Metabolism ll - pyruvate dehydrogenase complex, substrate channeling, central role of TCA cycle, aconitase, anaplerosis, beta oxidation vs fatty acid synthesis

1. 10. SOME IMPORTANT QUESTION - ANSWER FOR IGNOU BIOCHEMISTRY [CHE 9]
METABOLISM - II
Q.1. Describe the conversion of pyruvate to acetyl CoA.[pyruvate क
े acetyl CoA में परिवर्तन
का वर्णन करें I]
Ans. Pyruvate, generated by glycolytic pathway, is transported into mitochondrial matrix where it
is converted into acetyl CoA(the starting material for TCA cycle) by a multienzyme complex
called pyruvate dehydrogenase complex. This complex contains three enzymes (pyruvate
dehydrogenase E1 (with prosthetic group TPP), dihydrolipoyl transacetylase E2 (with prosthetic
group lipoic acid) and dihydrolipoyl dehydrogenase E3 (with prosthetic group FAD) held together
by strong noncovalent interactions. In addition, coenzyme A and NAD+ are also required. The
overall reaction catalyzed by pyruvate dehydrogenase complex is oxidative decarboxylation
involving 5 consecutive reaction steps:
The first step is the decarboxylation of pyruvate catalyzed by E1 in which pyruvate reacts with
TPP of E1 and is decarboxylated to the hydroxyethyl derivative. In the second step is also
catalyzed by E1 which results in transfer of two electrons and acetyl group from TPP to the
oxidized form of lipoyllysyl group of the core enzyme dihydrolipoyl transacetylase, E2 to form the
acetyl thioester of the reduced lipoyl group. In the third step (transesterification) - SH group of
CoA replaces the - SH group of E2 to yield acetyl CoA and the fully reduced form of lipoyl group
of E2. In fourth step dihydrolipoyl dehydrogenase, E3 promotes the transfer of two hydrogen
atoms from the reduced lipoyl group of E2 to the FAD prosthetic group of E3 forming FADH2
and restoring the oxidized form of lipoyllysyl group of E2. In the fifth step the reduced FADH2 of
E3 transfers a hydride ion to NAD+ forming NADH. The enzyme complex is now ready for
another catalytic cycle. The long lipoyllysyl arm (formed by attachment of lipoate to the end of a
lysine side chain of E2) swings from the active site of E1 to E2 to E3, tethering the intermediates
to the enzyme complex to allow substrate channeling. The overall reaction is:
Pyruvate + CoA + NAD+ ---> acetyl CoA + CO2 + NADH + H+
[Glycolytic pathway द्वारा बना Pyruvate mitochondrial matrix में ट्रांसपोर्ट हो जाता है जहाँ यह acetyl
CoA (जो TCA cycle का starting material होता है) में, एक multienzyme complex - pyruvate
dehydrogenase complex, द्वारा परिवर्तित किया जाता है I इस complex में तीन enzymes (pyruvate
dehydrogenase E1 (prosthetic group TPP क
े साथ), dihydrolipoyl transacetylase E2 (prosthetic
group lipoic acid क
े साथ) और dihydrolipoyl dehydrogenase E3 (prosthetic group FAD क
े साथ) होते
हैं जो मजबूत noncovalent interactions द्वारा आपस में एक साथ संगठित रहते हैं I इसक
े अतिरिक्त ,
coenzyme A और NAD+ की भी आवश्यकता होती है I pyruvate dehydrogenase complex द्वारा
catalyzed reaction क
ु ल मिलाकर एक oxidative decarboxylation reaction है जिसमें लगातार पाँच
reaction steps शामिल होते हैं I
पहला step है pyruvate का decarboxylation जो E1 द्वारा catalyze होता है और इसमें pyruvate E1 क
े
TPP से react करक
े hydroxyethyl derivative में decarboxylate होता है I दूसरे चरण में, जो E1 द्वारा ही
catalyze होता है, TPP से दो electrons और acetyl group का E2 क
े lipoyllysyl group क
े oxidized form
को transfer होता है जिससे reduced lipoyl group का acetyl thioester बनता है I तीसरे चरण में (जिसमें
transesterification होता है) CoA का - SH group E2 क
े - SH group को प्रतिस्थापित करता है जिससे
acetyl CoA और E2 क
े lipoyl group का पूर्णतया reduced form प्राप्त होता है I चौथे चरण में, E3 दो
hydrogen atoms E2 क
े reduced lipoyl group से E3 क
े prosthetic group, FAD को ट्रांसफर करने में
1

2. सहायता करता है जिससे FADH2 बनता है और E2 क
े lipoyllysyl group का oxidized form पुनः स्थापित हो
जाता है I पांचवे चरण में E3 का reduced FADH2 NAD+ को एक hydride ट्रांसफर करक
े NADH बनाता है I
Enzyme complex अब एक और catalytic cycle हेतु पुनः तैयार हो जाता है I E2 की एक lysine side chain
क
े छोर पर lipoate क
े जुड़ने से बनी लम्बी lipoyllysyl arm E1 से E2 से E3 की active site को डोलती है और
