What Is the Citric Acid Cycle?

The tricarboxylic acid cycle (TCA cycle) is a common metabolic pathway in aerobic organisms. Prokaryotes are distributed in the cytoplasm, and eukaryotes are distributed in the mitochondria. Because the main intermediate metabolites in this cycle are organic acids containing three carboxyl groups, such as citric acid (C6), it is called the tricarboxylic acid cycle, also known as the citric acid cycle or TCA cycle. Or named Krebs Cycle after the name of the discoverer Hans Adolf Krebs (winning the Nobel Prize in Physiology or Medicine in 1953). The tricarboxylic acid cycle is the final metabolic pathway of the three major nutrients (sugars, lipids, and amino acids), and it is also the hub of the metabolic linkage of sugars, lipids, and amino acids.

The tricarboxylic acid cycle is a cyclic reaction system composed of a series of enzymatic reactions. In this reaction process, acetyl coenzyme A (C2) and oxaloacetate (OAA) (C4) are firstly formed to contain 3 carboxyl citric acid (C6), after 4 dehydrogenation (3 molecules of NADH + H + and 1 molecule of FADH2), 1 level of substrate phosphorylation, finally 2 molecules of CO ₂ are generated, and the cycle of oxaloacetate is regenerated reaction process.

The process of carbohydrates such as glucose or glycogen being oxidized thoroughly under aerobic conditions, producing carbon dioxide and water, and releasing energy is called aerobic oxidation of sugar. It has been found that in the presence of aerobic muscle, there is no lactic acid formation and no pyruvate accumulation, but energy is still released. Why? H. Well-known biochemist Kreb et al. Made a lot of research work to clarify the metabolism of pyruvate under aerobic conditions, and proposed the aerobic oxidation pathway of sugar, which won the Nobel Prize in 1953 for this purpose.

There is a common pathway between the aerobic oxidation of sugar and the anaerobic fermentation of sugar, namely glucose-pyruvate, the difference is the reaction after the formation of pyruvate. Under aerobic conditions, pyruvate is oxidatively decarboxylated to form acetyl CoA under the catalysis of a pyruvate dehydrogenase system, which is then oxidized to CO ₂ and H ₂ O by a tricarboxylic acid cycle.

Under aerobic conditions, lactic acid, the product of muscle glycogenolysis, may also be converted to pyruvate. For example, blood lactic acid can be used by tissues such as the heart muscle as an energy source, which is a response of the human body during the recovery period after intense exercise. During this recovery time, breathing still accelerates and deepens, and lactic acid reoxidizes to pyruvate, which is further oxidized to water and CO _{2 ^[1]}

Dr. Krebs had to flee to Britain during the persecution of the Nazis during the outbreak of World War II. Although he was a very good doctor in Germany, in the UK, because he did not have a medical license and was not recognized by society, he could only switch to basic medical research.

When he first chose the topic, just because he was interested in how food turns into water and carbon dioxide in the body, he chose this topic without hesitation, and set out to investigate the predecessors' research on this topic. Kind of material. In the report, he saw that some scholars reported: "Substance A became oxidized to substance B." Another scholar said: "Substance C became oxidized to substance D, and then further changed to substance E." Other scholars believe that: "Substance C is obtained from Substance B. Or it can be said that Substance F has become Substance G." Other scholars believe that it is "Substance G that has been oxidized to Substance A" and so on. Looking at research reports from all directions, Krebs thought that if these scattered data were sorted out, maybe the structure of food metabolism could be found. Just like playing a puzzle game, Krebs carefully sorted out these data, and found that food changes in the body in the order of F, G, A, B, C, D, and E. A closer look at the chemicals from A to F revealed that the chain was broken between E and F. If there is a substance X between E and F, then the food cycle reaction chain is complete. Concentrate immediately and search for substance X. Four years later, it was finally discovered that substance X is citric acid now used as a sour additive in beverages. He completed the food chain and named it

Acetyl-CoA appears in the cycle: Citric acid (I) is the first product in the cycle.

Acetyl-CoA + 3NAD ++ FAD + ADP + Pi + CoA-SH 2CO2 + 3NADH + FADH2 + ATP + 3H ++ CoA-SH

1. The formation of CO, there are two decarboxylation reactions in the cycle (reaction 3 and reaction 4)

Sugar aerobic oxidation is divided into two stages, the first stage

1. Provide energy for the body: When each mole of glucose is completely oxidized to H ₂ O and CO ₂ , the net production is 30 mol or 32 mol (the sugar principle generates 31 to 33 mol) of ATP. Therefore, under normal physiological conditions, various tissue cells (except red blood cells) obtain energy from the aerobic oxidation of sugar. The aerobic oxidation of sugar not only has high productivity, but also gradually releases energy and stores it in the ATP molecule, so the energy utilization rate is also very high.

2. The tricarboxylic acid cycle is a common oxidation pathway of three major nutrients: acetyl CoA, not only the product of sugar oxidation and decomposition, but also the product of fatty acid and amino acid metabolism, so the tricarboxylic acid cycle is actually the oxidation of large organic substances in the body Common main approach to energy supply. It is estimated that two thirds of the organic matter in the human body is decomposed by the j carboxylic acid cycle.

3. The tricarboxylic acid cycle is the hub of the three major metabolic links: -ketoglutarate, pyruvate, and oxaloacetate produced during the aerobic oxidation of sugars can be converted into corresponding amino acids by combining with ammonia; and these amino acids Deamination can be converted into the corresponding keto acid and enter the aerobic oxidation pathway of sugar. At the same time, glycerol produced by lipid catabolism and acetyl CoA produced by fatty acid metabolism can also enter the aerobic oxidation pathway of sugar for metabolism ^[2]

The biological significance of TCA can be divided into two aspects, 1. energy metabolism 2. material metabolism

1. The tricarboxylic acid cycle is the most effective way for the body to oxidize sugar or other substances to obtain energy. In sugar metabolism, sugar produces the most energy by oxidation through this pathway. Molecular glucose can produce 32 molecules of ATP or 30 molecules of ATP when aerobic oxidation produces H2O and CO2.

2. The tricarboxylic acid cycle is the hub of sugar, lipid, protein, and even nucleic acid metabolism, communication and transformation.

(1) Intermediate products of this cycle (such as oxaloacetate, -ketoglutarate) are raw materials for the synthesis of sugars, amino acids, fats, etc. Among them, OAA can be decarboxylated into PEP, participate in gluconeogenesis, and resynthesize energy in the body. acetylCOA can synthesize malonyl ACP and participate in palmitic acid synthesis. OAA can transaminate with the participation of transaminase, generate Asp, participate in urea cycl, and synthesize urea precursors such as arginine succinic acid. Some of these metabolites can also participate in the synthesis of purines and pyrimidines, and even synthesize porphyrin ring and participate in hemoglobin synthesis.

(2) TCA is a common pathway for the complete oxidative decomposition of sugars, proteins, and fats: protein hydrolysates (such as glutamic acid, aspartic acid, alanine, etc. after deamination or transamination) Only through the tricarboxylic acid cycle can it be completely oxidized and generate a large amount of energy; the fatty acid after decomposition of the fatty acid undergoes -oxidation to form acetyl CoA and glycerol. Glycerol also generates acetyl CoA through the EMP pathway. Thoroughly oxidized. All pathways of glucose metabolism eventually generate Pyruvate, which is dehydrogenated to acetyl-CoA and participates in TCA.

In summary, the tricarboxylic acid cycle is linked to the metabolism of three major substances and is also the hub of energy metabolism.