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BIOCHEMISTRY
[B. Pharm – I Yr.]
Topic: Kreb’s Cycle/Citric acid cycle/TCA cycle
Umesh Kumar
Assistant Professor
Dept. of Pharm. Chemistry
Hygia Institute of Pharmaceutical Education and Research
CONTENTS
• Citric Acid Cycle
• Conversion of pyruvate (pathway)
• Introduction of TCA cycle
• Pathway of TCA cycle
• Energetics of TCA cycle
Conversion of Pyruvate into Acetyl CoA
• Pyruvate is converted to acetyl CoA by oxidative decarboxylation.
• This is an irreversible reaction, catalyzed by a multienzyme complex, known as pyruvate
dehydrogenase complex (PDH), which is found only in the mitochondria.
• High activities of PDH are found in cardiac muscle and kidney.
• The enzyme PDH requires five cofactors (coenzymes), namely-TPP, lipoamide, FAD, coenzyme A
and NAD+ (lipoamide contains lipoic acid linked to e-amino group of lysine). The overall reaction
of PDH is
Pathway for conversion of Pyruvate into Acetyl CoA
Complete Pathway for conversion of Pyruvate into Acetyl CoA
KREB’S CYCLE/ CITRIC ACID CYCLE/
TRICARBOXYLIC ACID CYCLE/ TCA
CYCLE
Citric acid cycle
• The citric acid cycle was proposed by Hans Adolf Krebs in 1937, based on the studies of oxygen
consumption in pigeon breast muscle.
• The cycle is named in his honour (Nobel Prize for Physiology and Medicine in 1953).
• About 65-70% of the ATP is synthesized in Krebs cycle.
• Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O.
• This cycle utilizes about two thirds of total oxygen consumed by the body.
• The name TCA cycle is used, since, at the outset of the cycle, tricarboxylic acids (citrate, cis-
aconitate and isocitrate) participate.
TCA Cycle – The central metabolic pathway
• The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino
acids.
• This cycle not only supplies energy but also provides many intermediates required for the synthesis
of amino acids, glucose, heme etc.
• Krebs cycle is the most important central pathway connecting almost all the individual metabolic
pathways (either directly or indirectly).
Location of TCA cycle
• The enzymes of TCA cycle are located in mitochondrial matrix, in close proximity to the electron
transport chain.
• This enables the synthesis of ATP by oxidative phosphorylation without any hindrance.
Mitochondria
Reactions of Citric acid cycles
• Oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase complex is
discussed above.
• This step is a connecting link between glycolysis and TCA cycle.
• The events of TCA cycle are;
• Formation of citrate – citrate synthase
• Isomerization of citrate – aconitase
• Formation of α-ketoglutarate – isocitrate dehydrogenase (ICD)
• Formation of α-ketoglutarate to succinyl CoA - α-ketoglutarate dehydrogenase
• Formation of succinate – succinate thiokinase
• Conversion of succinate to fumarate – succinate dehydrogenase
• Formation of malate – fumarase
• Conversion of malate into oxaloacetate – malate dehydrogenase (MDH)
Requirement of oxygen by TCA Cycle
• There is no direct participation of oxygen in Krebs cycle.
• However, the cycle operates only under aerobic conditions. This is due to the fact that NAD+ and FAD
(from NADH and FADH2, respectively) required for the operation of the cycle can be regenerated in
the respiratory chain only in the presence of O2.
Energetics of TCA cycle
• During the process of oxidation of acetyl CoA via citric acid cycle, 4 reducing equivalents (3 as
NADH and one as FADH2) are produced.
• Oxidation of 3 NADH by electron transport chain coupled with oxidative phosphorylation results in
the synthesis of 9 ATP, whereas FADH2 leads to the formation of 2 ATP.
• Besides, there is one substrate level phosphorylation. Thus, a total of twelve ATP are produced from
one acetyl CoA.