intermediates (मध्यवर्ती उत्पादों) को enzyme complex से बांधे रखकर substrate की channeling को होने
देती है I क
ु ल मिलाकर अंतिम reaction इस प्रकार होता है :
Pyruvate + CoA + NAD+ ---> acetyl CoA + CO2 + NADH + H+
Q.2. Describe the phenomenon of substrate channeling observed in the conversion of
pyruvate to acetyl CoA. [pyruvate क
े acetyl CoA में परिवर्तन में प्रेक्षित(observed) substrate
channeling की परिघटना (phenomenon) का वर्णन करें I]
Ans. Pyruvate is converted into acetyl CoA in the mitochondrial matrix in presence of NAD+ and
the reaction is catalyzed by Pyruvate dehydrogenase complex which is a multienzyme complex
consisting of three distinct enzymes held together by strong noncovalent interactions.The
pyruvate undergoes decarboxylation (catalyzed by pyruvate dehydrogenase, E1), oxidation
(catalyzed by dihydrolipoyl transacetylase, E2) and condensation (catalyzed by dihydrolipoyl
dehydrogenase, E3). During all these three reactions none of the intermediates is released into
the medium. They remain attached to the enzyme complex and are transferred directly from one
enzyme to another. The long lipoyllysyl side chain of dihydrolipoyl transacetylase (E2) serves as
a "swinging arm" to transfer electrons from pyruvate to E1 to E2 to E3 and to transfer the acetyl
group from E1 to CoA. This phenomenon is called substrate channelling. Thus substrate
channelling is the passing of intermediary metabolic products of one enzyme directly to another
enzyme or active site without its release into the medium and thus keeping high concentration of
substrates for every enzyme of the complex and hence making the metabolic reactions more
efficient. It also conserves the scarce solvation capacity of the cell and enhances catalysis by
avoiding unfavorable energetics of desolvating substrates.
[Mitochondrial matrix में Pyruvate NAD+ की उपस्थिति में acetyl CoA में परिवर्तित हो जाता है और यह
reaction Pyruvate dehydrogenase complex (एक multienzyme complex) द्वारा catalyze होता है I इस
complex में तीन अलग - अलग enzymes होते हैं जो मजबूत noncovalent interactions द्वारा संगठित रहते
2

3. हैं I Pyruvate का सबसे पहले decarboxylation (catalyzed by pyruvate dehydrogenase, E1) होता है,
फिर oxidation (catalyzed by dihydrolipoyl transacetylase, E2) और अंत में condensation reaction
(catalyzed by dihydrolipoyl dehydrogenase, E3) होता है I इन सभी तीनों reactions क
े दौरान कोई भी
intermediate product medium में release नहीं होता है बल्कि ये enzyme complex से जुड़े रहते हैं और एक
enzyme से दूसरे enzyme को स्थानांतरित होते हैं I Dihydrolipoyl transacetylase (E2) की लम्बी
lipoyllysyl side chain एक "swinging arm" का काम करती है जो electrons को pyruvate से E1 को E2 को,
फिर E2 से E3 को और E1 से acetyl group को CoA को ट्रांसफर (स्थानांतरित) करने में मदद करती है I यह
परिघटना substrate channelling कहलाती है I इस प्रकार मध्यवर्ती (intermediary) metabolic products का
एक enzyme से सीधे दूसरे enzyme या active site को बिना reaction medium में मुक्त हुए स्थानांतरण
substrate channeling कहलाता है I इस कारण enzyme complex क
े प्रत्येक enzyme क
े लिए substrate की
अधिक मात्रा उपलब्ध रहती है और metabolic reactions अधिक प्रभावी होते हैं I यह cell की अल्प
विलायकयोजन (solvation) क्षमता को संरक्षित रखने सहायक होता है और catalysis को भी, desolvating
substrates की प्रतिक
ू ल energetics को टाल कर, बढ़ाता है I]
Q.3. Write the functions of TCA cycle.[TCA cycle क
े कार्य लिखें I]
Ans.
1. Oxidation of acetyl CoA coming from pyruvate, fatty acid oxidation and amino acids.
[Pyruvate, fatty acid oxidation और amino acids से प्राप्त acetyl CoA का oxidation करना I]
2. Formation of NADH and FADH2 which generates ATP through electron transport and
oxidative phosphorylation.
[NADH और FADH2 बनाना जो electron transport और oxidative phosphorylation द्वारा ATP
बनाते हैं I]
3. TCA cycle has both catabolic and anabolic potential, hence called an amphibolic
pathway. It not only brings about the oxidation of acetyl moiety of acetyl CoA to CO2 (i.e.
catabolic function) but also provides precursors such as succinate, α-ketoglutarate,
succinyl CoA and oxaloacetate for the biosynthesis of several compounds (i.e. anabolic
function).
