquinone
09 May 10) • Quinone derivative with a polyisoprenoid side chain
• Complex II Succinate Q Reductase • Lipid solubility and small size make it a mobile
‒ Contain FAD and FeS Complex electron carrier.
‒ No H+ pumped to Intermembrane Space
• Complex III Q Cytochrome c Oxidoreductase Cytochrome C
‒ Contain Cyt b and Cyt c1 • Mobile electron carrier between Complex III and
Complex IV
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‒ Contain Fe-S Complex

• Also play a role in programmed cell death.
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OXIDATIVE PHOSPHORYLATION
The flow of electrons through the respiratory chain
generates ATP by the process of oxidative phosphorylation.
Oxidation coupled with Phosphorylation.
The theory behind the oxidative Phosphorylation is the
Chemiosmotic theory.

The Chemiosmotic TheoryQ

• Proposed by Peter Mitchell in 1961
• Postulates that the two processes, oxidation and
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Fig. 17.8: Components of electron transport chain

Phosphorylation are coupled by a proton gradient
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Q
Pumps 4 H+ to Intermembrane Space (PGI Nov 09 May 10)
• Complex IV Cytochrome c Oxidase
‒ Contain Cyt a and a3 (now known as Heme a a3)
and Copper A and Copper B centre
across the inner mitochondrial membrane
• The proton motive forceQ caused by the electrochemi-
cal potential difference (negative on the matrix side)
drives the mechanism of ATP synthesis.
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TCA Cycle and Biological Oxidation   | 405

COMPLEX V–ATP SYNTHASE COMPLEX

• Also called as the Fifth Complex of Electron transport
Chain
• The smallest molecular motor present in the human
body
• Location-ATP synthase is embedded in the inner
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mitochondrial membrane.
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Divided into two Subcomplexes

• F0 Subcomplex
• F1 Subcomplex.
F0 Subcomplex
• Hydrophobic in nature
• F0 spans the inner mitochondrial membrane
• Forms a proton channel
• Made up of a disk of 10 ‘C’ protein subunits. Fig. 17.9: ATP synthase
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Fig. 17.10: Inhibitors of ETC

F1 Subcomplex ATP Synthase Complex as a rotor-stator molecular

• Hydrophilic in nature motor
• Projects into the mitochondrial matrix • Because it has two functional unit.
• F1 is attached to F0 Subcomplex A rotating subunit
• Made up 9 Subunits (α3β3γδε) • Consist of F0 Complex and γ Subunit of F1 Complex
• γ subunit in the form of a ‘bent axle.’ A stationary subunit
• γ subunit is surrounded by 3α and 3β subunit
• F1 Complex other than γ subunit.
alternatively
• The flow of protons through F0 causes, rotation of F0
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Complex along with γ subunit of F1 complex to rotate Binding Change Mechanism

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• This causes the production of ATP in the F1 • The theory behind the ATP production in the β
complex subunit of F1 Subcomplex
• β subunit of F1 Complex is called Catalytic Subunit. • Proposed by Paul Boyer
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Self Assessment and Review of Biochemistry

• States that re-entry of protons through F0 Subcomplex • Dinitrocresol

causes rotation of γ subunit which in turn causes • FCCP [Fluoro Carbonyl Cyanide Phenyl hydrazine]
conformational changes in the β subunits of F1 • ? Aspirin in high dose.
Subcomplex.
Physiological Uncoupler
INHIBITORS OF ELECTRON • Thermogenin [Uncoupling Protein 1] in Brown
TRANSPORT CHAIN Adipose Tissue
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• Thyroxine
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Divided into • Long Chain Free Fatty Acid

• Inhibitors of Electron transfer
• ? Unconjugated Bilirubin.
• Inhibitors of Oxidative Phosphorylation
• Uncouplers of Oxidative Phosphorylation Ionophores
• Ionophores
• Ionophores permit specificcations to penetrate
membranes
Inhibitors of Electron Transfer
• Dissipate Proton Gradient
Between NADH and CoQ [At Complex I]
• Valinomycin
• An insecticide and a fish Poison Rotenone
• Gramicidin
• Amobarbital which is a barbiturate
• Nigercin.
• Piericidin A.
P:O Ratio
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Inhibitor of Complex II
• Represents the number of ATP molecules produced
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• TTFA (Tri enoyl TriFluoroAcetone) a Fe2+ Chelating in terms of reducing equivalents oxidized
agent
• No of inorganic Phosphates utilized for ATP
• Carboxin production for every atom of oxygen consumed
• Malonate, a competitive inhibitor of Succinate • For NADH - 2.5
Dehydrogenase.
• For FADH2 -1.5.
Between Cyt b and Cyt c [At Complex III]
High Energy CompoundsQ
• Antimycin A
• Compounds which yield energy of atleast 7 kcal/m
• British Antilevisite [Dimercaprol]
on hydrolysis
Inhibitor at Cytochrome c Oxidase [Complex IV] • Compounds whose free energy of hydrolysis more
• CO than that of ATP is called High energy phosphates
• Cyanide • Compounds whose free energy of hydrolysis less
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• H2S than that of ATP is called low energy phosphates.

