SPEAKER: The origin of energy production and biosynthesis
inside your living cells is the dynamic mitochondria organelle.
Mitochondria are filled with metabolic enzymes that
catalyze a loop of chemical reactions
called the citric acid cycle.
The eight steps of the citric acid cycle
gradually break apart two carbon atoms from glycolysis,
capturing liberated electrons for the electron transport
chain, while generating carbon dioxide as waste.
The citric acid cycle starts with the end product
of a previous cycle, the four carbon molecule oxaloacetate.
New carbon enters from glycolysis
in the form of acetyl CoA, a two carbon acetyl
group attached to coenzyme A.
Step 1 is the catalytic transfer of a two carbon acetyl
group from coenzyme A to four carbon oxaloacetate,
creating six carbon citric acid, the molecule that
gives the cycle its name.
Citric acid is used by your cells
for the biosynthesis of fatty acids, lipids, and cholesterol,
and is also the substrate for step 2 of the citric acid
cycle.
The enzyme reaction of step 2 makes a small change
to the citric acid molecule, moving
the position of an oxygen atom, converting citrate
into isocitrate.
Step 3 of this cycle removes the carbon atom,
forming carbon dioxide as waste, while converting six carbon
isocitrate to five carbon ketoglutarate.
During this process, chemical energy
is harvested when two electrons are transferred
to coenzyme NADH, which delivers them
to nearby enzymes of the electron transport chain.
Step 4 of the citric acid cycle is
performed by a huge multi-enzyme complex,
connecting multiple chemical reactions
with flexible tethers, efficiently
moving reactants between active sites
and diverting electrons between pathways.
The large complex is made with a repeating unit of three core
enzymes working in sequence to remove a carbon
atom from ketoglutarate, generating carbon dioxide
waste, then attaching four carbon succinyl to coenzyme A.
The electron from ketoglutarate oxidation
is retained by the tethered enzyme
before passing it to coenzyme NADH, which delivers electrons
to the electron transport chain.
Enzymes of step 5 separate succinyl from coenzyme A
by breaking an energetic bond, providing enough energy
to create GTP.
GTP is a building block of RNA and an energy source
for protein synthesis.
In the most direct path to ATP from the citric acid cycle,
other enzymes in the matrix can use GTP
to make the chemical fuel ATP.
Step 6 is performed by an enzyme embedded
in the inner mitochondrial membrane.
This enzyme is also known as complex two of the electron
transport chain.
The enzyme catalyzes the oxidation of succinate
to create fumarate, releasing two electrons
that hop through the interior to coenzyme Q, which is reduced.
Coenzyme Q travels in the membrane carrying the electrons
to nearby enzymes of the electron transport chain.
Step 7 takes fumarate generated by step 6
and reacts it with water to create four carbon malate.
The final step of the citric acid cycle
uses malate to regenerate oxaloacetate,
transferring electrons to coenzyme NADH, which supplies
the electron transport chain.
Oxaloacetate can return to step 1 for another loop of the cycle
and is also an essential building
block for making amino acids and the genetic code of DNA
and RNA.
At the center of cellular metabolism,
the citric acid cycle generates both chemical energy
and material for biosynthesis of the entire diversity
of molecules found inside a living cell.