Citric Acid Cycle

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  • Created by: LBCW0502
  • Created on: 17-12-17 18:38
What is the citric acid cycle also known as?
Tricarboxylic acid (TCA) cycle or the Krebs cycle
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Describe the reaction of oxidative decarboxylation
Pyruvate is oxidised to acetyl CoA (activated acetate). Catalysed by pyruvate dehydrogenase complex. CO2 produced. Irreversible reaction. NAD is reduced. Exergonic
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Describe how NAD becomes reduced
When NADH is formed, a hydride ion (H-) is released to respiratory chain (lost in solvent), carries two electrons to oxygen (nitrate of sulfate in anaerobic organisms). Transfer of electrons from NADH generates 2.5 ATP molecules/pair of electrons
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Why is the pyruvate dehydrogenase complex irreversible?
Unable to reattach carbon dioxide to acetyl CoA to produce carboxyl labelled pyruvate
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How many coenzymes does the pyruvate dehydrogenase complex require?
Five coenzymes/prosthetic groups
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What are the coenzymes required in the PDH complex?
Thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), coenzyme A (CoA-SH), nicotinamide adenine dinucleotide (NAD), and lipoate (vitamins - thiamine in TPP, riboflavin in FAD, niacin in NAD and panthothenate in CoA)
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What are thioesters?
Acyl groups covalently linked to the thiol group (high free energy, high acyl group transfer potential/donation acyl group to acceptor molecules
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Describe features of lipoate
Has two thiol groups that can undergo reversible oxidation to a disulfide bond. Able to act as both electron H carrier and acyl carrier
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The PDH complex consists of which distinct enzymes?
Pyruvate dehydrogenase, dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase (each present in multiple copies/varies among species)
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What is the function of E1?
Decarboxylation of pyruvate (produce hydroxyethyl-TPP). Oxidation of hydroxyethyl group to acetyl group. Electrons from oxidisation reduce disulfide of lipoate bound to E2, acetyl group transferred to thioester linkage/one SH group of reduced lipoate
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What is the function of E2?
Catalyse transfer of acetyl group to CoA to form acetyl CoA
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What is the function of E3?
Catalyse regeneration of disulfide (oxidised) form of lipoate. Electrons pass first to FAD then to NAD+
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What is the component which tethers intermediates to the enzyme complex to allow substrate channeling?
The long lipoyllysine arm - swings from active site of E1 to E2 to E3
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Does the PDH complex appear similar in terms of organisation to enzymes complexes that catalyse the oxidation of alpha-ketoglutarate and branched-chain alpha-keto acids?
Yes
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How many steps are there in the citric acid cycle?
Eight steps
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Describe the first step in the TCA cycle
Condensation of acetyl CoA with oxaloacetate to form citrate. Catalysed by citrate synthase. Exergonic. Negative free energy
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Describe the structure of the enzyme used in step 1 of the TCA cycle
Each subunit of the homodimeric enzyme is a single polypeptide with two domains, one large and rigid and the other smaller and more flexible with active site between them
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Describe the enzyme action in step 1 of the TCA cycle (1)
Oxaloacetate (first substrate) binds to enzyme and induces a large conformational change in flexible domain, creating a binding site for acetyl CoA (second substrate)
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Describe the enzyme action in step 1 of the TCA cycle (2)
When citroyl CoA has formed in the enzyme active site, another conformational change brings about thioester hydrolysis, releasing CoA-SH (induced fit, condensation reaction)
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Describe the second step in the TCA cycle
Aconitase (hydratase) catalyses the reversible transformation of citrate to isocitrate through the tricarboxylic acid cis-aconitate intermediate (doesn't dissociate from active site). Endergonic (iron sulfur centre in enzyme/substrate/water)
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Describe the third step in the TCA cycle
Isocitrate dehydrogenase catalyses oxidative carboxylation of isocitrate to form alpha-ketoglutarate (Mn 2+ interacts with intermediate)
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Describe the fourth step in the TCA cycle
Alpha-ketoglutarate is converted to succinyl CoA and CO2 by alpha-ketoglutarate dehydrogenase complex (use of NAD and CoA). Thioester bond formed. Exergonic (application to PDH complex)
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Describe the fifth step in the TCA cycle
Succinyl CoA (thioester bond/negative free energy). Energy released to break bond. Synthesis phosphoanyhydride bond in GTP/ATP. Succinate formed. Exergonic. Enzyme used is succinyl CoA synthetase/succinic thiokinase
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What is the function of nucleoside diphosphate kinase?
Catalyse the reaction between GTP and ADP (formation of GDP and ATP), no free energy
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Describe the sixth step in the TCA cycle
Succinate is oxidised to fumarate by succinate dehydrogenase (flavoprotein). No free energy
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Describe the seventh step in the TCA cycle
The reversible hydration of fumarate to L-malate is catalysed by fumarase (fumarate hydratase). Exergonic. Enzyme is stereospecific (prefers trans)
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Describe the eighth step in the TCA cycle
NAD linked L-malate dehydrogenase catalyses the oxidation of L-malate to oxaloacetate. Endergonic
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Other cards in this set

Card 2

Front

Describe the reaction of oxidative decarboxylation

Back

Pyruvate is oxidised to acetyl CoA (activated acetate). Catalysed by pyruvate dehydrogenase complex. CO2 produced. Irreversible reaction. NAD is reduced. Exergonic

Card 3

Front

Describe how NAD becomes reduced

Back

Preview of the front of card 3

Card 4

Front

Why is the pyruvate dehydrogenase complex irreversible?

Back

Preview of the front of card 4

Card 5

Front

How many coenzymes does the pyruvate dehydrogenase complex require?

Back

Preview of the front of card 5
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