III.

How Cellular Respiration Works

The process of cellular respiration occurs in four stages: glycolysis; the transition stage; the Krebs cycle, also known as the citric acid cycle; and the electron transport chain. Each stage accomplishes different tasks.

A.

Glycolysis

Glucose is the primary fuel used in glycolysis, the first stage of cellular respiration. This all-important molecule is found in the cell’s cytoplasm, the gel-like substance that fills the cell. Glucose consists of 6 carbon, 12 hydrogen, and 6 oxygen atoms bonded together, along with electrons (negatively charged atomic particles) associated with each atom. Of these components, only the hydrogen atoms and certain electrons participate directly in glycolysis.

In glycolysis, glucose is broken down with the help of enzymes and other molecules found in the cytoplasm. Enzymes first attach two phosphate groups to glucose to make it more reactive. A phosphate group is a cluster of one phosphorus and four oxygen atoms. The addition of the two phosphate groups prepares glucose for the action of another enzyme. This enzyme splits glucose in half to produce two three-carbon molecules, each with one phosphate group attached.

In the next step, an enzyme removes one hydrogen atom and two electrons from each three-carbon molecule. Both hydrogen atoms are modified to hydrogen ions, positively charged particles. A hydrogen ion and two electrons from each three-carbon molecule are transferred as a unit to a large molecule called nicotinamide adenine dinucleotide (NAD⁺⁾ to form two molecules of NADH. The hydrogen ions and electrons stored in each molecule of NADH are used to make ATP in later stages of cellular respiration.

In the final steps of glycolysis, two hydrogen atoms are removed from each three-carbon compound. These hydrogen atoms bond to free-floating oxygen atoms in the cytoplasm to form water. This step prepares the two three-carbon compounds for action by the next enzyme in the pathway. This enzyme removes the phosphate group from each three-carbon compound. Each phosphate group then bonds to a single molecule of adenosine diphosphate (ADP). ADP is composed of three carbon-based rings and a tail of two phosphate groups. The addition of the third phosphate group to the tail forms ATP. In this step, two new ATP molecules are produced. When cells require energy, another enzyme breaks off the third phosphate group, releasing energy that powers the cell. The removal of the third phosphate from ATP converts ATP back to ADP, which is used again in cellular respiration to make more ATP.

When the two three-carbon compounds are separated from the phosphate groups, the three-carbon compounds are converted to two molecules of pyruvate, each composed of three carbon, three oxygen, and three hydrogen atoms. When glycolysis is complete, important products used in the next steps of cellular respiration have been produced: two molecules of NADH and two molecules of pyruvate. The two ATP molecules gained in glycolysis are used for reactions in the cell that require energy.

B.

Transition Stage

The pyruvate molecules move from the cytoplasm to special structures in the cell called mitochondria, where the remaining steps of cellular respiration are carried out. Each mitochondrion contains a membrane that is folded back and forth many times. This extensive membrane is studded with hundreds of thousands of enzymes that direct cellular respiration. The numerous enzymes enable great quantities of ATP to be produced simultaneously in one mitochondrion. Without mitochondria or a similar structure, most cells could not generate enough ATP to survive.

The transition stage is a short biochemical pathway that links glycolysis with the Krebs cycle. In this brief stage, enzymes transfer hydrogens and electrons from the two pyruvate molecules to two molecules of NAD⁺ to form two more molecules of NADH. Another enzyme breaks off one carbon and two oxygen atoms from each pyruvate molecule. These atoms combine to form carbon dioxide, the primary waste product of cellular respiration, which diffuses out of the cell. As a result of these reactions, each pyruvate molecule is transformed into a two-carbon compound called an acetyl group. The two acetyl groups unite with two molecules of coenzyme A to form two acetyl coenzyme A molecules. The acetyl coenzyme A molecules are the molecules that enter the Krebs cycle.

C.

Krebs Cycle

During the Krebs cycle, the acetyl coenzyme A molecules are processed. As this complex pathway progresses, six molecules of NADH are formed. Additional carbon dioxide is created, and this process releases energy that is used to build two molecules of ATP from a pool of ADP and phosphate groups in the mitochondria. Hydrogens and electrons then are transferred to a molecule of flavin adenine dinucleotide (FAD⁺⁺)to form FADH₂, a molecule like NADH that temporarily stores hydrogen and electrons for later use. By the end of the Krebs cycle, most of the usable energy from the original glucose molecule has been transferred to ten molecules of NADH (two from glycolysis, two from the transition stage, and six from the Krebs cycle); two molecules of FADH₂; and four molecules of ATP, two of which were formed in glycolysis.

D.

Electron Transport Chain

The reactions of the electron transport chain occur in several closely spaced molecules embedded in the mitochondrial membrane. Acting like specialized delivery trucks, the NADH and FADH₂ molecules dump off their load of electrons and hydrogen ions near these electron transport chain molecules. The first molecule in the chain has an attraction for electrons and grabs them, but the molecule next to it in the chain has an even stronger attraction and grabs the electrons away from the first molecule. The electrons are passed down the chain in this manner, until they reach oxygen, the final molecule in the chain. Oxygen has a stronger appetite for electrons than any molecule in the chain, and the electrons therefore are held by oxygen. They are joined by the hydrogen ions that were dropped off by NADH and FADH₂ at the beginning of the electron transport chain. The combination of the electrons, hydrogen ions, and oxygen forms water, used by the cell in other biochemical reactions. As NADH and FADH₂ release hydrogen and electrons in the electron transport chain, they are converted back to NAD⁺ and FAD⁺⁺, respectively, providing the cell with a steady supply of these molecules so that cellular respiration can be carried out over and over again.

As the electrons flow down the electron transport chain, they release a veritable windfall of energy that is used by an enzyme to make more ATP, again from the pool of ADP and phosphate groups in the mitochondria. In most cells, the electron transport chain produces 32 molecules of ATP. Together with the two ATP molecules gained in glycolysis and the four generated in the Krebs cycle, cellular respiration produces a grand total of 38 molecules of ATP for every molecule of glucose processed.

Glucose molecules enter the cell by the hundreds of thousands. They are processed simultaneously to generate millions of ATP molecules every second. Some of the ATP molecules remain in the mitochondria to supply it with needed energy, but the majority stream from the mitochondria to the cytoplasm, where they fuel the cell’s activities. It is estimated that a single human brain cell uses a staggering 10 million ATP molecules per second to carry out its tasks.

Although glucose is the primary fuel for cellular respiration, cells can rely on other molecules to produce ATP. The cellular respiration pathway is connected to other metabolic pathways that can donate molecules to cellular respiration at different steps along the way. For example, glycerol, a breakdown product of fat, can enter the cellular respiration pathway in the middle of glycolysis. Another product of fat digestion, fatty acids, can enter at the transition stage. Glycerol is modified in glycolysis to pyruvate, and fatty acids are modified to acetyl coenzyme A in the transition stage. The pyruvate and acetyl coenzyme A are processed through the remaining steps of cellular respiration to yield ATP. The ability to use alternate molecules enables cells to keep ATP production going even if they run out of glucose. Marathon runners, for example, first use up their glucose reserves to make ATP, and then draw on their fat reserves to generate the ATP needed to get to the finish line.