THANK YOU
HYGIA GROUP OF INSTITUTIONS
GHAILA ROAD, GAAZIPUR BALRAM,
FAIZULLAHGANJ, LUCKNOW

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Kreb's Cycle.pptx

  • 1. BIOCHEMISTRY [B. Pharm – I Yr.] Topic: Kreb’s Cycle/Citric acid cycle/TCA cycle Umesh Kumar Assistant Professor Dept. of Pharm. Chemistry Hygia Institute of Pharmaceutical Education and Research
  • 2. CONTENTS • Citric Acid Cycle • Conversion of pyruvate (pathway) • Introduction of TCA cycle • Pathway of TCA cycle • Energetics of TCA cycle
  • 3. Conversion of Pyruvate into Acetyl CoA • Pyruvate is converted to acetyl CoA by oxidative decarboxylation. • This is an irreversible reaction, catalyzed by a multienzyme complex, known as pyruvate dehydrogenase complex (PDH), which is found only in the mitochondria. • High activities of PDH are found in cardiac muscle and kidney. • The enzyme PDH requires five cofactors (coenzymes), namely-TPP, lipoamide, FAD, coenzyme A and NAD+ (lipoamide contains lipoic acid linked to e-amino group of lysine). The overall reaction of PDH is
  • 4. Pathway for conversion of Pyruvate into Acetyl CoA
  • 5. Complete Pathway for conversion of Pyruvate into Acetyl CoA
  • 6. KREB’S CYCLE/ CITRIC ACID CYCLE/ TRICARBOXYLIC ACID CYCLE/ TCA CYCLE
  • 7. Citric acid cycle • The citric acid cycle was proposed by Hans Adolf Krebs in 1937, based on the studies of oxygen consumption in pigeon breast muscle. • The cycle is named in his honour (Nobel Prize for Physiology and Medicine in 1953). • About 65-70% of the ATP is synthesized in Krebs cycle. • Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O. • This cycle utilizes about two thirds of total oxygen consumed by the body. • The name TCA cycle is used, since, at the outset of the cycle, tricarboxylic acids (citrate, cis- aconitate and isocitrate) participate.
  • 8. TCA Cycle – The central metabolic pathway • The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. • This cycle not only supplies energy but also provides many intermediates required for the synthesis of amino acids, glucose, heme etc. • Krebs cycle is the most important central pathway connecting almost all the individual metabolic pathways (either directly or indirectly). Location of TCA cycle • The enzymes of TCA cycle are located in mitochondrial matrix, in close proximity to the electron transport chain. • This enables the synthesis of ATP by oxidative phosphorylation without any hindrance.
  • 10. Reactions of Citric acid cycles • Oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase complex is discussed above. • This step is a connecting link between glycolysis and TCA cycle. • The events of TCA cycle are; • Formation of citrate – citrate synthase • Isomerization of citrate – aconitase • Formation of α-ketoglutarate – isocitrate dehydrogenase (ICD) • Formation of α-ketoglutarate to succinyl CoA - α-ketoglutarate dehydrogenase • Formation of succinate – succinate thiokinase • Conversion of succinate to fumarate – succinate dehydrogenase • Formation of malate – fumarase • Conversion of malate into oxaloacetate – malate dehydrogenase (MDH)
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  • 13. Requirement of oxygen by TCA Cycle • There is no direct participation of oxygen in Krebs cycle. • However, the cycle operates only under aerobic conditions. This is due to the fact that NAD+ and FAD (from NADH and FADH2, respectively) required for the operation of the cycle can be regenerated in the respiratory chain only in the presence of O2.
  • 14. Energetics of TCA cycle • During the process of oxidation of acetyl CoA via citric acid cycle, 4 reducing equivalents (3 as NADH and one as FADH2) are produced. • Oxidation of 3 NADH by electron transport chain coupled with oxidative phosphorylation results in the synthesis of 9 ATP, whereas FADH2 leads to the formation of 2 ATP. • Besides, there is one substrate level phosphorylation. Thus, a total of twelve ATP are produced from one acetyl CoA.
  • 15. THANK YOU HYGIA GROUP OF INSTITUTIONS GHAILA ROAD, GAAZIPUR BALRAM, FAIZULLAHGANJ, LUCKNOW