The Krebs cycle takes place in y cells. Krebs cycle, biological role, basic reactions. Enzymes of the Krebs cycle. Intersection point of decay and synthesis

Krebs cycle? What it is?

If you are not aware, then this is the tricarboxylic acid cycle. Do you understand?

If not, then this is a key step in the respiration of all cells that use oxygen. By the way, Hans Krebs received the Nobel Prize for the discovery of this cycle.

In general, as you understand, this thing is very important, especially for biochemists. They are interested in the question How to quickly memorize the Krebs cycle?»

Here's what it looks like:

In essence, the Krebs cycle describes the steps in the conversion of citric acid. They need to be remembered.

1. Condensation of acetyl-coenzyme A with oxaloacetic acid leads to the formation of citric acid.
2. Citric acid is converted to isocitric acid through cisaconite.
3. Isocitric acid is dehydrogenated to form alpha-ketoglutaric acid and carbon dioxide.
4. Alpha-ketoglutaric acid is dehydrated to form succinyl-coenzyme A and carbon dioxide.
5. Succinyl coenzyme A is converted to succinic acid.
6. Succinic acid is dehydrated to form fumaric acid.
7. Fumaric acid hydrates to form malic acid.
8. Malic acid is dehydrated to form oxaloacetic acid. In this case, the cycle is closed. A new molecule of acetyl coenzyme A enters the first reaction of the next cycle.

Actually, I didn't understand everything. I'm more interested in how to remember it.

How to remember the Krebs cycle? Verse!

There is a wonderful verse that allows you to remember this cycle. The author of this verse is a former student of KSMU, she composed it back in 1996.

PIKE at ACETIL LEMON silt,
But nar CIS with BUT KOH I was afraid
He's over him ISOLIMONN about
ALPHA-KETOGLUTAR alas.

SUCCINIL Xia COENZYME om,
AMBER silt FUMAROV about,
YABLOCH ek stocked up for the winter,
turned around PIKE oh again.

Here, the substrates of the reactions of the tricarboxylic acid cycle are sequentially encrypted:

• ACETYL-coenzyme A
• Lemon acid
• cisaconitic acid
• isocitric acid
• ALPHA-KETOGLUTARIC ACID
• SUCCINIL-COENZYME A
• Succinic acid
• Fumaric acid
• Apple acid
• PIKE (oxaloacetic acid)

Another verse to remember the tricarboxylic acid cycle:

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.

The verse is good. Of course, you still need to remember it, then the question: “How to remember the Krebs cycle” will not excite students.

How to remember the Krebs cycle? Story!

In addition, I propose the following thing - to transform each of these stages (acid) into images and pictures:

PIKE- oxaloacetic acid
AC tech fights with ETI- acetyl-coenzyme A
LEMON- lemon acid
CIS turn with KOH yami - cisaconite
Drawn on canvas ( ISO) LEMON- isocitric acid
ALF keeps GLU lateral TAP y - alpha-ketoglutaric acid
on the SUK u sits and saws it CINI j - succinyl-coenzyme A
AMBER- succinic acid
in UGH razhke IDA la - fumaric acid
APPLE- Apple acid

Alf Aztec
Amber Yeti

Now you need to connect them in series with each other. And then the Krebs Cycle will be remembered as follows.

Near the wide river, the PIKE began to jump out of the water and attack the Azteca and the ETI, who fought each other from the bottom. Having showered them with LEMONS, the Aztec and the children sat on a tank with horses and quickly began to get out of this place. They did not notice how they crashed into the gate, which was depicted (ISO) LEMON. From the inside, the gate was opened to them by ALF, holding a glass DEEP TARA. At this time, the CYNIC sitting on the Bitch began to throw AMBER stones at them. Hiding behind caps with MARLE, our heroes hid behind huge APPLES. But it turns out that the PIKE turned out to be cunning and were waiting for them for apples.

Phew, finally finished writing this story. The fact is that coming up with such a story in your head is very fast. Literally 1-2 minutes. But to state it in text, and even so that others understand it is completely different.

