citric acid presentation

7/30/2019 citric acid presentation

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THE CITRIC ACID CYCLE


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OVERVIEW

The Citric Acid Cycle is also called theTricarboxylic Acid Cycle (TCA Cycle) or the Krebs Cycle It is the major energy-producing pathwayin the bodyThe cycle occurs in the mitochondria


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The cycle starts with the 4-carboncompound oxaloacetate, adds 2 carbonsfrom acetyl Co-A, loses 2 carbons ascarbon dioxide, and regenerates the 4-carbon compound oxaloacetateElectrons are transferred by the cycle toNAD+ and FAD


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As the electrons are passed to oxygenby the electron transport chain, ATP isgenerated by oxidative phosphorylation

ATP from the cycle is also generatedfrom GTP, via substrate levelphosphorylation


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THE REACTIONS OF THECITRIC ACID CYLE


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ACETYL COENZYME A CONDENSES WITHOXALOACETATE TO FORM CITRATE

Enzyme: Citrate synthaseCleavage of the high-energy thioester bond inacetyl CoA provides the energy for this

condensationCitrate, the product, inhibits this reaction


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CITRATE IS ISOMERIZED TO ISOCITRATE BYMOLECULAR REARRANGEMENT

Aconitate serves as an enzyme-boundintermediateEnzyme: Aconitase


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ISOCITRATE IS OXIDIZED TOa -KETOGLUTARATE

This is the first oxidative decarboxlation reaction inthe TCA cycleCarbon dioxide is produced

Electrons are passed to NAD+

to form NADH + H+

Enzyme: Isocitrate dehydrogenase, allostericallyactivated by ADP and inhibited by NADH


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a -KETOGLUTARATE IS CONVERTED TOSUCCINYL COENZYME A

This is the second oxidative decarboxylation reactionCarbon dioxide is releasedThe keto-group of a -ketoglutarate is oxidized to an

acid, which combines with CoASH to form succinylCoANADH + H + are produced


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The enzyme for this reaction is called a -ketoglutarate dehydrogenase, and requires five

cofactors


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SUCCINYL COENZYME A ISCLEAVED TO SUCCINATE

Cleavage of the high-energy thioester bond of succinyl CoA provides energy for the substratelevel phosphorylation of GDP to GTP

Enzyme: succinyl-CoA synthetase

Succinyl-CoA


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SUCCINATE IS OXIDIZED TOFUMARATE

2 hydrogens are removed together with their electronsfrom succinate and transferred to FAD, forming FADH 2Enzyme: Succinate dehydrogenase

This is the only enzyme in the TCA cycle found in theinner mitochondrial membrane. All the others are inthe mitochondrial matrix


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FUMARATE GENERATESMALATE

Water adds across the double bond of fumarateto form malateEnzyme: Fumarase


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MALATE IS OXIDIZED REGENERATINGOXALOACETATE

2 hydrogens are removed from the alphacarbon and hydroxyl group of malateNADH is produced

Enzyme: Malate dehydrogenase


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Coenzymes Produced in the CitricAcid Cycle

1. Citrate (6C) to -ketoglutarate (5C) + CO 2

2. -ketoglutarate (5C) to succinate (4C) +CO 2. GDP picks up P i.

3. Succinate to fumarate

4. Malate to oxaloacetate

Total: 2CO 2 + 3 NADH + 1 FADH 2 + GTP

Coenzymes1 NADH1 NADH1 GTP

1 FADH 2

1 NADH


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A. When 1 acetyl CoA enters the citricacid cycle, the C atoms produce 2CO 2.

B. In 1 cycle, a total of 3 NADH areproduced.

C. In 1 cycle, a total of 1 FADH 2 areproduced

D. In 1 cycle, 1 GTP is produced


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WHEN ATP LEVELS ARE HIGH:1. NADH allosterically inhibitsisocitrate dehydrogenase

2. Isocitrate accumulates and favorsthe accumulation of citrate3. Citrate inhibits citrate synthase

WHEN NADH LEVELS ARE HIGH:1. Oxaloacetate is converted tomalate2. Less Oxaloacetate is available for the citrate synthase reaction


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VITAMINS REQUIRED BY THECITRIC ACID CYCLE

Niacin is utilized for the synthesis of NAD,which is used in the isocitrate dehydrogenase,a -ketoglutarate dehydrogenase, and malate

dehydrogenase reactionsRiboflavin is utilized in the synthesis of FAD,which is used in the succinate dehydrogenase reactionFAD is also required by a -ketoglutaratedehydrogenase and pyruvate dehydrogenase


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VITAMINS REQUIRED BY THECITRIC ACID CYCLE

Four vitamins and lipoic acid areneeded by a -ketoglutaratedehydrogenase:

1. Thiamine pyrophosphate (containsthiamine)

2. Lipoic acid

3. CoASH (contains pantothenic acid)4. FAD (contains riboflavin)5. NAD (contains Niacin)


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SYNTHETIC FUNCTIONS OF THETCA CYCLE

Intermediates of the citric acid cycle areutilized in the fasting state for theproduction of glucoseIn the fed state, CAC intermediatessynthesize amino acids or convert oneamino acid to another


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SYNTHETIC FUNCTIONS OF THETCA CYCLE

Anaplerotic reactions replenishintermediates of the TCA cycle as theyare removed for the synthesis of glucose, fatty acids, amino acids, or other compounds


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Key anapleroticreaction

Pyruvate carboxylase

requires biotin . It isfound in the liver, brain,and adipose tissue, (notin muscle) and isactivated by acetyl-CoA

CAC is amphibolic ,because itsintermediates areused for thesynthesis of other compounds (not justoxidation)


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citric acid presentation