[TCA cycle में अपचयी (catabolic) और उपचयी (anabolic) दोनों क्षमता होती है, इसीलिए इसे
amphibolic pathway कहते हैं I यह न क
े वल acetyl CoA की acetyl moiety का CO2 में oxidation
(यानि अपचयी कार्य) करता है बल्कि क
ु छ precursors (जैसे - succinate, α-ketoglutarate,
succinyl CoA और oxaloacetate) भी प्रदान करता है जो कई compounds की biosynthesis में
काम आते हैं (यानि अपचय कार्य) I]
4. Responsible for huge amounts of energy release and supply during aerobic respiration.
[यह cycle aerobic respiration में बड़ी मात्रा में ऊर्जा को मुक्त करने और आपूर्ति करने क
े लिए
ज़िम्मेदार होती है I]
Q.4. Describe the mechanism of action of aconitase in the conversion of citrate to
isocitrate.[citrate क
े isocitrate में परिवर्तन में aconitase enzyme की mechanism of action लिखें
I]
Ans. Aconitase, an iron-sulphur protein, catalyses the 2nd reaction of TCA cycle i.e. the
conversion of citrate to isocitrate with an intermediate formation of cis-aconitate. The interesting
3

4. feature in this isomerization reaction is that the symmetrical (achiral) citrate compound is
converted to asymmetrical (chiral) isocitrate. The enzyme has specific complementary sites for
binding OH, COO- and CH2COO- groups. Although citrate has two CH2COO- groups but the
enzyme can bind only one CH2COO-, and the other CH2COO- remains exposed. This is
because OH and COO- groups which are also bound to the binding site on the enzyme cannot
interchange their position resulting in an unsymmetrical 3-point attachment of citrate to the
enzyme, aconitase. The reaction proceeds by removal of a water molecule from citrate to
produce cis-aconitate followed by addition of water molecule to cis-aconitate to give isocitrate.
The cis-aconitate remains bound to the enzyme during the course of the reaction.
[Aconitase एक iron-sulphur protein है जो TCA cycle क
े दूसरे reaction यानि citrate क
े cis-aconitate
नामक मध्यवर्ती उत्पाद क
े साथ isocitrate में परिवर्तन को catalyze करता है I इस isomerization reaction
की ख़ास बात यह है कि citrate जो एक symmetrical (achiral) compound है, वो एक asymmetrical
(chiral) compound isocitrate में परिवर्तित होता है I इस enzyme में OH, COO- और CH2COO- groups
क
े लिए विशिष्ट पूरक (specific complementary) binding sites होती हैं I हालांकि citrate में दो CH2COO-
group होते हैं किन्तु enzyme क
े वल एक CH2COO- को bind कर सकता है और दूसरा CH2COO- group
खुला रहता है I ऐसा इसलिए होता है क्योंकि OH और COO- groups भी enzyme की bindsite से bind रहते हैं
और ये अपनी position का आदान - प्रदान नहीं कर सकते जिसक
े परिणामस्वरुप citrate की aconitase
enzyme क
े साथ एक unsymmetrical 3-point attachment हो पाता है I यह reaction citrate से एक water
molecule क
े हटने और cis-aconitate क
े बनने क
े साथ आगे बढ़ता है और फिर एक water molecule
cis-aconitate में जुड़ने से isocitrate बन जाता है I इस पूरे reaction क
े दौरान cis-aconitate enzyme से जुड़ा
रहता है I]
Q.5. Write short note on anaplerosis.[anaplerosis पर एक संक्षिप्त टिप्पणी लिखें]
Ans. The process of replenishment of depleted metabolic cycle or pathway intermediates is
called anaplerosis and the reactions which replenish intermediates of a metabolic pathway are
called anaplerotic reactions. Example: the formation of oxaloacetate from Pyruvate, CO2 and
ATP catalyzed by pyruvate carboxylase. This reaction replenishes the supply of oxaloacetate for
the TCA cycle in case the concentration of oxaloacetate decreases for some reason. However,
the availability of pyruvate is also important for this anaplerosis.
