November 17, 2015

TCA

After glycolysis NADH is reoxidized to NAD+

this occurs through oxidative phosphorylation
o This process can be called respiration
When metabolic processes for ATP production in
o

which inorganic molecules function as electron

acceptors
The inorganic acceptor for humans is Oxygen
Anaerobic respiration uses something else besides

oxygen (bacteria do this often)

Using nitrate (E. Coli)
o Oxidation of pyruvate per molecule of glucose has a net
yield of over 30 ATP
o Pyruvate
Product of glycolysis
In the first step it loses its carboxyl group and
becomes Acetyl-CoA
Oxidative decarboxylation
o Acetyl-CoA
Used to make Citrate
o Citrate
Isomerization occurs along with oxidative
decarboxylation
o Only substrate level phosphorylation is after Succinyl-CoA
Converts GDP to GTP (equivalent to ATP)
o Net 2 CO2 3 NADH 1 ATP 1 FADH2
o Why is it called Krebs Cycle
MD/Biochemist
In 1930 he escaped to England during WWII
Awarded Nobel prize
He was the one to convince others that this was a
cycle and not a linear biochemical pathway
o Vitamin B3 is needed in our diet to synthesize CoA
o CoA enzymatic activity is centered around the thiol on the
end
o Thiamine

Required by Vitamin B1 in order to synthesize TPP

Deficiency cause Berry Berry
o Pyruvate conversion to Acetyl-CoA
Done through Pyruvate dehydrogenase complex
Comprised by 3 enzymes in a 4 step process
Why 3?
o The lipoic acid has to visit the active sites

of all three enzymes

Via the swinging arm mechanism that
lipoamide has

Citrate Synthesis
The synthesis from Acetyl-CoA to citrate is

irreversible
When NADH is high the TCA will slow down
Citrate Synthase catalyzes this reaction
o Isocitrate
Isomerization occurs
Catalyzes by Aconitase
Enzyme extracts water from citrate to leave an

intermediate
Then adds water back
This enzyme contains an Iron-Sulfur cluster
This rearrangement is necessary for the following

reaction
o Fluoroacetate is extremely toxic, which acts on the TCA
cycle (also used as rat poison)
The substrate itself isnt the toxic part, the substrate
it gets converted into is toxic
o Ketoglutarate
Isocitrate dehydrogenase oxidizes the isocitrate and
then a decarboxylation occurs
o Succinyl-CoA
Ketoglutarate is oxidative decarboxylated
CO2 is lost
This is multi subunit complex
o Fumerate
Oxidation of succinate

FAD

Weak reducing agent

This is coupled with a reduction of FAD to FADH2
o FADH2 remains bound to the enzyme
o Covalently bound
o Must reoxidize to continue this reaction
This enzyme is associated with the membrane of
the mitochondria

Has 3 redox states

Can participate in one or two redox reactions
Contains 3 iron-sulfur clusters
Provides a path through the enzyme in which
electrons move

11/19/15

TCA
o
o

FAD
Used to transport electrons through the iron clusters
L-Malate
Fumerate is hydrolyzed with water with Fumerase to create
L-Malate, similar to Citrate to Isocitrate
Oxaloacetate
Malate Dehydrogenase is used with NAD+ to create
oxaloacetate
Glyoxalate
Used to regulate the amount of carbons used for synthesis
Located in the glyoxysome
Depends on the TCA cycle in the mitochondria