Memorizing the Krebs cycle with an acronym

A Whole Pineapple And A Slice Of Soufflé Today Is Actually My Lunch, which corresponds to citrate, cis-aconitate, isocitrate, (alpha-)ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaloacetate.

I hope now you understand how you can remember the Krebs Cycle.

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 are involved in the cycle, coming from the catabolism of amino acids or any other substances.

Tricarboxylic acid cycle

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 to form 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.

DTC functions

1. Energy

• generation hydrogen atoms for the operation of the respiratory chain, namely three NADH molecules and one FADH2 molecule,
• single molecule synthesis GTP(equivalent to ATP).

2. Anabolic. In the CTC are formed

• heme precursor succinyl-SCoA,
• keto acids that can be converted into amino acids - α-ketoglutarate for glutamic acid, oxaloacetate for aspartic,
• lemon acid, used for the synthesis of fatty acids,
• oxaloacetate, used for glucose synthesis.

Anabolic reactions of the TCA

Regulation of the tricarboxylic acid cycle

Allosteric regulation

Enzymes catalyzing the 1st, 3rd and 4th reactions of TCA are sensitive to allosteric regulation metabolites:

Regulation of oxaloacetate availability

chief and main 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

1)pyruvic acid formed from glucose or alanine,

Synthesis of oxaloacetate from pyruvate

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.

2) Getting from aspartic acid as a result of transamination or from the AMP-IMF cycle,

3) Receipt from fruit acids the cycle itself (amber, α-ketoglutaric, malic, citric) formed during the catabolism of amino acids or in other processes. Majority 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.

Replenishment of the pool of TCA metabolites from amino acids

Cycle replenishment reactions with new metabolites (oxaloacetate, citrate, α-ketoglutarate, etc.) are called anaplerotic.

The role of oxaloacetate in metabolism

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.

Change in the rate of TCA reactions and the reasons for the accumulation of ketone bodies under certain conditions

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.

Metabolism

Metabolism is the energy exchange that takes place in our body. We inhale oxygen and exhale carbon dioxide. Only a living being can take something from the environment and return it back in a different form.

Let's say we decided to have breakfast and ate chicken bread. Bread is carbohydrates, chicken is proteins.
During this time, digested carbohydrates will break down into monosaccharides, and proteins into amino acids.
This is the initial stage - catabolism. At this stage, according to their structure, complex ones break down into simpler ones.

Also, as an example, the renewal of the surface of the skin. They are constantly changing. When the top layer of the skin dies, macrophages remove dead cells and new tissue appears. It is created by collecting protein from organic compounds. It takes place in the ribosomes. The set of actions of the emergence of a complex composition (protein) from a simple one (amino acids) is called anabolism.

Anabolism:

• growth,
• increase,
• extension.

Catabolism:

• splitting,
• division,
• reduction.

The name can be remembered by watching the movie "Anabolics". There we are talking about athletes who use anabolic drugs to grow and increase muscle mass.

What is the Krebs Cycle?

In the 30s of the 20th century, the scientist Hans Krebs was studying urea. Then he moves to England and comes to the conclusion that certain enzymes are catalyzed in our body. For this he was awarded the Nobel Prize.

We get energy from the glucose contained in red blood cells. The action of converting dextrose into energy is assisted by mitochondria. The end product is then converted to adenosine triphosphate or ATP. It is ATP that is the main value of the body. The resulting substance saturates the organs of our body with energy. Glucose itself cannot be converted into ATP; this requires complex mechanisms. This transition is called the Krebs cycle.

Krebs cycle are constant chemical transformations occurring inside every living being. So it is called, as the procedure is repeated without stopping. As a result of this phenomenon, we acquire adenosine triphosphoric acid, which is considered vital for us.

An important condition is the respiration of the cell. During the passage of all stages, oxygen must be present. At this stage, the creation of new amino acids and carbohydrates also occurs. These elements play the role of builders of the body, one can say that this phenomenon performs another significant role - building. For the effectiveness of these functions, other micro and macro elements and vitamins are also needed. With a lack of at least one element, the work of the organs is disrupted.

