TCA Cycle Rxns

how many reactions are in TCA

8

what is the first reaction of the TCA cycle?

Oxaloacetate is first condensed with acetyl-CoA to form citryl-CoA

Then it is hydrolyzed to produce citrate and CoA

what is the enzyme that catalyzes the first reaction of TCA?

citrate synthase

what reactions are in the first reaction of TCA?

adol condensation followed by hydrolysis

what is the second reaction of the TCA cycle?

aconitase first catalyzes the reversible transformation of citrate to isocitrate via the intermediary formation of the tricarboxylic acid cis-aconitate by dehydration

then the double bond of cis-aconitate is rehydrated to form a more reactive secondary alcohol

what occurs in the third reaction of the TCA cycle?

isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form a-ketoglutarate

what are the steps of the third rxn in the TCA cycle?

isocitrate is oxidized to oxalosuccinate

decarboxylation of oxalosuccinate to form the enol intermediate

enol intermediate is then rearranged to a-ketogluterate

what occurs in reaction 4 of the TCA cycle?

the action of the a-ketoglutarate dehydrogenase complex provides oxidative decarboxylation

a-ketoglutarate is converted to succinyl-CoA and O2

what is the α-ketoglutarate dehydrogenase complex composed of?

NAD+ as the electron acceptor

a-ketoglutarate dehydrogenase

dihydrolipoyl transsuccinylase

dihydrolipoyl dehydrogenase

what occurs in reaction 5 of the TCA cycle?

cleavage of succinyl-CoA is coupled to substrate-level phosphorylation

What is the enzyme of reaction 5 of TCA?

succinyl-CoA synthase (succinate thiokinase)

In reaction 5 of TCA what is reversible?

cleavage of the high-energy thioester bond to form succinate

In reaction 5 of TCA what happens in mammals?

coupled to substrate-level phosphorylation of ADP or GDP

two enzyme forms expressed in many tissues

one for ATP and one for GTP

Which of the following is true about the first five reactions of the TCA cycle?

A 2C unit (acetyl-CoA) is linked to oxaloacetate to make citrate (6C)

What are the three reaction that Oxidate Succinate to Oxalacetate?

Oxidation of a single bond to a double bond

Hydration across th double bond

Oxidation of the resulting alcohol to a ketone

Where will the three reactions of needed for Oxidation of Succinate to Oxaloacetate also be seen in?

Fatty acid breakdown and synthesis

Amino acid breakdown and synthesis

What happens in reaction 6 of TCA?

Through a FAD-dependent oxidation, succinate dehydrogenase will oxidize Succinate to a double bond in Fumarate

In reaction 6 of TCA what key events happen in the catalytic mechanism?

A hydride is removed by FAD and a deprotonation

Is the 6th reaction of TCA exergonic to reduce NAD+?

no

What other process is succinate dehydrognase part of?

Electron Transport Pathway (ETC) in the inner mitochondrial membrane

In reaction 6 of TCA the electrons are transferred

from succinate to FAD to form FADH2 and are passed directly to ubiquinone (UQ) in the ETC

In reaction 6 of TCA what type of bond is between FAD and Succinate Dehydrogenase?

Covalent

The covalent bond between FAD and Succinate Dehydrogenase links

C-8a carbon of FAD and the N-3 of a His residue of the enzyme

Ribofavin (B2) is required for the synthesis of

FAD and FMN

Where is FAD and FMN found in

tightly bound prostetic groups in flavoenzymes

The Flavin Coenzymes - FAD/FADH2 can exist in any

of the three oxidation states

What are flavin coenzymes able to be because they can exist in any of the three oxidation states?

Participate in one or two-electron transfer reactions

Flavorproteins are able to

Catalyze many reactions in biological systems

Work with many electron doners and acceptors

What are the three types of Fe-S centers Succinate Dehydrogenase contains?

4Fe-4S

3Fe-4S

2Fe-2S

Where do Iron-Sulfer clusters typically cycle?

Between net oxidation states that differ by 1

Iron-Sulfur clusters can participate in what reactions?

One electron redox reactions (Fe2+ and Fe3+)

Succinate Dehydrogenase (SDH) are bound where?

Inner membrane of the mitochondrion

In reaction 6 of where do the electrons from FADH2 enter into?

The ETC via Fe-S clusters

In reaction 6 of TCA what do the electrons from FADH2 do after entering ETC?

Contribute to ATP synthesis

Distance of redox centers in proteins are optimized to

facilitate electron transfer

Multiple redox centers constitute an

electron wire

What type of reaction is assembly of iron-sulfur clusters into proteins?

enzyme-catalyzed reaction

Friedreich’s ataxia

Inhertied disorder that causes progressive damage to nervous system, gair disturbance, speech problems, heart disease

What is Friedreich’s ataxia due to?

Mutation in gene encoding frataxin

What does Frataxin do?

Participate in assembly and maintenance of Fe-S clusters in mitochondrial enzymes

What enzyme does frataxin focus on and why?

Aconitase

The Fe-S cluster is unstable and sensitive to oxidative loss of iron

In reaction 2 of TCA what is a poor substrate for oxidation?

Citrate

In reaction 2 of TCA how does aconitase change the sterochemistry?

By removing the pro-R of the pro-R arm of citrate

Aconitase constains a

4Fe-4S cluster that’s bound to the protein by the side chains of three cyestine residues

In reaction 2 of TCA what activates Aconitase?

The binding of Fe2+ to the vacant position of the cluster

In reaction 2 of TCA what does the added iron atom do (mechanism)?

Coordinates the C3 carboxyl and hydroxyl groups of citrate and acts as a Lewis acid

Accepts an elecron pair from -OH groups making it a better leaving group I

What happens in reaction 7 of TCA?

Fumarase catalyzes the trans-Hydration of Fumarate to Form L-Malate

In reaction 7 of TCA where does hydration occur?

Across double bond

In reaction 7 of TCA hydration involves

Trans-addition of the water across the double bond

In reaction 7 of TCA what are the 2 possible mechanisms of Fumarase?

Carbonium ion

Cabanion

What happens in reaction 8 of TCA?

Through a NAD+ dependent oxidation, Malate dehydrogenase oxidizes L-Malate to Oxaloacetate

In reaction 8 of TCA what happens to the carbon that gets oxidized?

It recives the -OH group in the previous reaction

Reaction 8 of TCA is expensive but pulled forward by

Favorable citrate synthase reaction

What is Phase 1 and Phase 2 of TCA respectively?

Phosphorylation of glucose and conversion to two molecules if glyceraldehyde 3-phosphate; 2 ATP are used to prime these reactions

Conversion of glyceraldehyde 3-phosphate to pyruvate and the coupled formation of 4 ATP and 2 NADH