Cellular respiration is how every living thing on earth creates energy, from the most basic

single celled organisms to human beings. Without this process humans could have never existed.

Overall, cellular respiration is a set of metabolic reactions that take place in the mitochondria of

cells to convert the energy found in nutrients to a usable form of energy called adenosine

triphosphate (ATP). Any form of nutrient can be used, but glucose is the most common example

and the easiest to understand. There are four main steps of cellular respiration: Glycolysis,

pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation.

In glycolysis, glucose, a six-carbon sugar, is broken down into two molecules of a three-

carbon sugar called pyruvate. To begin this step, a phosphate group from ATP is added to the

glucose ring to create glucose-6-phosphate (G6P) and the ATP becomes adenosine diphosphate

(ADP)1. This ring is then converted to a fructose-6-phosphate (F6P) with help from an enzyme

(Figure 1). Another ATP is used to add an additional phosphate group to the F6P to make it into

a fructose-1,6-bisphosphate (FBP)1. This molecule is then split into two three-carbon sugars

called glyceraldehyde-3-

phosphate (GAP)1. GAP is

oxidized by nicotinamide

adenine dinucleotide

(NAD), so the NAD

removes a hydrogen from

the GAP and turns into

Figure 1. A visual summary of the process of glycolysis. Phosphate groups are in red, and the enzymes
used in each step is in blue.
NADH and 1,3-

bisphoglycerate respectively1. Another enzyme transfers a phosphate group from 1,3-

bisphoglycerate to ADP to make ATP and 3-phosphoglycerate. Since there were two 1,3-
bisphoglycerates, there are also two new ATPs. The 3-phosphoglycerate becomes 2-

phosphoglycerate by relocating the phosphate, and then an enzyme converts the two

phosphoglycerates into phosphoenolpyruvates (PEP) by removing a water group1. Yet another

enzyme transfers a phosphate from the PEPs to two other ADPs, making an additional two ATPs

and pyruvate. Glycolysis in total produces two molecules of pyruvate and four ATPs.

Pyruvate oxidation starts directly after glycolysis ends. The two pyruvate molecules are

reacted with an enzyme that removes a carboxyl group, which is then released as carbon dioxide.

The remaining two-carbon molecules are oxidized and the electrons are accepted by NAD to

form two NADHs. The oxidized two-carbon molecule, known as an acetyl group, is attached to

Coenzyme A to form acetyl CoA.

The citric acid cycle begins with acetyl CoA attaching to a four-carbon acceptor molecule

called oxaloacetate to form a six-carbon chain named citrate1. Citrate rearranges and releases two

of its carbons as carbon dioxide molecules, producing two NADHs. The enzymes that control

this reaction are key regulators of cellular metabolism, and can speed up or slow down the citric

acid cycle depending on the needs of the cell. The remaining four-carbon molecule picks up

Coenzyme A forming succinyl CoA which is very unstable. It quickly replaces the CoA with a

phosphate group1. That phosphate group is then transferred to ADP to make ATP, and the

remaining four-carbon molecule is referred to as succinate. Succinate is then oxidized making

fumarate and two electrons which attach to flavin adenine dinucleotide (FAD) making FADH2

and go directly into the electron transport chain1. Water is then added to fumarate converting it

into a different four-carbon molecule called malate1. The last step of the citric acid cycle is

regenerating oxaloacetate, the starting material, by removing an electron from malate and
 reducing another molecule of NAD to NADH1. At the end of the citric acid cycle the important

products are three molecules of NADH, one molecule of FADH2, the starting material

oxaloacetate, and one molecule of

ATP.

Oxidative phosphorylation

creates the most energy of all the

steps in cellular respiration and it

uses the NADH and FADH2 that

was produced by the other

processes. It starts by having

NADHs transfer their electrons to

the beginning of the electron

transport chain, a series of

proteins found in the inner

membrane of mitochondria.

Electrons are passed from one

member of the transport chain to

Figure 2. A visual explanation of the process of the citric acid cycle. The number of
another in a series of redox
carbons in each molecule are represented by the Cs in grey circles
reactions. The energy released

from this is used to create a proton gradient between outside and inside the mitochondria. As

protons move down the gradient, they pass through an enzyme called ATP-synthase which

harnesses their energy to synthesize around 25-29 ATP per starting molecule of glucose1.
 Overall, the process of cellular respiration produces 30-32 molecules of ATP per

molecule of glucose. That is a high estimate though, and the actual number varies from source to

source. It is an extremely important process for any living thing, and it is the starting point for

numerous other metabolic pathways in the cell.

 Sources

1. Alberts, B. (2014). Essential cell biology (3rd ed.). New York: Garland Science.