Stages of the Krebs cycle

Here, one molecule of glucose is divided into two parts of pyruvic acid. It is an important link in the metabolic process and the work of the liver depends on it. It is found in many fruits and berries. It is often used for cosmetic purposes. As a result, lactic acid may also appear. It is found in the cells of the blood, brain, muscles. Then we get coenzyme A. Its function is to carry carbon to different parts of the body. When added with oxalate, we get citrate. Coenzyme A completely decomposes, we also get a water molecule.

In the second, water is separated from citrate. As a result, an acatin compound appears, it will help in obtaining isocitrate. So, for example, we can find out the quality of fruits and juices, nectars. NADH is formed - it is necessary for oxidative processes and metabolism.
There is a process of connection with water, and the energy of adenosine triphosphate is released. Obtaining oxalocetate. Functions in mitochondria.

What causes energy metabolism to slow down?

Our body has the ability to adapt to food, fluids and how much we move. These things greatly affect metabolism.
Even in those distant times, humanity survived in difficult weather conditions with diseases, hunger, and crop failures. Now medicine has moved forward, so in developed countries people began to live longer and earn better money without putting all their strength. Nowadays, people are more likely to consume flour, sweet confectionery and move little. This way of life leads to a slowdown in the work of the elements.

To avoid this, first of all, it is necessary to include citrus fruits in the diet. They contain a complex of vitamins and other important substances. An important role is played by citric acid contained in its composition. It plays a role in the chemical interaction of all enzymes and is named after the Krebs cycle.

Taking citrus fruits will help solve the problem of energy interaction, also if you follow a healthy lifestyle. You can not often eat oranges, tangerines, as they can irritate the walls of the stomach. A little bit of everything.

Tricarboxylic acid cycle (Krebs cycle)

Tricarboxylic acid cycle was first discovered by the English biochemist G. Krebs. He was the first to postulate the significance of this cycle for the complete combustion of pyruvate, the main source of which is the glycolytic conversion carbohydrates. Later it was shown that the cycle of tricarboxylic acids is the center where almost all metabolic pathways converge. Thus, Krebs cycle- common end path oxidation acetyl groups (in the form of acetyl-CoA), into which it is converted in the process catabolism most of the organic molecules, playing the role of "cellular fuel»: carbohydrates, fatty acids and amino acids.

Formed as a result of oxidative decarboxylation pyruvate in mitochondria acetyl-CoA enters Krebs cycle. This cycle takes place in the matrix mitochondria and consists of eight successive reactions(Fig. 10.9). The cycle begins with the addition of acetyl-CoA to oxaloacetate and the formation citric acid (citrate). Then lemon acid(six-carbon compound) by a series dehydrogenation(taking away hydrogen) and two decarboxylations(cleavage of CO 2) loses two carbon atom and again in Krebs cycle turns into oxaloacetate (four-carbon compound), i.e. as a result of a full turn of the cycle one molecule acetyl-CoA burns to CO 2 and H 2 O, and molecule oxaloacetate is regenerated. Consider all eight successive reactions(stages) Krebs cycle.

Rice. 10.9.Tricarboxylic acid cycle (Krebs cycle).

First reaction catalyzed enzyme cit-rat-synthase, while acetyl the acetyl-CoA group condenses with oxaloacetate, resulting in the formation of lemon acid:

Apparently, in this reactions associated with enzyme citril-CoA. Then the latter spontaneously and irreversibly hydrolyzes to form citrate and HS-KoA.

As a result of the second reactions formed lemon acid undergoes dehydration with the formation of cis-aconitic acids, which, by adding molecule water, goes into isocitric acid(isocitrate). Catalyzes these reversible reactions hydration-dehydration enzyme aconitate hydratase (aconitase). As a result, there is a mutual movement of H and OH in molecule citrate:

Third reaction seems to limit the speed Krebs cycle. isocitric acid dehydrogenated in the presence of NAD-dependent iso-citrate dehydrogenase.

During isocitrate dehydrogenase reactions isocitric acid simultaneously decarboxylated. NAD-dependent isocitrate dehydrogenase is allosteric enzyme, which as a specific activator needed ADP. Besides, enzyme to express your activity needs to ions Mg 2+ or Mn 2+ .

