Under aerobic conditions, Pyruvate produced by glycolysis is the process of finally producing oxaloacetic acid through a series of reactions. Because the key compound in the cycle is citric acid, it is called citric acid cycle, and because citric acid has three carboxyl groups, it is called tricarboxylic acid cycle. In order to commemorate the contribution made by German scientist Hans Krebs in clarifying the citric acid cycle, this cycle is also called [Krebs cycle]. The citric acid cycle is carried out in the mitochondria of cells. Pyruvate undergoes decarboxylation and dehydrogenation through the citric acid cycle. Carboxyl groups form carbon dioxide, and hydrogen atoms enter the electron transfer chain with the carrier for oxidative phosphorylation to form water molecules and release energy to synthesize ATP. Citric acid cycle is the same way that various fuel molecules such as pyruvate, fatty acids and amino acids undergo oxidative decomposition. < P > Acetyl -CoA enters the circulation system composed of a series of reactions. It is oxidized to produce H2O and CO2. Since this cyclic reaction starts with the condensation of acetyl -CoA with oxaloaceticacid to produce citric acid containing three carboxyl groups, it is called tricarboxylic acid cycle or citric acid cycle. In the tricarboxylic acid cycle, the reaction catalyzed by citric acid synthase is the key step, and the supply of oxaloacetic acid is conducive to the smooth progress of the cycle. The detailed process is as follows:
1. Acetyl-CoA enters the tricarboxylic acid cycle?
Acetyl -CoA has thioester bond, and acetyl group has enough energy to perform aldol condensation with carboxyl group of oxaloacetic acid. Firstly, histidine residue of citrate synthase acts as a base with acetyl -CoA, so that the methyl group of acetyl -CoA loses an h+, and the generated carbon anion carries out nucleophilic attack on carbonyl carbon of oxaloacetic acid to generate citroyl-CoA intermediate, and then the high-energy thioester bond is hydrolyzed to release free citric acid. Make the reaction proceed irreversibly to the right. The reaction is catalyzed by citratesynthase, which is a strong energy release reaction. The synthesis of citric acid from oxaloacetic acid and acetyl -CoA is an important adjustment point of tricarboxylic acid cycle. Citrate Synthase is an allosteric enzyme, ATP is an allosteric inhibitor of citrate synthase. In addition, α-ketoglutarate and NADH can allosterically inhibit its activity, and long-chain fatty acyl-.
2. Isocitric acid formation?
The tertiary alcohol group of citric acid is not easy to be oxidized, but it is easy to be oxidized when it is converted into isocitric acid and the tertiary alcohol is converted into secondary alcohol. This reaction is a reversible reaction catalyzed by cis-aconitase.
3. First oxidation deacidification?
under the action of isocitrate dehydrogenase, the secondary alcohol of isocitrate is oxidized to carbonyl, and the intermediate product of oxalosuccinicacid is generated, which is rapidly decarboxylated on the same enzyme surface to generate α-ketoglutarate (α? Ketoglutarate), NADH and co2. This reaction is β-oxidative decarboxylation, which requires Mg2+ as activator. This reaction is irreversible and is the rate-limiting step in the tricarboxylic acid cycle. ADP is the activator of isocitrate dehydrogenase, while ATP ATP,NADH are the inhibitors of this enzyme. < P >?
4. Second oxidative decarboxylation?
under the action of α-ketoglutarate dehydrogenase system, α-ketoglutarate undergoes oxidative decarboxylation to produce succinyl -CoA, NADH H+and co2. The reaction process is completely similar to that catalyzed by pyruvate dehydrogenase system, belonging to α? Oxidative decarboxylation, a part of the energy generated by oxidation is stored in the high-energy thioester bond of succinyl-coa. The α-ketoglutarate dehydrogenase system is also composed of three enzymes (α-ketoglutarate decarboxylase, lipoic acid succinyl transferase, dihydrolipoic acid dehydrogenase) and five coenzymes (tpp, lipoic acid, HS-CoA, NAD+, FAD). This reaction is also irreversible. α -ketoglutarate dehydrogenase complex is inhibited by ATP, GTP, NADH and succinyl -CoA, but it is not regulated by phosphorylation/dephosphorylation. < P >?
5. the substrate is phosphorylated to produce ATP?
Under the action of succinatethiokinase, the thioester bond of succinyl -CoA is hydrolyzed, and the released free energy is used to synthesize gtp. In bacteria and higher organisms, ATP can be directly generated. In mammals, GTP is generated and then ATP is generated. At this time, succinyl -CoA generates succinic acid and coenzyme A.
