Cellular Respiration

Cellular Respiration is an exergonic reaction through which organisms convert the chemical energy stored in sugars into a form that is directly useable by cells, ATP. It occurs (mostly) inside the mitochondria in cells and can be broken up into four parts: glycolysis, oxidation of pyruvate, the Krebs cycle, and oxidative phosphorylation.

Glycolysis

If you break apart the word glycolysis, you get "sugar" from glyco- and "splitting" from -lysis. Glycolysis is a metabolic process in which glucose is split into two three-carbon molecules known as pyruvate. There are ten enzyme-mediated reactions that occur as part of glycolysis, which we will not go into detail in here. The ten steps can be split into the "preparatory phase," which required two ATP, and the "payoff phase," which produces two NADH, four ATP, and two water molecules.

Glycolysis occurs in the cytoplasm of almost every cell, both prokaryotic and eukaryotic, which makes it a strong piece of evidence for common ancestry.

If you aren't familiar with the parts of the mitochondrion, click here.

Three of the four steps of cellular respiration take place inside mitochondria. As such, the descriptions of the following three steps will use the parts of the mitochondrion in an attempt to orient you as to what is happening and where. Here are the key parts that will be talked about, along with a visual image showing them.

Outer membrane: the outermost membrane of the mitochondrion

Inner membrane: the innermost membrane of the mitochondrion

Intermembrane Space: the region between the inner and outer mitochondrial membranes

Cristae: the folds on the inner membrane, which serve to increase surface area

Matrix: the space within the inner membrane

Oxidation of Pyruvate

In the second step of cellular respiration, the pyruvate previously made is oxidized. The pyruvate moves into the mitochondrial matrix through the use of pores and transport proteins known as pyruvate transporters.

Inside the matrix. there is something known as the pyruvate dehydrogenase complex, which uses three enzymes and five coenzymes. In this process, oxidative decarboxylation occurs, which removes the carboxyl group from pyruvate and releases it as a molecule of carbon dioxide. The remaining two carbons from the pyruvate become an acetyl group, which will be bound to Coenzyme A, to create acetyl-CoA. This oxidation, which centers around the transfer of electrons, produces a molecule of NADH.

This reaction will occur twice for each glucose molecule that we started with, as each glucose molecule produces two pyruvates.

The Krebs Cycle

The acetyl-CoA that was created in the last step will be used in a cycle of reactions known as the Krebs cycle, or the citric acid cycle, which also occurs in the mitochondrial matrix. There are eight enzyme-mediated steps to this metabolic process, four of which are oxidations. Through these oxidations, three molecules of NADH and one molecule of FADH2 are produced.

With each turn of this cycle, two carbons are added via the acetyl-CoA. In turn, two molecules of carbon dioxide are released with each cycle. In addition, one molecule of ATP, or GTP, is produced as a product of the cycle.

Isozymes are enzymes that have different structures, but complete the same function. Succinyl-CoA synthetase is an enzyme with isozymes that mediates the step of the cycle in which ATP or GTP is produced, depending on which isozyme is functioning as the catalyst. GTP, or guanosine triphosphate, is an analog to ATP that has guanine rather than adenine, but still functions as cellular energy.

What's the difference between NADH and FADH2?

NADH and FADH2 are both coenzymes that will bring electrons to an electron transport chain for the purpose of producing ATP.

NADH has more energetic electrons, so each NADH molecule will produce approximately 2.5 ATP, while each FADH2 will only produce 1.5 ATP molecules.

NADH

FADH2

Oxidative Phosphorylation

Oxidative Phosphorylation is the final step of cellular respiration, and it consists of two parts: the Electron Transport Chain and Chemiosmosis. Both of these occur on the inner mitochondrial membrane.

In the mitochondria, the electron transport chain (ETC) consists of a large number of molecules through which redox reactions will occur. Most are proteins that are easily oxidized, including four protein complexes and a protein known as cytochrome c, while one is a lipid-soluble coenzyme known as ubiquinone or coenzyme Q.

NADH will donate its electrons at Complex I, while FADH2 will donate electrons at Complex II. These electrons will move from one molecule to another in the ETC, until the final electron acceptor, molecular oxygen, is reached. The oxygen will be reduced and water will be produced.

Chemiosmosis uses the movement of H+ ions along an electrochemical gradient to power cellular work.

As electrons move down the ETC, they release energy. This energy is used to pump H+ ions across the membrane and from the mitochondrial matrix into the intermembrane space. This produces a gradient.

H+ ions will move across the now-present gradient via facilitated diffusion. As they move through ATP synthase, the enzyme catalyzes the phosphorylation of ADP into ATP. This produces the most ATP out of any step in the process, producing about 24-28 ATP per glucose molecule.

What if there's no oxygen present?

As you've learned, oxygen is the final electron acceptor for oxidative phosphorylation, making it required for the process. If there is no oxygen present, cellular respiration cannot fully occur. However, not only does oxidative phosphorylation fail to occur, but oxidation of pyruvate and the Krebs cycle will as well.


Glycolysis is an anaerobic process and will occur without any issue. However, there is a limit to how often it can occur on its own. Glycolysis uses NAD+ to make ATP and NADH. If the NADH is not being turned back into NAD+ via oxidative phosphorylation, eventually glycolysis will not be able to occur anymore and the ATP will stop being made.

This is where fermentation comes in. Fermentation uses NADH to convert pyruvate into byproducts, such as lactate or ethanol. The byproduct depends on the species - for example, we produce lactate via lactic acid fermentation, while yeast will produce ethanol and carbon dioxide. The reason your muscles burn after working out is from using up all their available oxygen and using fermentation to continue producing energy instead. The carbon dioxide produced by yeast is why bread rises or why beer is bubbly.