Citric Acid Cycle (Krebs Cycle)

Chapter: Anatomy and Physiology for Health Professionals: Levels of Organization : Cellular Metabolism

The citric acid cycle is also called the tricarboxylic acid cycle or the TCA cycle.

Citric Acid Cycle (Krebs Cycle)

The citric acid cycle is also called the tricarboxylic acid cycle or the TCA cycle. It is a sequence of enzymatic reactions involving the metabolism of carbon chains of glucose, fatty acids, and amino acids to yield car-bon dioxide, water, and high-energy phosphate bonds (ATP). The three-carbon pyruvic acids enter the mito-chondria, each losing a carbon. They then combine with a coenzyme to form a two-carbon acetyl CoA and release more high-energy electrons; then, each acetyl CoA combines with a four-carbon oxaloacetic acid to form a six-carbon citric acid. During the eight steps of this cycle, citric acid atoms are rearranged to produce various intermediate molecules, most of which are keto acids. Eventually, the acetic acid will be totally disposed and the pickup molecule (oxaloacetic acid) will be regenerated. The citric acid (Krebs) cycle produces two carbon dioxide molecules and four mol-ecules of reduced coenzymes.

A series of reactions removes two carbons, synthesizes one ATP, and releases more high-energy electrons (FIGURE 4-5). When food is ingested, large macromolecules are broken down to simple mole-cules. Proteins are broken down into amino acids, carbohydrates are broken down into simple sugars (glucose), and fats are broken down into both glyc-erol and fatty acids. In fact, all food carbohydrates are eventually transformed into glucose. The breakdown of simple molecules to acetyl CoA is accompanied by the production of limited amounts of ATP (via glycolysis) and high-energy electrons.

Glucose, through glycolysis, is converted into pyruvic acid. Glycerol and amino acids are also broken down into pyruvic acid. Actually, all these processes result in differing ways in acetyl CoA. Complete oxidation of acetyl CoA to H₂O and CO₂ produces high-energy electrons, which yield greater amounts of ATP via the electron transport chain.

In the TCA cycle, the process of oxidation provides more molecules of ATP.

The following summarizes the citric acid (Krebs) cycle:

■■ Decarboxylation: A pyruvic acid carbon is removed and released as carbon dioxide gas. This diffuses into the blood for expulsion by the lungs. This is the first time carbon dioxide is released during cellular respiration.

■■ Oxidation: Acetic acid, the remaining 2C frag-ment, is oxidized via removal of hydrogen atoms. These atoms are picked up by NAD⁺.

■■ Acetyl CoA formation: The final reactive product, acetyl CoA, is produced when acetic acid com-bines with coenzyme A. This coenzyme contains sulfur that is derived from vitamin B5.

Electron Transport Chain

In the electron transport chain, the high-energy elec-trons still contain most of the chemical energy of the original glucose molecule. Special carrier molecules bring them to enzymes that store most of the remain-ing energy in more ATP molecules; heat and water are also produced. Oxygen is the final electron acceptor in this step; hence, the overall process being termed aerobic respiration (FIGURE 4-6).

For cellular respiration, glucose and oxygen are required. This process produces carbon diox-ide, water, and energy. Nearly half of the energy is recaptured as high-energy electrons stored in the cells through the synthesis of ATP. This process is an example of oxidative phosphorylation. Most of the involved components of the electron transport chain are proteins bound to cofactors (metal atoms). They form multiprotein complexes embedded in the inner mitochondrial membrane. Some of these proteins are flavins (from riboflavin), whereas others contain iron and sulfur. However, most of these proteins are cyto-chromes (iron-containing pigments). Four respiratory enzyme complexes are formed by the nearby clustered carriers. These complexes are reduced and oxidized as they pick up electrons and move them on to the next complex in the chain.

The electron transport chain converts energy via release of electronic energy to pump protons (from the matrix) to the intermembrane space. An electrochem-ical proton (H⁺) gradient is created across the inner mitochondrial membrane. This gradient has potential energy and can perform tasks. The only parts of the membrane freely permeable to H⁺ are ATP synthases, which are large complexes consisting of enzymes and proteins. An electrical current is created and ATP synthase uses it to catalyze attachment of a phosphate group to ADP, forming ATP.

Each ATP molecule has a chain of three chemical groups, called phosphates. Some of the energy is recap-tured in the bond of the end phosphate. When energy is needed later, the terminal phosphate bond breaks to release the stored energy. Cells use ATP for many functions, including active transport and the synthesis of needed compounds.

When an ATP molecule has lost its terminal phosphate, it becomes an ADP molecule. ADP can be converted back into ATP by adding energy and a third phosphate. ATP and ADP molecules shuttle between the energy -releasing reactions of cellular respiration and the energy-using reactions of the cells (FIGURE 4-7).