The citric acid cycle is a series of chemical
reactions that takes place in the mitochondrial matrix.
This cycle uses acetyl CoA
derived from sugar and fat breakdown
to form ATP, NADH, FADH2, and carbon dioxide.
The NADH and FADH2
can be used to form additional ATP
through the electron transport chain.
The citric acid cycle goes by many names
including the tricarboxylic acid (or TCA) cycle
and the Krebs cycle.
Citric acid refers to the citrate that is produced in the first step of the pathway.
The tricarboxylic acid title gets its name
from the three carbon dioxides that are produced
for each fully oxidized pyruvate.
Krebs refers to Hans Adolf Krebs
who identified the full cycle in 1937.
He was eventually awarded the Nobel Prize for
Physiology or Medicine in 1953 for his discovery.
In the first step of the cycle,
an enzyme called citrate synthase
joins the two-carbon acetyl group from acetyl CoA
with the four-carbon oxaloacetate
to form a six-carbon citrate.
In step two, an enzyme called aconitase
converts citrate into isocitrate.
Next, an isocitrate dehydrogenase enzyme
oxidizes isocitrate, a six-carbon molecule,
to a five-carbon α-ketoglutarate.
The carbon that was lost is released as carbon dioxide
and one NADH is also formed.
The carbon dioxide that is released
was originally part of oxaloacetate
and not acetyl CoA.
In the fouth step,
an enzyme called α-ketoglutarate dehydrogenase
converts α-ketoglutarate
into a four-carbon succinyl CoA.
Similar to step three,
this reaction produces one carbon dioxide
and one NADH.
In step five,
a succinyl CoA synthetase enzyme
converts succinyl CoA into succinate.
This produces GTP which is converted to ATP.
In step six,
an enzyme called succinate dehydrogenase
converts succinate into fumarate.
This step makes one FADH2.
In step seven, a fumarate hydratase enzyme
then converts fumarate into malate.
In the final step of the citric acid cycle,
a malate dehydrogenase enzyme
converts malate back to oxaloacetate.
Like all steps involving a dehydrogenase,
a coenzyme is produced.
Here it is NADH.
The oxaloacetate that was regenerated through the citric acid cycle
is now ready to join with another acetyl group
and begin the cycle a second time.
For every one glucose that is broken down through glycolysis,
two pyruvates will be produced.
These two pyruvates will produce two acetyl CoAs.
So, for every one glucose,
two acetyl CoAs will be made
and two turns of the citric acid cycle will occur.
This means each product of the cycle must be doubled.
A total of four CO2,
six NADH,
two FADH2, and two ATPs are made
through the citric acid cycle.
NADH and FADH2 are electron carriers
that can produce more ATPs later in aerobic respiration.
In addition to sugars like glucose,
proteins and fats can also provide carbon substrates to fuel the citric acid cycle.
Proteins can be broken down into individual amino acids
such as alanine, aspartate, and glutamate
and converted into intermediates in the cycle.
Fatty acids can be broken down into acetyl CoA
which then begins the citric acid cycle.
This metabolism of sugars, proteins, and fats
through the citric acid cycle
provides the vital energy necessary to maintain many cellular processes.