6. dehydrogenation of succinic acid?
succinatedehydrogenase catalyzes the oxidation of succinic acid to fumaric acid. This enzyme is bound to the inner membrane of mitochondria, while other enzymes circulating tricarboxylic acid exist in the matrix of mitochondria. This enzyme contains iron-sulfur center and fad with valence of * *. Electrons from succinic acid pass through the fad and iron-sulfur center, and then enter the electron transfer chain to O2. Malonic acid is an analogue of succinic acid, which is a powerful competitive inhibitor of succinate dehydrogenase, so.
Tricarboxylic acid cycle 7. Hydration of fumaric acid?
fumarase only acts on trans double bonds of fumaric acid, but has no catalytic effect on maleic acid, so it is highly stereospecific.
8. oxaloacetic acid regeneration?
under the action of malicdehydrogenase, the secondary alcohol group of malic acid is dehydrogenated and oxidized to carbonyl group, and oxaloacetate is generated. NAD+is the coenzyme of dehydrogenase, and it accepts hydrogen to become NADH H+(Figure 4-5).
in this cycle, oxaloacetic acid is initially consumed by participating in the reaction, but it is regenerated after the cycle. Therefore, the net result is that one acetyl group is consumed through two decarboxylations in each cycle. The carbon dioxide generated by decarboxylation of organic acids in the cycle is the main source of carbon dioxide in the body. In the tricarboxylic acid cycle, * * * has four dehydrogenation reactions, and the released hydrogen atoms enter the respiratory system in the form of NADH+H+ and FADH2. Finally, it is transferred to oxygen to generate water, and the energy released in this process can be synthesized into ATP. Acetyl coenzyme A is not only produced by the decomposition of sugar, but also by the catabolism of fatty acids and amino acids, which all enter the tricarboxylic acid cycle for complete oxidation. Any substance that can be converted into any intermediate metabolite in the tricarboxylic acid cycle can be oxidized through the tricarboxylic acid cycle. Therefore, the tricarboxylic acid cycle is actually the same pathway for the terminal oxidation of organic substances such as sugar, fat and protein in organisms. The tricarboxylic acid cycle is not only a catabolic pathway, but also provides precursor molecules for the biosynthesis of some substances. For example, oxaloacetic acid is the precursor for the synthesis of aspartic acid. α-ketoglutaric acid is a precursor for the synthesis of glutamic acid. Some amino acids can also be converted into sugars by this route.
Summary of the Tricarboxylic acid cycle
Acetyl-CoA+3NAD+Fad+GDP+PI-→ 2CO2+3NADH+FadH2+GTP+2H+CoA-SH
. Oxidative decarboxylation, the coenzyme is nad+, they first dehydrogenate the substrate to produce oxaloacetic acid, and then decarboxylate it with the cooperation of Mn2+ or Mg2+ to produce α-ketoglutarate. α-ketoglutarate dehydrogenase system catalyzes α? The oxidative decarboxylation reaction is basically the same as that promoted by pyruvate dehydrogenase system mentioned above. It should be pointed out that the generation of Co2 by decarboxylation is a universal law of Co2 generation in the body, so it can be seen that the process of Co2 generation in the body is completely different from that of Co2 generation by external combustion.
2. The four dehydrogenations of tricarboxylic acid cycle, in which three pairs of hydrogen atoms take NAD+ as the acceptor and one pair takes FAD as the acceptor, are respectively reduced to generate NADH+H+ and FADH2. They are transferred through the intramitochondrial hydrogen transfer system, and finally combine with oxygen to generate water. In this process, the released energy makes adp and pi combine to generate ATP. Where NADH+H+ participates in the hydrogen transfer system, Three molecules of ATP are generated, while the hydrogen transfer system in which FADH2 participates generates two molecules of ATP. In addition, one molecule of citric acid participates in the tricarboxylic acid cycle until the end of the cycle * * * generates 12 molecules of ATP.
3. Acetyl -CoA enters the cycle and condenses with oxaloacetic acid, a four-carbon acceptor molecule, to generate six-carbon citric acid. In the tricarboxylic acid cycle, it undergoes secondary decarboxylation to generate two molecules of Co2, which is equal to the number of carbon atoms of dicarbonyl acetyl entering the cycle. However, the carbon lost by Co2 is not from two carbon atoms of acetyl, but from oxaloacetic acid.
4. In the middle of tricarboxylic acid cycle. Theoretically, it can be recycled without consumption, but because some components in the cycle can also participate in the synthesis of other substances, and other substances can also generate intermediate products through various channels, it is said that the components of the tricarboxylic acid cycle are constantly being updated.
For example, oxaloacetic acid-→ aspartic acid
α-ketoglutaric acid-→ glutamic acid
oxaloacetic acid-→ pyruvic acid-→ alanine
Among them, the reaction of oxaloacetic acid catalyzed by pyruvate carboxylase is the most important. Because the content of oxaloacetic acid directly affects the circulation speed, continuous supplementation of oxaloacetic acid makes the tricarboxylic acid cycle smooth.