[Metabolic cycle या pathway क
े व्यय हुए मध्यवर्ती उत्पादों (intermediates) की पुनः पूर्ति प्रक्रिया को
anaplerosis कहते हैं और जिन reactions द्वारा इन मध्यवर्ती उत्पादों की पुनः पूर्ति होती है उन्हें anaplerotic
reactions कहते हैं I उदाहरण - pyruvate, CO2 और ATP से pyruvate carboxylase enzyme की उपस्थिति
में oxaloacetate का बनना I इस reaction द्वारा oxaloacetate की TCA cycle हेतु पुनः पूर्ति होती है, यदि
oxaloacetate का concentration किसी कारणवश कम हो जाए तो I हालांकि, इस anaplerosis हेतु pyruvate
की उपलब्धता भी महत्वपूर्ण होती है I]
pyruvate carboxylase
Pyruvate + CO2 + ATP ------------------------------> oxaloacetate + ADP + Pi
Another anaplerotic reaction -
PEP carboxykinase
PEP + CO2+ GDP —------------------------> oxaloacetate + GTP
4

5. Q.6. Why is it necessary to include a certain amount of carbohydrates in the diet for a
person trying to lose weight by burning some of the body fats?[यदि कोई व्यक्ति अपने body
की चर्बी को जला कर अपना वजन कम करना चाह रहा है तो उसक
े आहार में carbohydrates की क
ु छ मात्रा
शामिल करना क्यों अनिवार्य होता है?]
Ans. The fats are degraded to acetyl CoA which is metabolized via TCA cycle and for this,
adequate supply of pyruvate is required for maintaining the optimum levels of TCA cycle
intermediates and to ensure an efficient running of the cycle. Since the major source of pyruvate
is the glycolytic breakdown of carbohydrates, therefore, about one-fifth of the calorie or energy
requirements of such persons must be provided as dietary carbohydrates so that the fats could
be catabolized efficiently.
[वसा (fats) का क्षरण (degradation) होने पर acetyl CoA प्राप्त होता है जिसका TCA cycle द्वारा आगे
चयापचय होता है और इसक
े लिए pyruvate की पर्याप्त मात्रा की आवश्यकता होती है ताकि TCA cycle क
े
मध्यवर्ती उत्पादों (intermediates) का पर्याप्त स्तर बना रहे जिससे TCA cycle उचित क्षमता से चलती रहे I
चूंकि pyruvate का मुख्य स्रोत glycolysis द्वारा carbohydrates का breakdown होता है इसलिए किसी
व्यक्ति क
े लिए आवश्यक calorie या ऊर्जा का लगभग पांचवा हिस्सा भोजन क
े carbohydrates से प्राप्त होना
चाहिए ताकि fats का अपचय (catabolism) उचित रूप से हो सक
े I]
Q.7. Describe the central role played by TCA cycle in metabolism. [चयापचय में TCA cycle क
े
क
ें द्रीय भूमिका का वर्णन करें I
Ans. The TCA cycle plays a central role in metabolism by helping degradation as well as
synthesis of biomolecules. That is why it referred to as an amphibolic pathway. The acetyl CoA ,
produced from the catabolism of fatty acids and from pyruvate (produced from the catabolism
of carbohydrates and amino acids), is oxidized via TCA cycle. Several amino acids are
metabolized by their conversion into α- ketoglutarate and oxaloacetate, both of which are
intermediates of TCA cycle. Some of the intermediates of this cycle are precursors of
biosynthesis of some biomolecules e.g. citrate for biosynthesis of fatty acids, cholesterol and
steroids; α- ketoglutarate for biosynthesis of glutamate, glutamine and purine bases; succinyl
CoA for heme and porphyrin groups and oxaloacetate for biosynthesis of glucose, amino acids,
purine and pyrimidine bases.
Oxaloacetate plays a catalytic role in TCA cycle as it is regenerated on completion of the cycle.
Further, when any intermediate's concentration in TCA cycle decreases for any reason then it is
replenished to ensure the efficient running of the cycle. This replenishment of any intermediate
of the cycle is called 'anaplerosis'. For example: When oxaloacetate is drawn as precursor for
biosynthesis of some other molecule then it is replenished by carboxylation of pyruvate in
presence of enzyme pyruvate carboxylase and ATP. However, availability of pyruvate is
essential for anaplerosis and for the efficient running of TCA cycle. In this way the TCA cycle
plays a central role in metabolism.
