Krebs cycle
Tricarboxylic acid cycle (Krebs cycle, citrate cycle) is the central part of the general pathway of catabolism, a cyclic biochemical aerobic process during which two- and three-carbon compounds are converted, which are formed as intermediate products in living organisms during the breakdown of carbohydrates, fats and proteins, to CO 2. In this case, the released hydrogen is sent to the tissue respiration chain, where it is further oxidized to water, taking a direct part in the synthesis of a universal energy source - ATP.
The Krebs cycle is milestone respiration of all cells using oxygen, the center of intersection of many metabolic pathways in the body. In addition to a significant energy role, the cycle is also assigned a significant plastic function, that is, it is an important source of precursor molecules, from which, in the course of other biochemical transformations, such important compounds for cell life as amino acids, carbohydrates, fatty acids, etc. are synthesized.
The cycle of transformation citric acid in living cells was discovered and studied by the German biochemist Hans Krebs, for this work he (together with F. Lipman) was awarded the Nobel Prize (1953).
| substrates | Products | Enzyme | Reaction type | A comment | |
|---|---|---|---|---|---|
| 1 | Oxaloacetate + Acetyl-CoA+ H2O |
Citrate + CoA-SH |
citrate synthase | Aldol condensation | the limiting stage converts C 4 oxaloacetate to C 6 |
| 2 | Citrate | cis-aconiate + H2O |
aconitase | Dehydration | reversible isomerization |
| 3 | cis-aconiate + H2O |
isocitrate | hydration | ||
| 4 | Isocitrate + |
isocitrate dehydrogenase | Oxidation | NADH is formed (equivalent to 2.5 ATP) | |
| 5 | Oxalosuccinate | α-ketoglutarate + CO2 |
decarboxylation | reversible stage C 5 is formed |
|
| 6 | α-ketoglutarate + NAD++ CoA-SH |
succinyl-CoA+ NADH+H++ CO2 |
alphaketoglutarate dehydrogenase | Oxidative decarboxylation | NADH is formed (equivalent to 2.5 ATP), regeneration C 4 way (released by CoA) |
| 7 | succinyl-CoA+ GDP + P i |
succinate + CoA-SH+ GTP |
succinyl coenzyme A synthetase | substrate phosphorylation | or ADP ->ATP , 1 ATP is formed |
| 8 | succinate + ubiquinone (Q) |
fumarate + ubiquinol (QH 2) |
succinate dehydrogenase | Oxidation | FAD is used as a prosthetic group (FAD->FADH 2 in the first stage of the reaction) in the enzyme, equivalent to 1.5 ATP |
| 9 | fumarate + H2O |
L-malate | fumarase | H 2 O connection (hydration) |
|
| 10 | L-malate + NAD+ |
oxaloacetate + NADH+H+ |
malate dehydrogenase | oxidation | NADH is formed (equivalent to 2.5 ATP) |
The general equation for one revolution of the Krebs cycle is:
Acetyl-CoA → 2CO 2 + CoA + 8e −Wikimedia Foundation. 2010 .
KREBS CYCLE- (citric and tricarboxylic acid cycle), a system of biochemical reactions by which most EUKARYOTIC organisms obtain their main energy as a result of the oxidation of food. Occurs in mitochondrial cells. Includes several chemical ... ... Scientific and technical encyclopedic dictionary
Krebs cycle- The tricarboxylic acid cycle, a cycle of successive reactions in the cells of aerobic organisms, which result in the synthesis of ATP molecules Biotechnology topics EN Krebs cycle … Technical Translator's Handbook
krebs cycle- - a metabolic pathway leading to the complete destruction of acetyl CoA to the final products - CO2 and H2O ... Concise Dictionary of Biochemical Terms
Krebs cycle- trikarboksirūgščių ciklas statusas T sritis chemija apibrėžtis Baltymų, riebalų ir angliavandenių oksidacinio skaidymo organizme ciklas. atitikmenys: engl. citric acid cycle; Krebs cycle; tricarboxylic acid cycle Krebs cycle; lemon cycle ... ... Chemijos terminų aiskinamasis žodynas
Krebs cycle- tricarboxylic acid (Krebs, citric acid) cycle tricarboxylic acid cycle, Krebs cycle. The most important cyclic sequence of metabolic reactions in aerobic organisms (eu and prokaryotes), as a result of which a sequential ... ... Molecular biology and genetics. Dictionary.
