Cellular respiration is a series of chemical reactions that break down glucose to produce ATP, which may be used as energy to power many reactions throughout the body.
There are three main steps of cellular respiration: glycolysis, the citric acid cycle, and oxidative phosphorylation. Glycolysis takes place in the cytosol, the citric acid cycle occurs in the mitochondrial matrix, and oxidative phosphorylation occurs on the inner mitochondrial membrane.
The starting reactants of cellular respiration include glucose, ATP, and NAD+; and the final products include ATP and H2O.
The rate-determining enzymes for cellular respiration include phosphofructokinase-1, pyruvate dehydrogenase, and isocitrate dehydrogenase.
Diseases that affect cellular respiration typically disrupt one or more enzymes involved in the process, such as pyruvate kinase or succinyl-CoA-synthase.
Role of mitochondria in Cellular Respiration?
One objective of the degradation of foodstuffs is to convert the energy contained in chemical bonds into the energy-rich compound adenosine triphosphate (ATP), which captures the chemical energy obtained from the breakdown of food molecules and releases it to fuel other cellular processes.
In eukaryotic cells (that is, any cells or organisms that possess a clearly defined nucleus and membrane-bound organelles) the enzymes that catalyze the individual steps involved in respiration and energy conservation are located in highly organized rod-shaped compartments called mitochondria.
In microorganisms the enzymes occur as components of the cell membrane. A liver cell has about 1,000 mitochondria; large egg cells of some vertebrates have up to 200,000.
Steps of cellular respiration
During cellular respiration, a glucose molecule is gradually broken down into carbon dioxide and water. Along the way, some ATP is produced directly in the reactions that transform glucose. Much more ATP, however, is produced later in a process called oxidative phosphorylation.
Oxidative phosphorylation is powered by the movement of electrons through the electron transport chain, a series of proteins embedded in the inner membrane of the mitochondrion.
These electrons come originally from glucose and are shuttled to the electron transport chain by electron carriers NAD+ and FAD, which become NADH and FADH2 when they gain electrons. The molecule isn’t appearing from scratch, it’s just being converted to its electron-carrying form:
NAD+ + 2e– + 2H+ → NADH + H+
FAD + 2e– + 2H+ → FADH2
To see how a glucose molecule is converted into carbon dioxide and how its energy is harvested as ATP and NADH/FADH2 in one of your body’s cells, let’s walk step by step through the four stages of cellular respiration.
1. Glycolysis.
In glycolysis, glucose a six-carbon sugar undergoes a series of chemical transformations. In the end, it gets converted into two molecules of pyruvate, a three-carbon organic molecule. In these reactions, ATP is made, and NAD+ is converted to NADH.
2. Pyruvate oxidation.
Each pyruvate from glycolysis goes into the mitochondrial matrix the innermost compartment of mitochondria. There, it’s converted into a two-carbon molecule bound to Coenzyme A, known as acetyl CoA. Carbon dioxide is released and NADH is generated.
3. Citric acid cycle.
The acetyl CoA made in the last step combines with a four-carbon molecule and goes through a cycle of reactions, ultimately regenerating the four-carbon starting molecule. ATP, NADH and FADH2 are produced, and carbon dioxide is released.
4. Oxidative phosphorylation.
The NADH and FADH2 made in other steps deposit their electrons in the electron transport chain, turning back into their “empty” forms (NAD+ and FAD).
As electrons move down the chain, energy is released and used to pump protons out of the matrix, forming a gradient.
Protons flow back into the matrix through an enzyme called ATP synthase, making ATP. At the end of the electron transport chain, oxygen accepts electrons and takes up protons to form water.
Glycolysis can take place without oxygen in a process called fermentation. The other three stages of cellular respiration pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation require oxygen in order to occur. Only oxidative phosphorylation uses oxygen directly, but the other two stages can’t run without oxidative phosphorylation.
Each stage of cellular respiration is covered in more detail in other articles and videos on the site. Try watching the overview video, or jump straight to an article on a particular stage by using the links above.
Common mistakes and misconceptions
Anaerobic respiration is a normal part of cellular respiration.
Glycolysis, which is the first step in all types of cellular respiration is anaerobic and does not require oxygen. If oxygen is present, the pathway will continue on to the Krebs cycle and oxidative phosphorylation. However, if oxygen is not present, some organisms can undergo fermentation to continually produce ATP.
Plants undergo cellular respiration.
Many people believe that plants undergo photosynthesis and animals undergo respiration. Really, plants do both! Plants simply undergo photosynthesis first as a way to make glucose. Animals don’t need to photosynthesize since they get their glucose from the food they eat.
Cellular respiration is not simply the same as “breathing.”
This can be confusing! People often use the word “respiration” to refer to the process of inhaling and exhaling. However, this is physiological respiration, not cellular respiration. The two are related processes, but they are not the same.
What diseases can affect cellular respiration?
Several diseases can affect cellular respiration. Since cellular respiration is so vital to bodily functions, many of these diseases severely affect individuals.
The most common diseases affecting glycolysis are pyruvate kinase deficiency, erythrocyte hexokinase deficiency, and glucose phosphate isomerase deficiency.
These diseases are typically inherited in an autosomal recessive manner and individuals who are homozygous (i.e., have two affected genes), for these diseases develop hemolytic anemia, jaundice, and splenomegaly.
Deficiencies in the pyruvate dehydrogenase enzyme can interfere with pyruvate oxidation. These can result in lactic acidosis characterized by a build-up of lactate and increased serum alanine due to pyruvate build-up that then undergoes fermentation to lactic acid.
Children born with these deficiencies may have neurological defects, and management of the disease typically includes keto-diets or diets high in fats.
There are several enzymes in the TCA cycle that may be affected and result in disease, including succinyl-CoA synthase and fumarase. Many individuals with these disorders have involuntary muscle spasms and posture, called dystonia, and are deaf.
Mitochondrial myopathies are genetic disorders that may affect the production of enzymes involved in the electron transport chain or oxidative phosphorylation.
These diseases are classically characterized by muscle weakness and fatigue and may include muscular paralysis.
Additionally, exposure to high amounts of certain drugs or toxic chemicals can affect the electron transport chain or oxidative phosphorylation. Substances that can directly inhibit complexes in the electron transport chain include carbon monoxide and cyanide.
Other substances may inhibit ATP synthase, such as oligomycin, or disrupt the connection between the electron transport chain and ATP synthase (i.e., an electron transport chain uncoupler), such as aspirin or 2,4-dinitrophenol.