During the fourth reactions oxidative decarboxylation of α-ketoglutaric acids with the formation of a high-energy compound succinyl-CoA. The mechanism of this reactions similar to that reactions oxidative decarboxylation pyruvate to acetyl-CoA, the α-ketoglutarate dehydrogenase complex resembles the pyruvate dehydrogenase complex in its structure. In both one and the other case, reactions take part 5 coenzymes: TPP, amide lipoic acid, HS-KoA, FAD and NAD+.

Fifth reaction catalyzed enzyme succinyl-CoA-synthetase. During this reactions succinyl-CoA with the participation of GTP and inorganic phosphate turns into succinic acid (succinate). At the same time, the formation of a high-energy phosphate bond of GTP occurs due to the high-energy thioether bond of succinyl-CoA:

As a result, the sixth reactions succinate dehydrated into fumaric acid. Oxidation succinate catalyzed succinate dehydrogenase, in molecule which since protein firmly (covalently) bound coenzyme FAD. In its turn succinate dehydrogenase strongly associated with the internal mitochondrial membrane:

seventh reaction carried out under the influence enzyme fumarate hydratase ( fumarases). Formed at the same time fumaric acid hydrated, product reactions is an Apple acid(malate). It should be noted that fumarate hydratase has stereospecificity(see chapter 4) – during reactions L-apple is formed acid:

Finally, during the eighth reactions tricarboxylic acid cycle under the influence of mitochondrial NAD-dependent malate dehydrogenase going on oxidation L-malate to oxaloacetate:

As can be seen, in one turn of the cycle, consisting of eight enzymatic reactions, complete oxidation("combustion") of one molecules acetyl-CoA. For continuous operation of the cycle, a constant supply of acetyl-CoA to the system is necessary, and coenzymes(NAD + and FAD), which have passed into the reduced state, must be oxidized again and again. This is oxidation carried out in the carrier system electrons in respiratory chain(in respiratory chain enzymes) localized in membrane mitochondria. The resulting FADH 2 is strongly associated with SDH, so it transmits atoms hydrogen via KoQ. released as a result oxidation acetyl-CoA energy is largely concentrated in macroergic phosphate bonds ATP. From 4 steam atoms hydrogen 3 couples transfer NADH to the transport system electrons; while counting on each couple in the system of biological oxidation formed 3 molecules ATP(during conjugated ), and in total, therefore, 9 molecules ATP(see chapter 9). One pair atoms from succinate dehydrogenase-FADH 2 enters the transport system electrons through KoQ, resulting in only 2 molecules ATP. During Krebs cycle one is also synthesized molecule GTP (substrate phosphorylation), which is equivalent to one molecule ATP. So, at oxidation one molecules acetyl-CoA in Krebs cycle and system oxidative phosphorylation may form 12 molecules ATP.

If we calculate the total energy effect of glycolytic cleavage glucose and subsequent oxidation two emerging molecules pyruvate to CO 2 and H 2 O, then it will be much larger.

As noted, one molecule NADH (3 molecules ATP) is formed during oxidative decarboxylation pyruvate to acetyl-CoA. When splitting one molecules glucose formed 2 molecules pyruvate, and oxidation up to 2 molecules acetyl-CoA and subsequent 2 turns tricarboxylic acid cycle synthesized 30 molecules ATP(hence, oxidation molecules pyruvate to CO 2 and H 2 O gives 15 molecules ATP). To this number must be added 2 molecules ATP formed during aerobic glycolysis, and 6 molecules ATP, synthesized by oxidation 2 molecules extramitochondrial NADH, which are formed during oxidation 2 molecules glyceraldehyde-3-phosphate in dehydrogenase reactions glycolysis. Therefore, when splitting into tissues one molecules glucose according to the equation C 6 H 12 O 6 + 6O 2 -> 6CO 2 + 6H 2 O, 38 is synthesized molecules ATP. Undoubtedly, in terms of energy, the complete splitting glucose is a more efficient process than anaerobic glycolysis.