KREBS CYCLE- the same as the tricarboxylic acid cycle ... Natural science. encyclopedic Dictionary
Krebs Cycle, Citric Acid Cycle- a complex cycle of reactions, where enzymes act as catalysts; these reactions take place in the cells of all animals and consist in the decomposition of acetate in the presence of oxygen with the release of energy in the form of ATP (along the electron transfer chain) and ... ... medical terms
KREBS CYCLE, CITRIC ACID CYCLE- (citric acid cycle) a complex cycle of reactions, where enzymes act as catalysts; these reactions take place in the cells of all animals and consist in the decomposition of acetate in the presence of oxygen with the release of energy in the form of ATP (along the transmission chain ... ... Explanatory Dictionary of Medicine
KREBS CYCLE (tricarboxylic acid cycle- citric acid cycle) is a complex cyclic enzymatic process in which pyruvic acid is oxidized in the body with the formation of carbon dioxide, water and energy in the form of ATP; takes central position in common system… … Glossary of botanical terms
Tricarboxylic acid cycle- Tsik ... Wikipedia
The Krebs cycle is a closed system of biochemical redox reactions. The cycle is named after the English biochemist Hans Krebs, who postulated and experimentally confirmed the main reactions of aerobic oxidation. For his research, Krebs received Nobel Prize(1953). The cycle has two more names:
the tricarboxylic acid cycle, since it includes the reactions of the transformation of tricarboxylic acids (acids containing three carboxyl groups);
The citric acid cycle, since the first reaction of the cycle is the formation of citric acid.
The Krebs cycle includes 10 reactions, four of which are redox. During the reactions, 70% of the energy is released.
Extremely large biological role this cycle, since it is the common end point of the oxidative breakdown of all major food products. This is the main mechanism of oxidation in the cell, figuratively it is called the metabolic "boiler". In the process of oxidation of fuel molecules (carbohydrates, amino acids, fatty acids), the body is provided with energy in the form of ATP. Fuel molecules enter the Krebs cycle after being converted into acetyl-Co-A.
In addition, the tricarboxylic acid cycle supplies intermediates for biosynthetic processes. This cycle takes place in the mitochondrial matrix. Consider the reactions of the Krebs cycle
The cycle begins with the condensation of the four-carbon component of oxaloacetate and the two-carbon component of acetyl-Co-A. The reaction is catalyzed by citrate synthase and is an aldol condensation followed by hydrolysis. The intermediate product is citryl-Co-A, which is hydrolyzed to citrate and CoA:
Reactions 4 and 5 are oxidative decarboxylation, catalyzed by isocitrate dehydrogenase, the reaction intermediate is oxalosuccinate.
Succinyl-CoA + ~ P + GDP Succinate + GTP + CoA
The phosphoryl group of GTP is easily transferred to ADP to form ATP:
GTP + ADP ATP + GDP
This is the only reaction of the cycle that is a reaction of substrate phosphorylation.
VIII. This is the third redox reaction:
X. Fourth redox reaction:
In the Krebs cycle, carbon dioxide, protons, electrons. Four reactions of the cycle are redox, catalyzed by enzymes - dehydrogenases containing the coenzymes NAD, FAD. Coenzymes capture the resulting H + and ē and transfer them to the respiratory chain (biological oxidation chain). The elements of the respiratory chain are located on the inner membrane of the mitochondria.
The acetyl-SCoA formed in the PVC-dehydrogenase reaction then enters into tricarboxylic acid cycle(CTC, citric acid cycle, Krebs cycle). In addition to pyruvate, keto acids coming from catabolism are involved in the cycle. amino acids or any other substances.
The cycle runs in mitochondrial matrix and represents oxidation molecules acetyl-SCoA in eight consecutive reactions.
In the first reaction, they bind acetyl and oxaloacetate(oxaloacetic acid) to form citrate(citric acid), then citric acid isomerizes to isocitrate and two dehydrogenation reactions with concomitant release of CO 2 and reduction of NAD.
In the fifth reaction, GTP is formed, this is the reaction substrate phosphorylation. Next, FAD-dependent dehydrogenation occurs sequentially succinate (succinic acid), hydration fumaric acid up malate(malic acid), then NAD-dependent dehydrogenation with the formation of oxaloacetate.
As a result, after eight reactions of the cycle again oxaloacetate is formed .
The last three reactions make up the so-called biochemical motif (FAD-dependent dehydrogenation, hydration and NAD-dependent dehydrogenation, it is used to introduce a keto group into the succinate structure. This motif is also present in fatty acid β-oxidation reactions. In reverse order (reduction, de hydration and recovery) this motif is observed in fatty acid synthesis reactions.
1. Energy
2. Anabolic. In the CTC are formed
Enzymes catalyzing the 1st, 3rd and 4th reactions of TCA are sensitive to allosteric regulation metabolites:
chief and basic the regulator of the TCA is oxaloacetate, or rather its availability. The presence of oxaloacetate involves acetyl-SCoA in the TCA cycle and starts the process.