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• Sodium Azide. Classification of High energy Phosphates

• Pyrophosphate, e.g. ATP
Inhibitors of Oxidative Phosphorylation
• Acyl Phosphate, e.g. 1,3 Bisphosphoglycerate
Atractyloside • EnolPhosphate, e.g. Phosphoenolpyruvate
By inhibiting the transporter of ADP into and ATP out of • Thioester, e.g. Acetyl CoA, Succinyl CoA
the mitochondrion. • Phosphagen, e.g. Phosphocreatine, Phosphoarginine.
Remember
Oligomycin an Antibiotic
• All high energy compounds given yield energy higher than ATP.
Completely blocksQ oxidation and phosphorylation. • Most of the compound contain Phosphate group (hence also called
By blocking the flow of protons through F0 Complex of High Energy Phosphates) except Acetyl CoA.
ATP Synthase.
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Free Energy kJ/ Free Energy

Uncoupler of Oxidative Phosphorylation High Energy Compound mol Kcal/mol
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Mechanism of Action—Disruption of Proton Gradient Phosphoenolpyruvate -61.9 -14.8

across the inner mitochondrial membrane Carbamoyl phosphate -51.4 -12.3
• 2,4 Dinitrophenol Contd...
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TCA Cycle and Biological Oxidation   | 407

Contd... Respiratory QuotientQ

Free Energy kJ/ Free Energy Measurement of the ratio of the volume of carbon dioxide
High Energy Compound mol Kcal/mol produced: volume of oxygen consumed in the oxidation
1,3-Bisphosphoglycerate -49.3 -11.8 of metabolic fuels.
(to 3-phosphoglycerate)
RQ (CO2
Creatine phosphate -43.1 -10.3 Energy Produced/
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ATP→AMP + PPi -32.2 -7.7 Yield O2 Con- Energy

Metabolic fuel (kJ/g) sumed (kJ)/L O2
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ATP → ADP + Pi -30.5 -7.3

Carbohydrate 16 1.00 20
Glucose-1-phosphate -20.9 -5.0
PPi -19.2 -4.6 Protein 17 0.81 20
Fructose-6-phosphate -15.9 -3.8 Fat 37 0.71 20
Glucose-6-phosphate -13.8 -3.3
Alcohol 29 0.66 20
Glycerol-3-phosphate -9.2 -2.2

REVIEW QUESTIONS
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TCA Cycle a. Malonate

b. Arsenite
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1. Which of the following is not an intermediate of

c. Fluoroacetate
TCA Cycle? (AIIMS 2014 May)
a. Acetyl CoA d. Fumarate
b. Citrate Ans. c. Fluoroacetate. (Ref: Harper 30/e p161-167)
c. Succinyl CoA • The poison fluoroacetate is found in some of plants,
d. Alpha Ketoglutarate and their consumption can be fatal to grazing animals
Ans. a. Acetyl CoA. (Ref: Harper 30/e p161-167) • Some fluorinated compounds used as anticancer
agents and industrial chemicals (including pesticides)
Acetyl CoA and Oxaloacetate are the starting materials
are metabolized to fluoroacetate
of TCA Cycle
• It is toxic because fluoroacetyl-CoA condenses with
2. Which of the following is true about Krebs Cycle? oxaloacetate to form fluorocitrate, which inhibits
(JIPMER May 2015) aconitase, causing citrate to accumulate.
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a. Pyruvate condenses with Oxaloacetate to form

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Citrate 4. First substrate of Krebs cycle is:

(AIIMS May 2007)
b. Alpha ketoglutarate is a five Carbon compound
a. Pyruvate
c. Oxidative Phosphorylation occurs in the cyto-
b. Glycine
plasm only
d. Krebs cycle can operate in anaerobic condition c. HCI
Ans. b. Alpha ketoglutarate is a five Carbon compound. d. Lipoprotein
Ref: Harper 30/e p161-167 Ans. a. Pyruvate. (Ref: Harper 30/e p161-167)
• Acetyl CoA condenses with Oxaloacetate to form From these options best answer is Pyruvate.
Citrate 5. Hyperammonemia inhibits TCA cycle by
• Oxidative phosphorylation occur in mitochondria depleting: (PGI June 2009)
by ETC a. Oxaloacetate
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• Krebs cycle cannot operate in anaerobic condition. b. Alpha ketoglutarate