It should be noted that the 2 molecules NADH in the future with oxidation can give not 6 molecules ATP, but only 4. The fact is that they themselves molecules extramitochondrial NADH are not able to penetrate through membrane inside mitochondria. However, they give electrons can be included in the mitochondrial chain of biological oxidation using the so-called glycerol phosphate shuttle mechanism (Fig. 10.10). Cytoplasmic NADH first reacts with cytoplasmic dihydroxyacetone phosphate to form glycerol-3-phosphate. Reaction catalysis

Rice. 10.10. Glycerol phosphate shuttle mechanism. Explanation in the text.

is controlled by NAD-dependent cytoplasmic glycerol-3-phosphate dehydrogenase:

Dihydroxyacetone phosphate + NADH + H +<=>Glycerol-3-phosphate + NAD +.

The resulting glycerol-3-phosphate easily penetrates through the mitochondrial membrane. Inside mitochondria another (mitochondrial) glycerol-3-phosphate dehydrogenase (flavin enzyme) oxidizes glycerol-3-phosphate again to dihydroxyacetone phosphate:

Glycerol-3-phosphate + FAD<=>Dihydroxyacetone phosphate + FADH 2.

restored flavoprotein(enzyme-FADH 2) introduces at the level of KoQ acquired by him electrons into the chain of biological oxidation and associated with it oxidative phosphorylation, and dihydroxyacetone phosphate comes out of mitochondria in cytoplasm and can again interact with cytoplasmic NADH + H + . Thus, pair electrons(from one molecules cytoplasmic NADH + H +), introduced into respiratory chain using a glycerol phosphate shuttle mechanism, gives not 3, but 2 ATP.

Rice. 10.11. Malate-aspartate shuttle system for the transfer of reducing equivalents from cytosolic NADH to the mitochondrial matrix. Explanation in the text.

Subsequently, it was shown that this shuttle mechanism is used only in skeletal muscles and the brain to transfer reduced equivalents from cytosolic NADH + H + to mitochondria.

AT cells liver, kidneys and heart, a more complex malate-as-partate shuttle system operates. The operation of such a shuttle mechanism becomes possible due to the presence malate dehydrogenase and aspartate aminotransferases both in the cytosol and in mitochondria.

It was found that from cytosolic NADH + H + reduced equivalents, first with the participation enzyme malate dehydrogenase(Fig. 10.11) are transferred to cytosolic oxaloacetate. As a result, malate is formed, which, with the help of a system that transports dicarboxylic acids, passes through the inner membrane mitochondria into the matrix. Here, malate is oxidized to oxaloacetate, and matrix NAD + is reduced to NADH + H + , which can now transfer its electrons in respiratory chain enzymes, localized on the inner membrane mitochondria. In turn, the resulting oxaloacetate in the presence of glutamate and enzyme ASAT enters into reaction transamination. The resulting aspartate and α-ketoglutarate, with the help of special transport systems, are able to pass through membrane mitochondria.

Transport in the cytosol regenerates the oxaloacetate, which triggers the next cycle. In general, the process includes easily reversible reactions, occurs without energy consumption, its "driving force" is a constant recovery NAD + in the cytosol by glyceraldehyde-3-phosphate, which is formed during catabolism glucose.

So, if the malate-aspartate mechanism functions, then as a result of the complete oxidation one molecules glucose may form not 36, but 38 molecules ATP(Table 10.1).

In table. 10.1 are given reactions, in which the formation of high-energy phosphate bonds occurs during catabolism glucose, indicating the efficiency of the process under aerobic and anaerobic conditions

Ministry of Education of the Russian Federation

Samara State Technical University

Department of Organic Chemistry

Abstract on the topic:

"THE CYCLE OF TRICABOXIC ACIDS (KREBS CYCLE)"

Completed by student: III - NTF - 11

Eroshkina N.V.

Checked.

The tricarboxylic acid cycle is also known as the Krebs cycle, since the existence of such a cycle was proposed by Hans Krebs in 1937.
For this, 16 years later, he was awarded the Nobel Prize in Physiology or Medicine. So, the discovery is very significant. What is the meaning of this cycle and why is it so important?