Usually the cell has balance between the formation of acetyl-SCoA (from glucose, fatty acids or amino acids) and the amount of oxaloacetate. The source of oxaloacetate is pyruvate, (formed from glucose or alanine), derived from aspartic acid as a result of transamination or the AMP-IMF cycle, and also from fruit acids the cycle itself (succinic, α-ketoglutaric, malic, citric), which can be formed during the catabolism of amino acids or come from other processes.
Regulation of enzyme activity pyruvate carboxylase carried out with the participation acetyl-SCoA. It is allosteric activator enzyme, and without it, pyruvate carboxylase is practically inactive. When acetyl-SCoA accumulates, the enzyme starts to work and oxaloacetate is formed, but, of course, only in the presence of pyruvate.
Also most amino acids during their catabolism, they are able to turn into metabolites of TCA, which then go to oxaloacetate, which also maintains the activity of the cycle.
Cycle replenishment reactions with new metabolites (oxaloacetate, citrate, α-ketoglutarate, etc.) are called anaplerotic.
An example of a significant role oxaloacetate serves to activate the synthesis of ketone bodies and ketoacidosis blood plasma at insufficient the amount of oxaloacetate in the liver. This condition is observed during decompensation of insulin-dependent diabetes mellitus (type 1 diabetes) and during starvation. With these disorders, the process of gluconeogenesis is activated in the liver, i.e. the formation of glucose from oxaloacetate and other metabolites, which entails a decrease in the amount of oxaloacetate. Simultaneous activation of fatty acid oxidation and accumulation of acetyl-SCoA triggers a backup pathway for the utilization of the acetyl group - synthesis of ketone bodies. In this case, the body develops acidification of the blood ( ketoacidosis) with a characteristic clinical picture: weakness, headache, drowsiness, decreased muscle tone, body temperature and blood pressure.
The described method of regulation with the participation of oxaloacetate is an illustration of the beautiful formulation " Fats burn in the flame of carbohydrates". It implies that the "burning flame" of glucose leads to the appearance of pyruvate, and pyruvate is converted not only into acetyl-SCoA, but also into oxaloacetate. The presence of oxaloacetate guarantees the inclusion of an acetyl group formed from fatty acids in the form of acetyl-SCoA, in the first reaction of the TCA.
In the case of a large-scale "burning" of fatty acids, which is observed in the muscles during physical work and in the liver fasting, the rate of entry of acetyl-SCoA in the TCA reaction will directly depend on the amount of oxaloacetate (or oxidized glucose).
If the amount of oxaloacetate in hepatocyte not enough (no glucose or it is not oxidized to pyruvate), then the acetyl group will go to the synthesis of ketone bodies. This happens when prolonged fasting and type 1 diabetes.
Brief historical information
Our favorite cycle is the CTC, or the Cycle of tricarboxylic acids - life on Earth and under the Earth and in the Earth ... Stop, but in general this is the most amazing mechanism - it is universal, it is by oxidizing the decay products of carbohydrates, fats, proteins in the cells of living organisms, as a result we get energy for the activity of our body.
This process was discovered by Hans Krebs himself, for which he received the Nobel Prize!
He was born in August 25 - 1900 in the German city of Hildesheim. He received a medical education from the University of Hamburg, continued biochemical research under the guidance of Otto Warburg in Berlin.
In 1930, together with a student, he discovered the process of neutralizing ammonia in the body, which was in many representatives of the living world, including humans. This cycle is the urea cycle, also known as the Krebs cycle #1.
When Hitler came to power, Hans emigrated to the UK, where he continues to study science at Cambridge and Sheffield universities. Developing the research of the Hungarian biochemist Albert Szent-Györgyi, he gets an insight and makes the most famous Krebs cycle No. 2, or in other words the "Szent-Györgyi-Krebs cycle" - 1937.
The research results are sent to the journal "Nature", which refuses to publish the article. Then the text flies to the magazine "Enzymologia" in Holland. Krebs receives the 1953 Nobel Prize in Physiology or Medicine.
The discovery was amazing: in 1935, Szent-Györgyi found that succinic, oxaloacetic, fumaric and malic acids (all 4 acids are natural chemical components of animal cells) enhance the oxidation process in the pectoral muscle of a pigeon. Which has been shredded.
It is in it that metabolic processes proceed at the highest speed.
F. Knoop and K. Martius in 1937 found that citric acid is converted into isocitric acid through an intermediate product, cis - aconitic acid. In addition, isocitric acid could be converted into a-ketoglutaric acid, and that acid into succinic acid.
