Krebs cycle/ citric acid cycle/ tricarboxylic acid cycle TCA is the important topic from metabolism of carbohydrate in which we disscuss about cirtic acid cycle introduction, steps, regulation, energetics, important terms and lot more.

1. CITRIC ACID CYCLE
KREBS CYCLE OR
TRICARBOXYLIC ACID
TCA
HIMANSHU PANERU

2. # Content :
• Introduction
• History
• Location of TCA cycle
• Reaction of citric acid cycle
• Regeneration
• Requirement
• Energetics
• Regulation
• Clinical significance
• Notes

3. # INTRODUCTION :
■ citric acid cycle ( Krebs cycle or tricarboxylic acid - TCA ) is the most
important metabolic pathways for the energy supply to the body.
■ About 70% ATP synthesized in Kreb cycle.
■ Citric acid cycle essentially involve the oxidation of acetyl CoA to
carbon dioxide and water.
■ The citric acid cycle is final common oxidative pathway for
carbohydrates fats and amino acids.
■ This pathway is important for heme, glucose etc.
■ Krebs cycle is the central pathway which connect almost all the
individuals metabolic pathway ( either direct or indirect )

4. # HISTORY :
■ Citric acid cycle was proposed by HANS ADOLF KREBS in 1937 and
got Nobel Prize for his contribution in 1953

5. # LOCATION OF TCA CYCLE :
■ The enzyme of TCA cycle is located in mitochondrial matrix.

6. # TCA CYCLE OVERVIEW :
■ Krebs cycle basically involved with combination of two carbon Acetyl
CoA with a four carbon OXALOACETATE to produce six carbon
Tricarboxylic acid, citrate.
■ Oxaloacetate is considered to play a catalytic role in citric acid cycle

7. # RXN. OF CITRIC ACID CYCLE :
■ NOTE - Oxidative decarboxylation of pyruvate to acetyl CoA by
pyruvate dehydrogenase Complex this step is connecting linkage
between glycolysis and TCA cycle.

9. Step 1 FORMATION OF CITRATE : Krebs cycle properly start with the
condensation of acetyl coenzyme and oxaloacetate, catalyzed by the enzyme
citrate synthesis.
Step 2 and 3 : now citrate is isomerized To Isocitrate by the enzyme Aconites
this is done in Two Steps the intermediate product is Cis-Aconitate.
Step 4 and 5 FORNATION OF ALPHA KETOGLUTARATE : the enzyme isocitrate
dehydrogenase convert to oxalosuccinate then further to alpha-ketoglutarate
*the formation of NADH+H and liberating of Co2 occur here

10. Step 6 CONVERSION OF ALPHA KETOGLUTARATE TO SUCCINYL CoA : occur
through oxidative decarboxylation catalyzed by Alpha ketoglutarate
dehydrogenase
• At this stage of TCA cycle second NADH is produced and the second carbon
dioxide is liberated
Note - Alpha ketoglutarate dehydrogenase produce 3 enzymes and 5 coenzymes
• 5 Coenzymes are - TPP, NAD, CoA, FAD, Lipoic acid
Step 7 CONVERSION OF SUCCINATE : succinyl coenzyme is converted to
succinate in the presence of succinate thiokinase.
• This step is substrate level phosphorylation
• This reaction is coupled with the phosphorylation of GDP to GTP.
• GTP is converted to ATP by the enzyme nucleoside diphosphate kinaseGTP +
ADP ------ ATP + GDP

11. Step 8 FORMATIN OF FUMARATE : it is oxidised by succinate dehydrogenase
to fumarate
• this reaction produce FADH+H
Step 9 FORMATION OF MALATE : the enzyme fumarase catalyse the
conversion of fumarate to malate with the addition of water.
Step 10 CONVERSION OF MALATE TO OXALOACETATE : malate is then
oxidized to oxaloacetate by malate dehydrogenase
• The third or Final synthesis of NADH occur in this step
• The oxaloacetate is regenerated which can combine with another acetyl
coenzyme and repeat the process

12. # Regeneration of OXALOACETATE in
TCA cycle :
■ The TCA cycle is basically involve the oxidation of acetyl coenzyme to
carbon dioxide

13. # Requirement of OXYGEN in TCA cycle
:
■ There is no direct participation of oxygen in krebs cycle. TCA cycle
operate under aerobic condition

14. # Energetics of citric acid cycle :
■ During the process of oxidation of acetyl coenzyme Vai citric acid
cycle, 4 equivalents (3 as NADH and 1 as FAHD) is produced
■ Oxidation of 3 NADH Via electron transport chain

15. # REGULATION of citric acid cycle :
■ Three enzyme citrate synthesis, isocitrate dehydrogenase, Alpha
ketoglutarate dehydrogenase regulate the citric acid cycle
1) citrate synthesis is inhabited by ATP and NADH, acetyl coenzyme,
succinyl coenzyme
2) isocitrate dehydrogenase : is activated by ADP and inhabited by ATP
and NADH
3) Alpha ketoglutarate dehydrogenase : is inhabited by succinyl
coenzyme and NADH

16. # Amphibolic nature of TCA cycle :
■ The citric acid cycle provide various intermediate for synthesis of
compound needed by the body.
so krebs cycle is both catabolic and anabolic in nature

17. # Clinical significance :
1) krebs cycle is the final pathway of oxidation of glucose fat and
amino acid.
2) synthesis of citrate and gluconeogenesis.
3) complete oxidation of acetyl coenzyme
4) citric acid cycle is the central metabolic hub of the cell

18. # NOTE :
■ The number of ATP. produced in TCA cycle is 10 ATP

19. Thank you