Krebs Cycle

Krebs Cycle

The Krebs cycle is part of the process used by cells to convert foodstuffs, such as carbohydrates, into usable energy. The cycle was named for Sir Hans Adolf Krebs who first explained its operation in 1936. It is also referred to as the citric acid cycle or the tricarboxylic acid (TCA) cycle. The Krebs cycle has a key role in the metabolism of humans and animals. Metabolism is the sum of all biochemical processes involved in life and is divided into two subcategories: anabolism and catabolism. Anabolism is the building up of large organic molecules from simpler precursors, and catabolism is the breakdown of complex substances into simpler molecules. The Krebs cycle is primarily a catabolic process because it breaks down larger carboxylic acids into smaller units. This process involves oxidative reactions which release chemical free energy; some of this energy is lost as heat and the rest of it is conserved by coupling it with molecules capable storing energy.

Since the early 1900s, many biochemists, including Harden, Meyerhof, and Warburg, have contributed to the understanding of cellular metabolism. In 1928, Szent-Györgyi found that four different four-carbon acids could stimulate oxygen uptake in tissue samples. He theorized that these carboxylic acids must play a role in changing carbohydrates into energy. In 1937, the German-born British biochemist Hans Adolf Krebs (1900-1981) found that six-carbon acids, particularly citric acid, were also involved in this process. He eventually detailed the entire cycle through which foods are changed into energy.

The Krebs cycle consists of a series of six chemical reactions which occur in a repeating loop. These reactions take place inside cellular organelles known as mitochondria, which can be thought of as tiny energy "factories." These factories release hydrogen by breaking bonds between carbon atoms in the food molecules. After each step, the fuel molecule is shortened and it goes on to the next step in the process. The hydrogen released in this process is eventually transferred to another molecule known as adenosine triphosphate (ATP).

ATP is an organic compound composed of adenine, the sugar ribose, and three phosphate groups. When ATP is broken down by subsequent hydrolysis, it yields adenosine diphosphate (ADP), inorganic phosphorus, and energy. The released energy is used to fuel almost all cellular functions. The Krebs cycle is only one portion of carbohydrate catabolism. It occurs between the other stages which are glycolysis and oxidative phosphorylation.

The first step of the Krebs cycle acts upon a material known as acetyl coenzyme A (acetyl CoA), which is a derivative of the vitamin called pantothenic acid. Acetyl CoA is formed from fatty acids or glucose prior to entering the cycle. Fuel molecules, such as carbohydrates, fats, and proteins, must be converted to acetyl CoA before they can be utilized in the the Krebs cycle. Acetyl CoA enters at the start of the cycle and reacts with oxaloacetic acid to form citric acid. The energy that is released in this reaction is stored in the form of ATP. Citric acid, a six carbon acid, then begins the next step in the cycle. It is broken down to form ketoglutaric acid, a 5 carbon acid. The third step breaks down ketoglutaric acid to yield succinic acid, which contains 4 carbons. The fourth step begins with succinic acid and converts it to oxaloacetic acid. Oxaloaetic acid then starts the cycle all over again by reacting with more acetyl CoA.

Each of the steps in the Krebs cycle is catalyzed by a specific enzyme. As carbons are removed from the carboxylic acids they are converted to carbon dioxide, which animals expire as a metabolic byproduct. The hydrogens which are removed are bound to a vitamin-derived carrier compound, nicotinamide adenine dinucleotide (NAD), which eventually stores the energy in the form of ATP.

In most higher plants, in certain microorganisms, such as the bacterium Escherichia coli, this process operates slightly differently and is called the glyoxylate cycle, because its primary intermediate is glyoxylic acid.