Krebs noticed the effect of acids on the absorption of O2 by the pectoral muscle of the pigeon and revealed their activating effect on the oxidation of PVC and the formation of Acetyl-Coenzyme A. In addition, the processes in the muscle were inhibited by malonic acid, which is similar to succinic acid and could competitively inhibit enzymes whose substrate is succinic acid .
When Krebs added malonic acid to the reaction medium, the accumulation of a-ketoglutaric, citric and succinic acids began. Thus, it is clear that the joint action of a-ketoglutaric, citric acids leads to the formation of succinic.
Hans investigated more than 20 substances, but they did not affect the oxidation. Comparing the data obtained, Krebs received a cycle. At the very beginning, the researcher could not say exactly whether the process begins with citric or isocitric acid, so he called it the "tricarboxylic acid cycle".
Now we know that the first is citric acid, so the correct one is the citrate cycle or the citric acid cycle.
In eukaryotes, TCA reactions take place in mitochondria, while all the enzymes for catalysis, except for 1, are contained in the free state in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is localized on the inner mitochondrial membrane and is incorporated into the lipid bilayer. In prokaryotes, the reactions of the cycle take place in the cytoplasm.
Let's meet the participants of the cycle:
1) Acetyl-Coenzyme A:2) PIE - Oxaloacetate - Oxalic-Acetic acid:
as it consists of two parts: oxalic and acetic acid.
3-4) Citric and Isocitric acids:
5) a-Ketoglutaric acid:
6) Succinyl-Coenzyme A:
7) Succinic acid:
8) Fumaric acid:
9) Malic acid:
How do reactions take place? In general, we are all used to the appearance of the ring, which is shown below in the picture. Everything is listed in stages below:
1. Condensation of Acetyl-Coenzyme A and Oxal-Acetic acid ➙ citric acid.
The transformation of Acetyl-Coenzyme A originates from the condensation with Oxalo-Acetic acid, resulting in the formation of citric acid.
The reaction does not require the consumption of ATP, since the energy for this process is provided as a result of the hydrolysis of the thioether bond with Acetyl-Coenzyme A, which is macroergic:
2. Citric acid passes through cis-aconitic acid into isocitric acid.
Citric acid is isomerized to isocitric acid. The conversion enzyme - aconitase - first dehydrates citric acid to form cis-aconitic acid, then combines water to the double bond of the metabolite, forming isocitric acid:
3. Isolicitric acid is dehydrogenated to form a-ketoglutaric acid and CO2.
Isolicitric acid is oxidized by a specific dehydrogenase, the coenzyme of which is NAD.
Simultaneously with the oxidation, isocitric acid is decarboxylated. As a result of transformations, α-ketoglutaric acid is formed.
4. Alpha-ketoglutaric acid is dehydrated ➙ succinyl-coenzyme A and CO2.
The next step is the oxidative decarboxylation of α-ketoglutaric acid.
It is catalyzed by the α-ketoglutarate dehydrogenase complex, which is similar in mechanism, structure and action to the pyruvate dehydrogenase complex. As a result, succinyl-CoA is formed.
5. Succinyl-coenzyme A ➙ succinic acid.
Succinyl-CoA is hydrolyzed to free succinic acid, the released energy is stored by the formation of guanosine triphosphate. This stage is the only one in the cycle where energy is directly released.
6. Succinic acid is dehydrated ➙ fumaric.
Dehydrogenation of succinic acid is accelerated by succinate dehydrogenase, its coenzyme is FAD.
7. Fumaric hydrated ➙ malic.
Fumaric acid, which is formed during the dehydrogenation of succinic acid, is hydrated and malic acid is formed.
8. Malic acid is dehydrogenated ➙ Oxalic-Acetic - the cycle is closed.
The final process is the dehydrogenation of malic acid catalyzed by malate dehydrogenase;
The result of the stage is a metabolite from which the cycle of tricarboxylic acids begins - Oxalic Acetic Acid.
In 1 reaction of the next cycle, another ml of Acetyl-Coenzyme A will enter.
How to remember this cycle? Just!
1) Very figurative expression:2) Another long poem:
Pike ate acetate, it turns out citrate,
Through cisaconite it will be isocitrate.
Having given up hydrogen OVER, it loses CO2,
Alpha-ketoglutarate is immensely happy about this.
Oxidation is coming - NAD has stolen hydrogen,
TDP, coenzyme A take CO2.
And the energy barely appeared in succinyl,
Immediately ATP was born and succinate remained.
So he got to FAD - he needs hydrogen,
Fumarate drank water, and turned into malate.
