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CITRIC ACID CYCLE

Mrs. C.PushpanjaliLecturer

Department of Biochemistry

SRM Dental College

Ramapuram

C.P

➢TRICARBOXYLIC ACID CYCLE

➢KREBS CYCLE

➢ HANS KREBS IN 1937 PROPOSED THE REACTIONS OF THE CYCLE.

➢1953-NOBEL PRIZE

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HANS ADOLF KREBS

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DEFINITION

CYCLIC ARRANGEMENT OF THE SEQUENCE OF REACTIONS THAT CONVERT ACETYL COA TO TWO

MOLECULES CO2 IS CALLED CITRIC ACID CYCLE.

ENZYMES SITE-

Occur in the MITOCHONDRIAL MATRIX.

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CYCLIC PROCESS STARTS WITH OXALOACETATE AND GETS COMPLETE WITH REGENERATION OF OXALOACETATE.

THE CONVERSION OF ACETYL COA TO CO2 IN THE CYCLE GENERATES REDUCING

EQUIVALENTS.(NADH,FADH2)AND GTP.THE REDUCED COENZYMES ARE FINALLY OXIDISED IN THE

RESPIRATORY CHAIN WITH GENERATION OF ATP

ONE ACETYL COA MOLECULE IS OXIDISED AT A TIME.

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Pyruvate to Acetyl coa

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➢Pyruvate produced in cytosol and transported into Mitochondria.

1. First converted to Acetyl CoA by Pyruvate DehydrogenaseComplex.

2. Oxidative decarboxylation of pyruvate.

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OPERATES ONLY UNDER AEROBIC CONDITIONS.

MOST OF THE REACTION STEPS ARE IRREVERSIBLE.

MOST IMPORTANT ATP PRODUCING

ie MOST ENERGY PRODUCING CYCLE

AMPHIBOLIC ROLE-

BOTH ANABOLIC AND CATABOLIC

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THIS IS THE FINAL COMMON PATHWAY FOR CARBOHYDRATES,PROTEINS AND FATS.

SOME AMINOACIDS ARE DEGRADED TO INTERMEDIATES OF TCA CYCLE.ACETYL COA ARISES

FROM FAT CATABOLISM.

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IN THE LIVER INTERMEDIATES OF TCA CYCLE ARE USED FOR THE SYNTHESIS OF FATTY ACIDS

CHOLESTEROL,AMINOACIDS,GLUCOSE

MANY AMINOACIDS ENTER THE CYCLE

OXIDATION OCCURS

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➢IT IS THE FINAL COMMON OXIDATIVE PATHWAY THAT OXIDIZES ACETYL COA TO CO2.

➢IT IS THE SOURCE OF REDUCED COENZYMES THAT PROVIDE THE SUBSTRATE TO THE ETC.

➢IT ACTS AS A LINK B ETWEEN CATAB OLIC AND ANABOLICPATHWAYS.(Amphibolicrole.)

➢IT PROVIDES PRECUSORS FOR THE SYNTHESIS OF AMINO ACIDS AND N UCLEOTIDES.

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REACTIONS OF THE CYCLE➢PREPARATORY STEP:ACETYL COA ENTERS THE CYCLE ,AND

IS COMPLETELY OXIDIZED.DURING THIS PROCESS THE ENERGY IS TRAPPED.

➢CONVERSION OF PYRUVATE TO ACETYL COA➢PYRUVATE DH –MULTIENZYME COMPLEX➢TPP,COENZYME A,NAD,FAD,LIPOIC ACID

➢STEP1-FORMATION OF CITRATE AND ITS CONVERSION TO ISOCITRATE

➢STEP2-CONVERSION OF ISOCITRATE TO SUCCINYL COA

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STEPS OF THE TCA CYCLE

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STEP 4-FORMATION OF SUCCINYL- COA

STEP5-GENERATION OF SUCCINATE

STEP8-REGENERATION OF OXALO-ACETATE

STEP3-FORMATION OF ALPHA KETOGLUTARATE

STEP 6-FORMATION OF FUMARATESTEP6-Formation of fumarateSTEP 7-FORMATION OF MALATE

C.P

Department of Biochemistry 15C.P

INHIBITORS

➢FLUOROACETATE-ACONITASE

➢NON-COMPETITIVE

➢MALONATE-SUCCINATE DH

➢COMPETITIVE INHIBITOR

➢ARSENITE-ALPHAKETOGLUTARATE DH

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➢ OXIDATION OF 3 NADH BY ETC COUPLED WITH OXIDATION RESULTS IN THE SYNTHESIS OF 9 ATP

➢ FADHH2 LEADS TO THE FORMATION OF 2ATP’S

➢ ONE ATP IN SUBSTRATE LEVEL PHOSPHORYLATION

➢ TOTAL -12 ATP’S FROM ONE ACETYL COA

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➢Complete oxidation of Acetyl CoA-CO2 removal steps

➢ATP generating steps

➢Final common oxidative pathway

➢Integration of Major Metabolic pathways

➢Amphibolic role

➢Anaploretic Role

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Department of Biochemistry 19C.P

1. Sathyanarayana U., Chakrapani U., Textbook of Biochemistry, 4th

Edition, Elsevier, 1999.

2. Pankaja Naik, Essentials of Biochemistry, Jaypee Brothers Medical

Publishers, 2012.

3. Vasudevan D.M., Sreekumari S., Kannan Vaidyanathan, Textbook of

Biochemistry For Medical Students, 6th

Edition, Jaypee Brothers Medical

Publishers, 1995.

4. www.google.com