Citric Acid Cycle or Kreb’s Cycle
acetyl-CoA production. But in the case of glucose, after
 It is a series of chemical reactions in the cell that
breaks down food molecules into carbon dioxide,
water, and energy.
 Now to create electricity, electron rich molecules
must deliver electrons to a chain of complexes, →
the electron transport chain, which move them to a
final acceptor, a molecule of oxygen.
Two Electron Donor Molecules:
1. Nicotinamide Adenine Dinucleotide (NADH)
2. Flavin Adenine Dinucleotide (FADH2).
The cell has to produce NADH and FADH2 in the first
place, and they’re produced by critical enzymes called
dehydrogenases.
Dehydrogenases are the main enzymes found in
the citric acid cycle or Kreb’s cycle.
In fact, the citric acid cycle is a set of 8 enzymatic
reactions that start with a molecule called acetyl-CoA,
and four of the enzymes, half of them, are
dehydrogenases.
And in this process, AcetylCoA gets converted into
carbon dioxide. Acetyl-CoA comes from various sources
depending on whether you’ve just eaten or are starving.
Let’s say that you’re hungry and a bit angry → so
you’re feeling hangry. That’s when stress hormones like
glucagon, epinephrine, and cortisol → start to rise. In
this hangry state, fatty acids from triglycerides become
the primary source of acetyl-CoA.
Now, let’s say you have a bowl of delicious SINIGANG
soup, everything changes → insulin is plentiful and you
have plenty of acetyl-CoA from breaking down glucose,
fructose, and galactose → with glucose playing the
biggest role.
Now, alcohol is also a source of Acetyl-CoA in the liver
where it’s metabolized.
In addition, proteins can also help contribute to
a meal, one glucose, a 6-carbon molecule, splits into
two 3 carbon pyruvate molecules through glycolysis,
which occurs in the cytoplasm of the cell.
a. Each of the pyruvate molecules then enter the
mitochondria.
b. In the mitochondria, an enzyme called
PYRUVATE DEHYDROGENASE → snatches a
carbon and two oxygens, from pyruvate, and
adds coenzyme A, making → acetyl-CoA.
c. In the process two electrons are also transferred
to a nearby NAD+, → in the form of a hydride
ion, → making NADH, while the carbon and two
oxygens are released to form carbon dioxide or
CO2.
This step links glycolysis to the citric acid cycle, but
really isn’t considered part of either process.
Yet, it is a source of NADH and CO2 and shares some
similarity with enzymes of the citric acid cycle.
As we go through the citric acid cycle, we’ll keep
track of our total GTP, NADH, FADH2, and CO2 count
with these energy counters.
And remember that this cycle has many
dehydrogenases.
1. Okay, Citric acid cycle starts when acetyl-CoA is
joined to a 4-carbon molecule called
oxaloacetate by an enzyme called CITRATE
SYNTHASE, making a 6-carbon molecule - citrate.
This process also releases coenzyme A.
2. Next, another enzyme, ACONITASE, rearranges
the chemical shape of citrate to make its isomer,
isocitrate, without adding or removing any
carbon molecules.
So far, we haven’t made anything related to energy.
3. But here comes the first dehydrogenase, called
ISOCITRATE DEHYDROGENASE, which removes a
carbon and two oxygens from isocitrate.
4. In the process two electrons are also transferred
to a nearby NAD+, in the form of a hydride ion,
making our first NADH, and the carbon and
oxygens give us our first CO2, leaving us with a 5-
carbon molecule called alpha ketoglutarate.
 High levels of ATP and NADH in the cell can prevents succinyl CoA, turning it into a 4-carbon succinate
isocitrate dehydrogenase, signaling the cycle to slow molecule.
down since the cell has of energy.
It also couples a phosphate and GDP molecule to the
On the other hand, high levels of ADP, an ATP reaction, making GTP.
precursor, stimulate this enzyme, signaling the cycle to
7. Alright, next, the enzyme SUCCINATE
speed up since the cell needs more energy.
DEHYDROGENASE transforms succinate to
In fact, isocitrate dehydrogenase is considered the fumarate.
rate-limiting step of the cycle! 8. In the process two electrons and two protons are
transferred to FAD to produce FADH2.
And you remember that jogging we wanted to do?
Well, calcium levels rise during muscle contraction, and Also, it’s worth knowing that succinate
contraction is work and requires energy. And as it turns dehydrogenase is already part of the electron transport
out - calcium also activates the enzyme isocitrate chain, and it goes by the name Complex II.
dehydrogenase.
9. Next, an enzyme called FUMARATE HYDRASE or
5. Next, another dehydrogenase called ALPHA SIMPLY FUMARASE adds a water molecule to
KETOGLUTARATE DEHYDROGENASE converts fumarate, making malate.
the 5-carbon alpha-ketoglutarate to the 4-carbon
Malate is then converted to oxaloacetate by the
succinyl-CoA, releasing our 2nd molecule of NADH
enzyme MALATE DEHYDROGENASE, making our 3rd and
and CO2 in the process.
final NADH in the process.
Now, this enzyme requires 5 sidekicks called
So now we’ve come full circle, Oxaloacetate can then
COFACTORS to function: You can remember them by
join up with another new acetyl-CoA molecule that’s
the first letters of mnemonic: T-rex Loves and Cares for
just hanging around waiting to begin a new cycle.
Nachos. “T” for thiamine, or vitamin B1. “L” for lipoic
acid. “C” for coenzyme A also called vitamin B5 or The control of the citric acid cycle is based on energy
pantothenate. “F” for FAD+ also called vitamin B2 or level of the cell. It has to run all the time!
riboflavin, and “N” for NAD+ also called vitamin B3 or
niacin. So, when it needs more energy, it speeds up, and
when it has enough energy, it slows down.
 Thiamine/ Vitamin b1
Hormones don’t play a role in its regulation.
 Lipoic Acid
 Coenzyme A/ Vitamin b5/ Pantothenate
 FAD+/ Vitamin B2/ Riboflavin
 NAD+/ Vitamin B3/ Niacin

So adequate intake of these vitamins is essential,

because deficiencies can disrupt the citric acid cycle,
and impact overall health as a consequence.

For example, Thiamine Deficiency can lead to a

disease called Beriberi, in which the central nervous
system and then the heart can’t work properly.

Likewise, Niacin Deficiency can cause a disease called

Pellagra, characterized by 4“D” s: diarrhea, dermatitis,
dementia and, if the deficiency isn’t corrected, it can
cause death.

6. But let’s say that the cycle is working properly,

then the next step is that an enzyme called
SUCCINATE THIOKINASE removes the CoA from