Then OVER came to malate, acquired hydrogen,
The PIKE reappeared and quietly hid.
3) The original poem is shorter:
PIKE ACETYL LIMONIL,
But Narcissus Horse was afraid
He is above him ISOLIMONO
ALPHA - KETOGLUTARAL.
SUCCINATED WITH COENZYME,
AMBER FUMAROVO,
APPLES in store for the winter,
Turned into a PIKE again.
Hello! Summer is coming, which means that all sophomores of medical universities will take biochemistry. A difficult subject, really. To help a little those who repeat the material for exams, I decided to make an article in which I will tell you about the "golden ring" of biochemistry - the Krebs cycle. It is also called the tricarboxylic acid cycle and the citric acid cycle, which are all synonyms.
I will write the reactions themselves in. Now I will talk about why the Krebs cycle is needed, where it goes and what are its features. I hope it will be clear and accessible.
First, let's understand what metabolism is. This is the basis without which the understanding of the Krebs Cycle is impossible.
One of the most important properties alive (remember) - this is a metabolism with environment. Indeed, only creature can absorb something from the environment, and then release something into it.
In biochemistry, metabolism is called "metabolism". Metabolism, the exchange of energy with the environment is metabolism.
When we, say, ate a chicken sandwich, we got proteins (chicken) and carbohydrates (bread). During digestion, proteins break down into amino acids and carbohydrates into monosaccharides. What I have described now is called catabolism, that is, the breakdown of complex substances into simpler ones. The first part of metabolism is catabolism.
One more example. The tissues in our body are constantly being renewed. When the old tissue dies, its fragments are pulled apart by macrophages, and they are replaced by new tissue. New tissue is created in the process of protein synthesis from amino acids. Protein synthesis occurs in ribosomes. The creation of a new protein (complex substance) from amino acids (simple substance) is anabolism.
So anabolism is the opposite of catabolism. Catabolism is the destruction of substances, anabolism is the creation of substances. By the way, so as not to confuse them, remember the association: “Anabolics. Blood and sweat". This is a Hollywood movie (rather boring in my opinion) about athletes using anabolics for muscle growth. Anabolics - growth, synthesis. Catabolism is the reverse process.
How are metabolism and the Krebs cycle related? The fact is that it is the Krebs cycle that is one of the key points where anabolism and catabolism converge. This is where its significance lies.
Let's break it down in diagrams. Catabolism can be roughly represented as the breakdown of proteins, fats and carbohydrates in our digestive system. So, we ate food from proteins, fats, and carbohydrates, what's next?
Further, in the cytoplasm of the cell, the transformation of these simple substances in pyruvic acid(she is pyruvate). From the cytoplasm, pyruvic acid enters the mitochondria, where it turns into acetyl coenzyme A. Please remember these two substances, pyruvate and acetyl CoA, they are very important.
Let's now see how the stage that we have just painted happens:
An important detail: amino acids can turn into acetyl CoA immediately, bypassing the stage of pyruvic acid. Fatty acid immediately converted to acetyl CoA. Let's take this into account and edit our schema to get it right:
The transformation of simple substances into pyruvate occurs in the cytoplasm of cells. After that, pyruvate enters the mitochondria, where it is successfully converted to acetyl CoA.
Why is pyruvate converted to acetyl CoA? Precisely in order to start our Krebs cycle. Thus, we can make one more inscription in the scheme, and we get the correct sequence:
As a result of the reactions of the Krebs cycle, substances important for life are formed, the main of which are:
Water and carbon dioxide are also released. Let's reflect this in our diagram:
By the way, the entire Krebs cycle takes place in the mitochondria. Exactly where it goes preparatory stage, that is, the conversion of pyruvate to acetyl CoA. Not for nothing, by the way, mitochondria are called the "energy station of the cell."
The Krebs cycle is amazing in that it not only provides us with valuable ATP (energy) and coenzymes for cellular respiration. If you look at the previous diagram, you will understand that the Krebs cycle is a continuation of the processes of catabolism. But at the same time, it is also the first step of anabolism. How is this possible? How can the same cycle both destroy and create?
It turns out that individual products of the reactions of the Krebs cycle can be partially sent for the synthesis of new complex substances, depending on the needs of the body. For example, gluconeogenesis is the synthesis of glucose from simple substances that are not carbohydrates.
Let's try to reflect this on the diagram so that the Krebs cycle is designated exactly as the point of intersection of decay and synthesis.
With blue arrows, I marked the paths of anabolism, that is, the creation of new substances. As you can see, the Krebs cycle is indeed the point of intersection of many processes of both destruction and creation.
