TCA Cycle

TCA Cycle Formula

Reaction 1 TCA

Citrate Synthase (transferase)

Condensation of OAA and acetyl-CoA

Low [OAA] in mitochondria

Thioester hydrolysis drives the reaction forward

Reaction 2 TCA

Aconitase (Lyase)

Reversible: At equilibrium: 90% citrate, 4% cis-aconitate, 6% isocitrate

The next reaction is exergonic, pushing this reaction forward

Reaction 3 TCA

isocitrate dehydrogenase (oxidoreductase)

Oxidation to oxalosuccinate.

β-decarboxylation to α-ΚG.

Exergonic. Pushes the aconitase reaction forward.

The B-keto group acts as an electron sink to stabilize the carbanion transition state

Reaction 4 TCA

α-Ketoglutarate dehydrogenase complex (oxidoreductase)
Decarboxylates to oxidize the carbon and reduce NAD+

α-ketoglutarate is an α-keto acid, so it is difficult to stabilize the carbanion to decarboxylate. Covalent linkage to TPP to stabilize the carbocation
-Uses same 5 cofactors as pyruvate dehydrogenase complex

Reaction 5 TCA

Succinyl-CoA synthetase (ligase)

1) Phosphate displaces CoA, retaining the energy of the high energy thioester

2) The phosphate is transferred to a His on the enzyme

3) The phosphate is transferred to: ADP in brain, muscle for metabolism or - GDP – kidney and liver for biosynthesis

Reaction 6 TCA

Succinate dehydrogenase (oxidoreductase)

Electrons transported to FAD then Q (quinone, another electron acceptor).

FAD is used because it’s a stronger oxidant than NAD+, and it is more difficult to oxidize the C—C bond than a C—O •

The enzyme is in the inner mitochonodrial membrane, and is called Complex II in the Electron Transport Chain.

Reaction 7 TCA

Fumarase or Fumarate Dehydratase (lyase)

Fumarate is symmetrical. Trans addition of water stereospecifically generates L-malate

Similar to the second step of Aconitase, adding H2O across the double bond.

Reaction 8 TCA

Malate dehydrogenase (oxidoreductase)

Reaction is very endergonic. It’s pushed forward because step 1 is very exergonic • Oxaloacetate is very low, < 10-6 M

Autotrophs

energy from inorganic compounds

plants - CO2 using the protein RuBisCo

5 other Carbon fixation pathways in bacteria and archaea-

reductive acetyl-CoA pathway – synthesizes acetyl-CoA from 2 CO2

-one of the oldest pathways

Reductive Citric Acid Cycle (rTCA)- reverse of the TCA cycle, is anabolic

3 other cycles

reverse TCA

Anabolic

Uses electrons from reduced NADPH, FADH to reduce oxaloacetate

Photoautotrophs

Sunlight and carbon reduction

Chemoautotrophs

chemical oxidation of inorganic molecules

Heterotrophs

energy from organic compounds

Photoheterotrophs

photosynthetic organisms (typically bacteria) that capture light as energy for organic carbon oxidation (not reducing)

Chemoheterotrophs

Ultimate source of energy is chemical oxidation of organic molecules

-Humans, animals, fungi, most protists, many bacteria