[TCA cycle biomolecules क
े क्षरण (degradation) और संश्लेषण में मदद करक
े चयापचय (metabolism) में
एक क
ें द्रीय भूमिका निभाती है I इसीलिए इसे एक उभयचर मार्ग (amphibolic pathway) कहते हैं I Fatty acids
की catabolism और pyruvate (जो carbohydrates और amino acids की catabolism से प्राप्त होता है) से
जो acetyl CoA प्राप्त होता है वो TCA cycle द्वारा ही oxidize होता है I कई amino acids का चयापचय उनक
े
α- ketoglutarate और oxaloacetate में परिवर्तन द्वारा होता है और ये दोनों compounds TCA cycle क
े
मध्यवर्ती उत्पाद हैं I इसी प्रकार इस cycle क
े क
ु छ मध्यवर्ती उत्पाद क
ु छ biomolecules की biosynthesis क
े
लिए अग्रदूत (precursors) होते हैं, जैसे - fatty acids, cholesterol एवं steroids क
े जैव संश्लेषण हेतु citrate;
glutamate, glutamine और purine bases क
े जैव संश्लेषण हेतु α- ketoglutarate ; heme और porphyrin
5

6. groups क
े जैव संश्लेषण हेतु succinyl CoA और glucose, amino acids, purine और pyrimidine bases क
े
जैव संश्लेषण हेतु oxaloacetate अग्रदूत का काम करते हैं I Oxaloacetate TCA cycle में एक catalyst की
भूमिका निभाता है क्योंकि इस cycle क
े पूरा होने पर इसका पुनर्जनन (regeneration) हो जाता है I इसक
े साथ
ही, जब TCA cycle क
े दौरान किसी मध्यवर्ती उत्पाद का concentration किसी कारणवश कम हो जाता है तो
उसकी प्रतिपूर्ति हो जाती है ताकि cycle पूरी क्षमता क
े साथ चलती रहे I इस मध्यवर्ती उत्पादों की प्रतिपूर्ति को
'anaplerosis' कहते हैं I जैसे - जब किसी अन्य molecule क
े जैव संश्लेषण हेतु oxaloacetate का उपयोग होता
है तो इसकी प्रतिपूर्ति pyruvate क
े ATP और enzyme pyruvate carboxylase की उपस्थिति में
carboxylation द्वारा होती है I हालांकि, इस प्रतिपूर्ति और cycle क
े पूरी क्षमता क
े साथ चलने हेतु pyruvate की
उपलब्धता आवश्यक होती है I इस तरह TCA cycle चयापचय (metabolism) में एक क
ें द्रीय भूमिका निभाती है
I]
Q.8. Write a short note on regulation of TCA cycle.[TCA cycle क
े नियंत्रण पर एक संक्षिप्त
टिप्पणी लिखें I]
Ans. The TCA cycle has a central position in the final oxidation of acetyl moiety of acetyl CoA
coming from catabolism of carbohydrates, fats and some amino acids. Further, the cycle
provides precursors for some anabolic processes. Hence, its control is very important to provide
efficient and required energy production and precursors for biosynthetic pathways.
[Carbohydrates, fats और क
ु छ amino acids की catabolism से उत्पन्न acetyl CoA की acetyl moiety क
े
अंतिम oxidation में TCA cycle की क
ें द्रीय स्थिति होती है I साथ ही, यह cycle क
ु छ anabolic प्रक्रियाओं क
े
लिए अग्रदूत (precursors) उपलब्ध कराती है I इसलिए आवश्यक ऊर्जा और जैव संश्लेषण मार्गोँ (pathways) क
े
लिए अग्रदूत उपलब्ध कराने हेतु इसका नियंत्रण भी बहुत महत्वपूर्ण होता है I]
There are three control points of TCA cycle (TCA cycle क
े तीन नियंत्रण बिंदु होते हैं):
● Citrate synthase
● Isocitrate dehydrogenase
● α-ketoglutarate dehydrogenase complex
Citrate synthase: is inhibited by high energy charge (increased ATP in adenylate pool) and
NADH. The presence of ATP increases the Km of citrate synthase for acetyl CoA resulting in
decreased formation of citrate. A low NADH/NAD+ ratio favours the formation of citrate.
[Citrate synthase high energy charge (यानि adenylate pool में ATP की अधिकता) और NADH द्वारा
inhibit होता है I ATP की उपस्थिति में citrate synthase का acetyl CoA क
े लिए Km बढ़ जाता है जिससे
citrate का बनना कम हो जाता है I NADH/NAD+ का कम अनुपात citrate क
े बनने का समर्थन करता है I]
Isocitrate dehydrogenase : The conversion of isocitrate to α-ketoglutarate is catalyzed by this
enzyme and it is negatively regulated by NADH and ATP and positively regulated by NAD+ and
ADP.
[Isocitrate का α-ketoglutarate में परिवर्तन Isocitrate dehydrogenase enzyme द्वारा catalyze होता है
और यह enzyme NADH एवं ATP द्वारा नकारात्मक रूप से नियंत्रित होता है और NAD+ एवं ADP द्वारा
सकारात्मक रूप से नियंत्रित होता है I]
α-ketoglutarate dehydrogenase complex: catalyzes the third control point in TCA cycle i.e. the
conversion of α-ketoglutarate to succinyl CoA. This enzyme is inhibited by succinyl CoA, NADH
and high ATP concentration. When this enzyme is inhibited α-ketoglutarate accumulates.
However, α-ketoglutarate can be converted to glutamate needed for protein synthesis and
amino acid synthesis. The enzyme is activated by low ATP and NADH.
