THE CITRIC ACID CYCLE AND REGULATION

8/12/2019 THE CITRIC ACID CYCLE AND REGULATION

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THE CITRIC ACID CYCLEAND REGULATION

Assist. Prof.Dr. zlem Dalmzrak

Near East University

Faculty of Medicine

Department of Medical Biochemistry

Reference: Lehninger Principles of Biochemistry,5th Edition,

David L. Nelson and Michael M. Cox, Chapter:16, The Citric Acid Cycle


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In aerobic conditions, glucose is oxidized to

H2O and CO2.

This aerobic phase of catabolism is called

respiration.

In biochemical aspect, consuming O2and

producing CO2is called cellular respiration.

Sir Hans Adolf Krebs

1932 urea cycle identified

1937 citric acid cycle found

1953 Nobel Physiologi PrizeLaurate


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Cellular respiration occurs in three majorstages:

1. Organic fuel molecules (glucose, fattyacids and some amino acitds) are

oxidized to yield two-carbon fragments inthe form of the acetyl group of acetyl-coenzyme A.

2. Acetyl groups enter the citric acid cycle,which enzymatically oxidizes them to

CO2. The energy released is conserved inthe reduced electron carriers (NADH,FADH2).

3. Reduced coenzymes are oxidized, givingup protons (H+) and electrons. Theelectrons are tranferred to O2via chain of

electron-carrying molecules known asthe respiratory chain. In the course ofelectron transfer, the large amount ofenergy is conserved in the form of ATP(Oxidative phosphorylation).


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Production of Acetyl-CoA

Before entering the citric acid cycle, the carbon skeletons of sugars

and fatty acids are degraded to the acetyl group of acetyl-CoA.Many amino acid carbons also enter the cycle this way, although

several amino acids are degraded to other cycle intermediates.

Thiamine pyrophosphate (TPP)Flavin adenin dinucleotide (FAD)

Coenzyme A (CoA)

Nicotinamid adenine dinucleotide (NAD)

Lipoate


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Cryoelectron micrograph of PDH

Complex


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E1:Pyruvate

dehydrogenase

E2:Dihydrolipoyl

transacetylase

E3: Dihydrolipoyl

dehydrogenase

Pyruvate Dehydrogenase Complex


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Reactions of the Citric Acid Cycle


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1. Formation of Citrate


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The flexible domain of each subunit of Citrate Synthase undergoes

a large conformational change on binding of oxaloacetate :


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2. Formation of Isocitrate


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3. Oxidation of Isocitrate to -Ketoglutarate


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4. Oxidation of -Ketoglutarate to Succinyl-CoA


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5. Conversion of Succinyl-CoA to Succinate


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6. Oxidation of Succinate to Fumarate


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7. Hydration of Fumarate to Malate


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Fumarase does not catalyze cis-double bonds


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Some anaerobic microorganisms use an

incomplete citric acid cycle as a source

of biosynthetic precursors, not energy.

These anaerobs lack -ketoglutarate

dehydrogenase,therefore cannot carry

out complete cycle.


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TCA Cycle

Regulation


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2 Asetil-CoA + NAD++ 2H2

O Sksinat + 2CoA + NADH + H+

Glioksilat Dngs


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THE CITRIC ACID CYCLE AND REGULATION

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