TCA Cycle

Synthesis of Acetyl CoA

1. pyruvate dehydrogenase catalyzes decarboxylation of pyruvate

2. dihydrolipoyl transacetylase catalyzes transfer of acetyl group to CoA

3. dihydrolipoyl dehydrogenase catalyzes regeneration of oxidized form of lipamide

pyruvate dehydrogenase complex

in mitochondrial matrix, pyruvate is oxidatively decarboxylated by pyruvate dehyrogenase to form acetyl coA

Four general Stages of TCA cycle

1. Oxidation

2. Electron Transfer

3. Energy output

4. electron transfer

Flaving adenine dinucleotide

a second electron acceptor involved in the TCA cycle

TCA cycle step one

a proton is removed from CH3 group on acetyl coA, charge CH2- group forms bond to carbonyl carbon of oxaloacetate, loss of coA drives reaction forward

oxaloacetate + acetyl coA → citrate

Citrate Synthase

enzyme that catalyzes step one of TCA cycle

TCA cycle step two

isomerization where water is removed and added back moving hydroxyl group from one carbon to its adjacent carbon

citrate → isocitrate

aconitase

enzyme that catalyzes TCA cycle step two

TCA cycle step three

change of the C carrying the O group to a carbonyl group, immediate product is unstable so a CO2 atom is lost

isocitrate → a-ketoglutarate + CO2 + NADH

Isocitrate dehydrogenase

enzyme that catalyzes TCA cycle step three

TCA cycle Step four

oxidation of the product to produce NADH, CO2 and a high energy thioester bond to CoA

a-ketoglutarate → succinyl coA + CO2 + NADH

a-ketoglutarate dehydrogenase complex

enzyme that catalyzes step four of TCA cycle

TCA cycle Step five

displacement of coA by a phosphate molecule forming high energy phosphate linkage to succinate. Phosphate is passed to GDP to form GTP which is passed to ADP to form ATP

succinyl coA → succinate + ATP

succinyl-coA synthetase

enzyme that catalyzes step five of TCA cycle

TCA Cycle Step six

oxidation of succinate moving two Hydrogen atoms to FAD

succinate → fumarate + FADH2

succinate dehydrogenase

enzyme that catalyzes step six of TCA cycle

TCA cycle step seven

addition of water to fumarate, placing a hydroxyl group next to carbonyl carbon

fumarate → malate

fumarase

enzyme that catalyzes step seven of TCA cycle

TCA cycle step eight

converts C with OH group do carbonyl group and reduces NAD+ to NADH and reforming oxaloacetate for cycle to repeat

malate → oxaloacetetate + NADH

malate dehydrogenase

enzyme that catalyzes step eight of TCA cycle

Net Products of TCA cycle for one glucose (cycle runs twice)

4 CO2, 6NADH, 2FADH2, 2ATP\

Regulation of pyruvate dehydrogenase complex

the enzyme can be phosphorylated to make it inactive 

if there is low energy PDH will be activated, if there is high energy it will be inactivated

Regulation of TCA Cycle

regulated at three points:

1. before pyruvate is fixed to acetyl coA, negatively regulated by, ATP, acetyl coA and NADH, positively by ADP and pyruvate

2. during step 3, negatively regulated by ATP and NADH, positively by ADP

3. during step four, negatively regulated by ATP, succinyl coA and NADH