[α-ketoglutarate dehydrogenase complex α-ketoglutarate क
े succinyl CoA में परिवर्तन को catalyze
करता है जोकि TCA cycle में तीसरा नियंत्रण बिंदु है I यह enzyme succinyl CoA, NADH और ATP क
े
अधिक concentration द्वारा inhibit होता है I जब यह enzyme inhibit होता है तो α-ketoglutarate एकत्रित
6

7. होता है I हालांकि, α-ketoglutarate को protein और amino acid क
े संश्लेषण क
े लिए आवश्यक glutamate में
परिवर्तित किया जा सकता है I यह enzyme ATP और NADH क
े कम होने पर activate हो जाता है I इस प्रकार
शरीर की आवश्यकतानुसार TCA cycle का परिचालन नियंत्रित होता है I]
Q.9. Calculate how many ATPs are consumed in conversion of two molecules of pyruvate
to one molecule of glucose via gluconeogenesis. How is it different from the ATPs
generated in conversion of one molecule of glucose to two pyruvate molecules via
glycolysis?[pyruvate क
े दो molecules क
े glucose क
े एक molecule में gluconeogenesis द्वारा
परिवर्तन में कितने ATP उपभुक्त होते हैं? और यह glucose क
े एक molecule क
े pyruvate क
े दो
molecules में glycolysis द्वारा परिवर्तन में मुक्त हुए ATP से किस प्रकार भिन्न है?]
Ans. Six ATPs are consumed in conversion of two molecules of pyruvate into one molecule of
glucose via gluconeogenesis as under [pyruvate क
े दो molecules क
े gluconeogenesis द्वारा
glucose क
े एक molecule में परिवर्तन होने में ATP क
े 6 molecules उपभुक्त होते हैं] :
Pyruvate → oxaloacetate --- 1 ATP used
Oxaloacetate → phosphoenolpyruvate ----- 1 GTP used (equivalent to 1ATP)
3 - P - glycerate → 1,3 - bis- P- glycerate ---- 1 ATP used
Thus 3 ATPs are used by one pyruvate but since two pyruvate molecules are converted into one
glucose molecule, in all 6 ATPs are used. [इस प्रकार एक pyruvate द्वारा 3 ATP उपभुक्त होते हैं लेकिन
दो pyruvate molecules क
े एक glucose molecule में परिवर्तन होने पर 6 ATP उपभुक्त होते हैं I]
In contrast, glycolytic breakdown of one glucose molecule into two pyruvate molecules
generates only two ATPs. [इसक
े विपरीत, glucose क
े एक molecule क
े दो pyruvate molecules में
glycolysis द्वारा परिवर्तन में दो ATP बनते हैं I]
Glucose → Glucose-6-P —-- 1 ATP used
Fr-6-P → Fr-1,6-bis-P —--- 1 ATP used
2 × (1,3-bis-P-glycerate) → 2 × (3-P-glycerate) —--- 2 ATP produced
2 × (phosphoenolpyruvate) → 2 × (pyruvate) —--- 2 ATP produced
—-----------------------------------------------------------------------------------------
Net gain of ATP = 2
Thus expenditure of four extra high energy bonds (ATPs) is required to drive the otherwise
thermodynamically "uphill" process of the formation of glucose from pyruvate via
gluconeogenesis as compared to net two ATP produced in breakdown of one glucose molecule
to two molecules of pyruvate.
[इसप्रकार gluconeogenesis द्वारा pyruvate से glucose बनने क
े थर्मोडायनामिक रूप से कठिन कार्य में चार
अतिरिक्त ATP की आवश्यकता पड़ती है, glucose क
े pyruvate में glycolysis द्वारा बनने में 2 ATP उत्पन्न
होने क
े मुकाबले I]
Q.10. How many ATPs are generated in complete oxidation of one molecule of glucose
via glycolysis, TCA cycle and electron transport? And how many ATPs are formed on
complete oxidation of glucose unit of Glycogen? Show calculations.[एक ग्लूकोस molecule
क
े glycolysis, TCA cycle और electron transport द्वारा पूर्ण oxidation पर कितने ATP बनते हैं? और
glycogen क
े एक glucose unit क
े पूर्ण oxidation पर कितने ATP बनते हैं?]
Ans.
1. GLYCOLYSIS:
Glucose → 2 pyruvate ---- 2 ATP synthesized + 2 NADH formed (give 2×3=6 ATP via oxidative
phosphorylation/electron transport)* = net gain of ATP is 8 molecules.
2. CONVERSION OF PYRUVATE TO ACETYL COA:
7

8. 2 pyruvate → 2 acetyl CoA ----- 2 NADH (give 2×3=6 ATP)*
3. TCA CYCLE:
2 acetyl CoA → 4CO2 + 2CoA ---- 2 ATP synthesized (via GTP) + 6 NADH (give 3×6 =18 ATP
via oxidative phosphorylation)* + 2 FADH2 (give 2×2= 4 ATP via oxidative phosphorylation)*=
total 24 ATP molecules.