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3. Which of the following substance binds to CoA c. Citrate

and condenses oxaloacetate to inhibit the TCA d. Succinyl CoA
cycle: (AIIMS Nov 2010) e. Fumarate
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408 |  
Self Assessment and Review of Biochemistry

Ans. b. Alpha ketoglutarate. (Ref: Harper 30/e p168) a. Atractyloside

Hyperammonemia, as occurs in advanced liver disease b. Oligomycin
and a number of (rare) genetic diseases of amino acid c. Rotenone
metabolism, leads to loss of consciousness, coma and d. Cyanide
convulsions, and may be fatal. This is because of the
Ans. a. Atractyloside. (Ref: Harper 30/e p132, 133)
withdrawal of α ketoglutarate to form glutamate
• Atractyloside inhibits oxidative phosphorylation by
(catalyzed by glutamate dehydrogenase) and then
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glutamine (catalyzed by glutamine synthetase), leading inhibiting the transporter of ADP into and ATP out
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to reduced concentrations of all citric acid cycle of the mitochondrion

intermediates, and hence reduced generation of ATP. • The antibiotic oligomycin completely blocks
oxidation and phosphorylation by blocking the flow
6. What is liberated when Citrate converted to Cis of protons through ATP synthase
Aconitate? (NBE pattern Q) • Barbiturates such as amobarbital, Rotenone and
a. H2O Piericidin A inhibit electron transport via Complex I
b. H2 • Antimycin A and dimercaprol inhibit the respiratory
c. H2O2 chain at Complex III. The classic poisons H2S, carbon
d. CO2 monoxide, and cyanide inhibit Complex IV and can
Ans. a. H2O. (Ref: Harper 30/e p163) therefore totally arrest respiration. Malonate is a
• Citrate isomerized to Isocitrate by Aconitase competitive inhibitor of Complex II.
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Reversible reaction
10. The electron flow in cytochrome C oxidase can be
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• The reaction occurs in two steps: dehydration to cis-

blocked by: (AIIMS May 2006)
aconitate and rehydration to isocitrate.
a. Rotenone
7. False about reducing equivalents is: b. Antimycin-A
(NBE pattern Q) c. Cyanide
a. They are NADH and NADPH d. Actinomycin
b. Only produced during primary metabolic Ans. c. Cyanide. (Ref: Harper 30/e p132,133)
pathway Cytochrome Oxidase is inhibited by CO, HCN, H2S and
c. Formed in TCA cycle Na Azide.
d. Formed in mitochondria
Ans. b. Only produced during primary metabolic 11. Cytosolic Cytochrome C mediates:
        pathway. (AIIMS May 2006)
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a. Apoptosis
8. High energy phosphate is not produced in:
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b. Electron transport
a. TCA cycle c. Krebs cycle
b. Hexose Mono Phosphate pathway d. Glycolysis
c. Glycolysis Ans. a. Apoptosis. (Ref: Harper 30/e p127-130)
d. Beta Oxidation of Fatty Acid Mitochondrial Cytochrome c is a mobile electron carrier
Ans. b. HMP Pathway. in Electron Transport Complex. This also mediates
Pathways which do not synthesize ATP are Apoptosis.
• HMP Pathway
• Rapaport Leubering Cycle 12. High energy compounds is/are: (PGI May 2012)
• Uronic acid pathway a. ATP
• Alpha oxidation of Fatty acid b. Creatine Phosphate
c. Glucose 1 Phosphate
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• Omega Oxidation of fatty acid

d. Glycerol 3 Phosphate
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Electron Transport Chain e. ADP

9. Transport of ADP in and ATP out of mitochondria Ans. a. ATP, b. Creatine Phosphate.
is inhibited by: (Nov 2010) (Ref: Harper 30/e p116)
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TCA Cycle and Biological Oxidation   | 409

Free Energy Free Energy Ans. c. Brown adipose tissue.

