CITRIC ACID CYCLE:
The acetyl CoA that enters the citric cycle is not the one that leaves as CO2.
Pyruvate dehydrogenase and other dehydrogenases are multiprotein complexes-decarboxylate
the carbon chain
using the decarboxylation energy to drive other reactions fwd
enery requiring step: addition of Coenzyme A
Two decarboxylation reactions.--> full oxidation of glucose; 2 C’s leave in form of co2
Mostly energy in form of ATP and NADH, these provide electrons to ETC
The reason that citric cycle can go fwd are the early reactions—they have a very large –ve free
energy, they provide and pull rxns like citrate synthase forward
Citrate synthase reaction is pulled fwrd and has –ve free energy because of the cleavage of the
thioester bond , release of CoA from acetyl-CoA..means citrate cycle is always favourable even
when reactants are limited.
Net actual free energy is neutral –is not taking energy or wasting energy to produce NADH
3 NADH produced /Acetyl-CoA and in pyruvate dehydrogenase rxn.
2.5 ATP/1NADH MOLECULE
FADH2- is a bound prosthetic,it can’t leave the enzyme, therefore, it must give up its electrons
to regenerate FAD ,usually it gives its electrons to NADH in a soluble protein i.e pyruvate
dehydrogenase…in membrane bound, it gives it to Coenzyme Q i.e in ETC because NADH is
not associated with membrane.
The only thing tht crosses inner mitochondrial membrane is water (through porins).membrane
has to have a specific transporter for anything that has to cross.the transporter is based on
concn gradient and are selective and DONOT require energy..but they are selective and
Porins are also for intermediates of citric acid cycles like malate—malate transporter
there is also a specific transporter for citrate. they tend to be unidirectional. if citrate is
high and excess of citric cycle metabolites, more citrate is produced and high concn
inside mitochondria means it spills outside of mitochondria, it regulates fatty acid
synthesis—citrate spilling out into cytoplasm is a signal that too much energy is being
produced, citrate is cleaved in to form acetyl-coa in the cytoplasm and aceyl-
coa(opposite rxn) can go fatty acid production oxaloacetate can go to MAYBE
gluconeogenesis.but more likely in to malte and back into mitochondria. The transporter
is a way to get cytosolic NADH in to the mitochondria. rmbr NADH can’t cross
mitochondria either.there isn’t a NADH transporter.therefore, electrons are transported
inform of malate
when sugars are high, high pyruvate generated, high concn of citrate which spills out
and more than cell need way to balance energy metabolism and storage.
Is not as strongly regulated as glycolysis.
Regulation more allosteric
1.High amounts of acetyl CoA regulates pyruvate dehydrogenase, -ve feedback—
high acetyl CoA, decreased production of AcetylCoA
2.Citrate!!-another imp regulator, spilling –main way of communication inside of
mitcohondria with cytoplasm. Stimulates energy storage and fatty acid production
and inhibits energy production or metabolism. Inhibits PFK1 of glycolysis and
slows down glycolysis.
3.Calcium-high in mitochondria when cellular activity is high. When u have cell
signaling i.e calcium is coming in..but want to be tightly regulated..and doesn’t
deviate and want localized increased and transient. If Ca is increased,
mitochondria removes it very fast.
4.ADP is exchanged with ATP-ATP Synthase synthesizes ATP. If more energy
consumption,more ADP come inside mitochondria. Transporter exchanges ATP
There is no phosphorylation event within TCA cycle. Some covalent modification of
pyruvate dehyrdogenase i.e kinase that phosphorylates and inactivates pyruvate
dehydrogenase and dephosphorylates. Its all allosteric.
The acetyl coa that enters the citric cycle is not the one that leaves as co2. Pyruvate dehydrogenase and other dehydrogenases are multiprotein complexes-decarboxylate the carbon chain using the decarboxylation energy to drive other reactions fwd enery requiring step: addition of coenzyme a. Two decarboxylation reactions. --> full oxidation of glucose; 2 c"s leave in form of co2. Mostly energy in form of atp and nadh, these provide electrons to etc. The reason that citric cycle can go fwd are the early reactions they have a very large ve free energy, they provide and pull rxns like citrate synthase forward. Citrate synthase reaction is pulled fwrd and has ve free energy because of the cleavage of the thioester bond , release of coa from acetyl-coameans citrate cycle is always favourable even when reactants are limited. Net actual free energy is neutral is not taking energy or wasting energy to produce nadh. 3 nadh produced /acetyl-coa and in pyruvate dehydrogenase rxn.