Combining 1, 2 and 3 would give 38 ATP molecules. Thus complete oxidation of glucose would
give 38 ATP molecules.
* [Oxidation of each NADH molecule gives 3 ATP and FADH2 gives 2 ATP molecules (electron
transport chain coupled ATP synthesis)]
However, glucose unit derived from glycogen upon oxidation would give a total of 39 ATP
because Glycogen is acted upon by enzyme Glycogen phosphorylase giving
Glucose-1-phosphate which is converted into glucose-6-phosphate by phosphoglucomutase.
Thus no ATP was used in the formation of glucose-6-phosphate. Hence, 3 ATP molecules are
synthesized during glycolysis instead of 2. Therefore, complete oxidation of glucose unit of
Glycogen will give rise to net synthesis of 39 ATP molecules.
Q.11. Why the oxidative degradation pathway of fatty acids is called beta - oxidation
pathway?[fatty acids क
े oxidative क्षरण (degradation) को beta-oxidation pathway क्यों कहते हैं
I]
Ans. Since the carbon atom adjacent to the carboxyl group of a fatty acid is known as alpha
carbon and the carbon next to alpha carbon is called beta carbon and the two hydrogen atoms
attached to it make the methylene group. In metabolic breakdown of fatty acid the beta-
methylene group of acyl-CoA is oxidized to a keto group. That is why this oxidative degradation
of fatty acid is called the beta - oxidation pathway.
[चूंकि एक fatty acid क
े carboxyl group क
े निकटस्थ carbon atom को alpha carbon और इसक
े अगले
carbon को beta carbon कहते हैं I इसी beta carbon से दो hydrogen atom जुड़कर beta-methylene
group बनाते हैं I Fatty acid क
े breakdown में acyl CoA क
े beta-methylene group का keto group में
oxidation होता है, इसीलिए fatty acid क
े ऑक्सीकरणी क्षरण (oxidative degradation) को beta-oxidation
कहते हैं I]
Q.12. Differentiate between fatty acid biosynthesis and beta-oxidation of fatty acids.[fatty
acid की जैव संश्लेषण (biosynthesis) और fatty acids क
े beta-oxidation में अंतर बतायें I]
Ans.
● Fatty acid biosynthesis occurs in cytoplasm whereas beta- oxidation occurs in
mitochondria and peroxisomes.
[Fatty acid biosynthesis cytoplasm में होती है जबकि beta- oxidation mitochondria और
peroxisomes में होता है I]
● The enzymes involved in fatty acid biosynthesis (fatty acid synthase) exist either as a
strong multienzyme complex (bacteria) or joined together covalently in a single protein
(higher organisms) whereas the enzymes of fatty acid degradation seem to exist
independently.
[Fatty acid biosynthesis क
े enzymes (fatty acid synthase) एक मजबूत multienzyme
complex क
े रूप में (जैसे bacteria में) या फिर एक सहसंयोजक बंधन (covalent bonds) द्वारा आपस
में जुड़कर एक प्रोटीन क
े रूप में (जैसे उच्चतर जीवों में) होते हैं, जबकि fatty acid oxidation क
े
enzymes स्वतंत्र रूप में रहते हैं I]
8

9. ● In beta oxidation of fatty acids the acyl group is always attached to the SH group of
coenzyme A whereas in biosynthesis it is attached to the SH group of the prosthetic
group of a specific protein called acyl carrier protein (ACP).
[Beta oxidation में acyl group coenzyme A क
े SH group से हमेशा जुड़ा रहता है जबकि
biosynthesis में यह एक विशिष्ट प्रोटीन acyl carrier protein (ACP) क
े SH group से जुड़ा होता है I]
● The oxidants in fatty acid oxidation are FAD and NAD+ while in biosynthesis the
reductant is NADPH.
[Fatty acid oxidation में FAD और NAD+ oxidants इस्तेमाल होते हैं जबकि biosynthesis में
NADPH reductant इस्तेमाल होता है I]
● More energy is spent in fatty acid biosynthesis than what is obtained by fatty acid
oxidation.
[Fatty acid biosynthesis में fatty acid oxidation से प्राप्त ऊर्जा की तुलना में अधिक ऊर्जा खर्च होती
है I]
Q.13. Mention briefly how triacylglycerols are metabolized. [Triglycerides का चयापचय किस
प्रकार होता है, संक्षेप में लिखें I]
Ans. Triacylglycerols are hydrolysed in cytoplasm by various lipases into glycerol and fatty
acids. Glycerol is phosphorylated and oxidized to dihydroxyacetone phosphate which is
isomerises to glyceraldehyde-3-phosphate which then metabolizes via glycolytic pathway, TCA
cycle and electron transport chain. Each fatty acid released from triacylglycerol is converted into
the corresponding acyl-CoA which is transported from cytoplasm to mitochondrial matrix where
acyl-CoA undergoes a sequence of reactions (oxidation, hydration, another oxidation and
thiolytic cleavage) called beta-oxidation and the aliphatic chain of acyl-CoA is broken down into
several acetyl CoA molecules. These acetyl CoA are further oxidized via TCA cycle and
electron transport chain.