Whatever one may say, you still have to start quite afar. If you undertook to read this article, then at least by hearsay you know that the main source of energy for cells is glucose. It is constantly present in the blood in an almost unchanged concentration - for this there are special mechanisms that store or release glucose.

Inside each cell are mitochondria - separate organelles ("organs" of the cell) that process glucose to obtain an intracellular energy source - ATP. ATP (adenosine triphosphoric acid) is versatile and very convenient to use as an energy source: it is directly integrated into proteins, providing them with energy. The simplest example is the protein myosin, thanks to which muscles are able to contract.

Glucose cannot be converted into ATP, despite the fact that it contains a large amount of energy. How to extract this energy and direct it in the right direction without resorting to barbaric (by cellular standards) means such as burning? It is necessary to use workarounds, since enzymes (protein catalysts) allow some reactions to proceed much faster and more efficiently.

The first step is the conversion of a glucose molecule into two molecules of pyruvate (pyruvic acid) or lactate (lactic acid). In this case, a small part (about 5%) of the energy stored in the glucose molecule is released. Lactate is produced by anaerobic oxidation - that is, in the absence of oxygen. There is also a way to convert glucose under anaerobic conditions into two molecules of ethanol and carbon dioxide. This is called fermentation, and we will not consider this method.


...Just as we will not consider in detail the mechanism of glycolysis itself, that is, the breakdown of glucose into pyruvate. Because, to quote Leinger, "The conversion of glucose to pyruvate is catalyzed by ten enzymes acting in sequence." Those who wish can open a textbook on biochemistry and get acquainted in detail with all the stages of the process - it has been studied very well.

It would seem that the path from pyruvate to carbon dioxide should be quite simple. But it turned out that it is carried out through a nine-stage process, which is called the tricarboxylic acid cycle. This apparent contradiction with the principle of economy (couldn't it be simpler?) is partly due to the fact that the cycle connects several metabolic pathways: the substances formed in the cycle are precursors of other molecules that are no longer related to respiration (for example, amino acids), and any other compounds to be disposed of end up in the cycle and are either "burned" for energy or recycled into those that are in short supply.

The first step traditionally considered in relation to the Krebs cycle is the oxidative decarboxylation of pyruvate to an acetyl residue (Acetyl-CoA). CoA, if anyone does not know, is coenzyme A, which has a thiol group in its composition, on which it can carry an acetyl residue.


The breakdown of fats also leads to acetyls, which also enter the Krebs cycle. (They are synthesized similarly - from Acetyl-CoA, which explains the fact that only acids with an even number of carbon atoms are almost always present in fats).

Acetyl-CoA condenses with oxaloacetate to give citrate. This releases coenzyme A and a water molecule. This stage is irreversible.

Citrate is dehydrogenated to cis-aconitate, the second tricarboxylic acid in the cycle.

Cis-aconitate attaches back a water molecule, turning already into isocitric acid. This and the previous stages are reversible. (Enzymes catalyze both forward and reverse reactions - you know, right?)

Isocitric acid is decarboxylated (irreversibly) and simultaneously oxidized to give ketoglutaric acid. At the same time, NAD +, recovering, turns into NADH.

The next step is oxidative decarboxylation. But in this case, not succinate is formed, but succinyl-CoA, which is hydrolyzed at the next stage, directing the released energy to ATP synthesis.

This produces another NADH molecule and a FADH2 molecule (a coenzyme other than NAD, which, however, can also be oxidized and reduced, storing and releasing energy).

It turns out that oxaloacetate works as a catalyst - it does not accumulate and is not consumed in the process. So it is - the concentration of oxaloacetate in the mitochondria is maintained quite low. But how to avoid the accumulation of other products, how to coordinate all eight stages of the cycle?

For this, as it turned out, there are special mechanisms - a kind of negative feedback. As soon as the concentration of a certain product rises above the norm, this blocks the work of the enzyme responsible for its synthesis. And for reversible reactions, it is even simpler: when the concentration of the product is exceeded, the reaction simply starts to go in the opposite direction.

And a couple of minor remarks