High Energy Compound kJ/mol Kcal/mol Brown adipose tissue contains thermogenin, which is a
Phosphoenolpyruvate -61.9 -14.8 physiological uncoupler of oxidative phosphorylation.
Carbamoyl phosphate -51.4 -12.3 This process is called Nonshivering Thermogenesis.
1,3-Bisphosphoglycerate (to -49.3 -11.8
3-phosphoglycerate) 16. Electron transport chain involves all except:
(Kerala 2011)
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Creatine phosphate -43.1 -10.3

a. NADP
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ATP→AMP + PPi -32.2 -7.7

ATP → ADP + Pi -30.5 -7.3 b. NAD
Glucose-1-phosphate -20.9 -5.0 c. Coenzyme Q
PPi -19.2 -4.6 d. FAD
Fructose-6-phosphate -15.9 -3.8 Ans. a. NADP.
Glucose-6-phosphate -13.8 -3.3
NADP is involved in reductive biosynthesis, not in ETC.
Glycerol-3-phosphate -9.2 -2.2
17. F0-F1 Complex, ATP synthase inhibitor is:
13. In ETC, oxidative phosphorylation (ATP (Kerala 2007)
formation) is regulated by: (PGI MAY 2011) a. Atractyloside
a. NADH CoQ reductase b. Oligomycin
b. Cytochrome C oxidase c. Antimycin
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c. Glutathione reductase d. Rotenone

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d. Isocitrate dehydrogenase Ans. b. Oligomycin. (Ref: Harper 29/e p127)

e. CoQ Cytochrome C reductase
• Atractyloside inhibits oxidative phosphorylation by
Ans. a, b, c, e. (Ref: Harper 30/e p130, 133) inhibiting the transporter of ADP into and ATP out
Components of the Electron Transport Chain Q are of the mitochondrion
contained in four large protein complexes:
• The antibiotic oligomycin completely blocks
• Complex I NADH CoQ Oxidoredutase oxidation and phosphorylation by blocking the flow
• Complex II CoQ Succinate Reductase of protons through ATP synthase.
• Complex III CoQ Cytochrome c Oxidoreductase
• Complex IV Cytochrome C Oxidase. 18. Respiratory Quotient 0.7 is seen in:
(NBE pattern Q)
14. Which component transfer four protons:
a. Carbohydrates
a. NADH-Q Oxidoreductase (PGI Nov 2009)
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b. Fat
b. Cytochrome-C Oxidase
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c. Protein
c. Cytochrome C–Q oxidoreductase
d. Isocitrate Dehydrogenase d. Alcohol
e. Succinate Q Reductase Ans. b. Fat.
Ans. a. NADH-Q Oxidoreductase, c. Cytochrome C–Q Respiratory Quotient
        oxidoreductase. (Ref: Harper 29/e p130) Measurement of the ratio of the volume of carbon dioxide
• Complex I and III pumps 4 H+ produced: volume of oxygen consumed
• Complex II pumps no protons (Respiratory Quotient, RQ) is an indication of the
• Complex IV pumps 2 H+. mixture of metabolic fuels being oxidized.
15. The specialized mammalian tissue/organ in RQ (CO2
which fuel oxidation serves not to produce ATP Metabolic Energy Yield produced/O2 Energy
fuel (kJ/g) consumed (kJ)/L O2
but to generate heat is: (AI 2006)
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Carbohydrate 16 1.00 20
a. Adrenal gland
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Protein 17 0.81 20
b. Skeletal music
c. Brown adipose tissue Fat 37 0.71 20

d. Heart Alcohol 29 0.66 20

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19. Phenobarbitone inhibits which complex of ETC: Dinitrophenol is an uncoupler of Oxidative Phospho-
(NBE pattern Q) rylation. So no ATP synthesis but electron transfer and
a. Complex I oxidation of reducing equivalents takes place.
b. Complex II
21. Mechanism of Cyanide poisoning: (NBE pattern Q)
c. Complex III a. Inhibition of Cytochrome Oxidase
d. Complex IV b. Inhibition of Carbonic Anhydrase
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Ans. a. Complex I. (Ref: Harper 30/e p133) c. Inhibition of Cytochrome c

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Inhibitors of ETC at Complex I d. Inhibition of ATP Synthase

• An insecticide and a fish Poison Rotenone Ans. a. Inhibition of Cytochrome Oxidase.
• Amobarbital which is a barbiturate (Ref: Harper 30/e p133)
• Piericidin. Inhibitors of Complex IV are CO, Cyanide, H2S, Sodium
Azide.
20. Dinitrophenol inhibits the electron transport
chain by: (NBE Pattern Q) 22. Final acceptor of electrons in ETC is:
a. Cytochrome b (AIIMS 2014 May)
b. Inhibit ATP synthesis and electron transport a. Cyt c
chain b. Oxygen
c. Inhibits ATP synthesis but not electron c. FADH2
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transport chain d. CoQ

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d. Inhibits electron transport chain but not ATP Ans. b. Oxygen. (Ref: Harper 30/e p133)
synthesis • Electrons are transferred in the ascending order of
Ans. c. Inhibit ATP synthesis and but not electron redox potential, the final oxygen electron acceptor
        transport chain. is oxygen.
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