[Triacylglycerols विभिन्न lipase enzymes द्वारा cytoplasm में glycerol और fatty acids में hydrolyse
होते हैं I फिर Glycerol क
े phosphorylation और oxidation से dihydroxyacetone phosphate बनता है जो
glyceraldehyde-3-phosphate में isomerise होता है I Glyceraldehyde-3-phosphate glycolysis, TCA
cycle और electron transport chain द्वारा metabolize होता है I Triacylglycerol से मुक्त हुआ प्रत्येक fatty
acid अपने समरूपी acyl-CoA में परिवर्तित होता है जो cytoplasm से mitochondrial matrix में ट्रांसपोर्ट हो
जाता है जहाँ acyl-CoA क्रम से होने वाले कई reactions (oxidation, hydration, another oxidation और
thiolytic cleavage) से गुजरता है, जिसे beta-oxidation कहते हैं, और इस तरह acyl-CoA की aliphatic
chain कई acetyl CoA molecules में टूट जाती है I ये acetyl CoA molecules फिर TCA cycle और
electron transport chain द्वारा oxidize होते हैं I]
Q. 14. Fill in the blanks:
(i) The conversion of pyruvate to acetyl CoA is catalyzed by _______.
(ii) The pyruvate dehydrogenase complex consists of _______ enzymes.
(iii) TCA cycle occurs in _______ of the cell.
(iv) In the conversion of pyruvate to acetyl CoA by pyruvate dehydrogenase complex none of
the intermediates is released into the medium as they remain attached to the enzyme complex
and this phenomenon is known as ______________.
(v) Kreb's cycle is also called as citric acid cycle because the first product formed in the cycle is
______.
(vi) Kreb's cycle is called tricarboxylic acid cycle because the first product of the cycle is citric
acid which contains three ______ groups.
9

10. (vii) Before entering the TCA cycle, pyruvate is converted to _______
(viii) The availability of _______ is critical for anaplerosis and for the efficient running of the TCA
cycle.
(ix) A certain amount of _______ in the diet of persons trying to lose weight by burning some of
the body fats.
(x) TCA cycle has both catabolic and anabolic potential, hence called an _______ pathway.
(xi) The conversion of citrate to isocitrate is catalyzed by enzyme _______.
(xii) The process of replenishment of depleted metabolic cycle or pathway intermediates is
called _______.
(xiii) The formation of oxaloacetate from pyruvate, CO2 and ATP catalyzed by pyruvate
carboxylase replenishes the supply of _______ for the TCA cycle.
(xiv) The three control points of TCA cycle are Citrate synthase, Isocitrate dehydrogenase and
________.
(xv) _____ ATPs are consumed in conversion of two molecules of pyruvate into one molecule of
glucose via gluconeogenesis.
(xvi) The glycolytic breakdown of one glucose molecule into two pyruvate molecules generates
only ____ ATPs.
(xvii) The complete oxidation of one molecule of glucose via glycolysis, TCA cycle and electron
transport results in generation of ______ ATPs.
(xviii) Fatty acid biosynthesis occurs in ______ whereas beta-oxidation occurs in _______ and
peroxisomes.
(xix) More energy is spent in fatty acid ______ than what is obtained by fatty acid ______.
(xx) The fatty acid synthase in bacteria exists as a strong _______ complex.
(xxi) In beta oxidation of palmitoyl-CoA (C15H31COSCoA) _____ cycles of beta oxidation
pathway will be required for the complete breakdown of palmitoyl-CoA giving rise to _______
molecules of acetyl CoA.
Ans. (i) Pyruvate dehydrogenase complex, (ii) three, (iii) mitochondria, (iv) substrate channeling,
(v) citric acid, (vi) carboxyl, (vii) acetyl CoA, (viii) pyruvate, (ix) carbohydrates, (x) amphibolic,
(xi) aconitase, (xii) anaplerosis, (xiii) oxaloacetate, (xiv) α-ketoglutarate dehydrogenase
complex, (xv) six, (xvi) two, (xvii) 38, (xviii) cytoplasm, mitochondria, (xix) biosynthesis,
oxidation, (xx) multienzyme, (xxi) seven, eight
REFERENCES:
1. IGNOU, CHE - 9 Biochemistry, Block 3
2. Lehninger Principles of biochemistry, seventh edition ; David L. Nelson & Michael M. Cox.
Disclaimer : The pictures given in the text have been downloaded from Google images and I am
thankful to the persons who have uploaded these pictures.
Dr. P. K. Nigam (Retired Biochemist)
10