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🧬 Біохімія з нуля: Гексозомонофосфатний (пентозофосфатний) шунт — Transcript

by Алла Іщенко_Біохімія для лікаря і не тільки 😉 · 3,901 words · 764 segments · language en · Watch on YouTube

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0:00Welcome to our channel for the study of
0:02medical biochemistry.
0:04Today, we are discussing the pentose
0:06phosphate pathway, or as it is often
0:08called, the hexose monophosphate shunt.
0:13We will talk about this process, its
0:15localization, main stages and key
0:17enzymes, the biological significance of
0:19its products, NADPH and ribose 5-
0:21phosphate, and the link between the
0:23hexose monophosphate pathway and
0:25glycolysis, as well as its operation
0:27based on cellular needs.
0:31And of course, we will discuss
0:33pathologies related to this pathway, the
0:35deficiency of the enzyme glucose-6-
0:37phosphate dehydrogenase, and the
0:39consequences for the human body.
0:43So, let's begin.
0:44When characterizing glucose metabolism
0:46in a cell, we have already examined this
0:49scheme several times.
0:51We start almost every lecture on
0:52carbohydrate metabolism with it.
0:56Today, we will talk about a special
0:58pathway, because we have already covered
1:00glucose oxidation under various
1:02conditions, glycolysis reactions, and
1:04the synthesis and breakdown of glycogen
1:06.
1:07Today, we will talk about an alternative
1:10pathway where ribose 5-phosphate and
1:12reduced NADPH are produced.
1:14This is the pentose phosphate pathway or
1:17hexose monophosphate pathway.
1:19It is also called a shunt or a pathway.
1:21We will clarify how they differ as we go
1:23through the lecture.
1:25So, let's start.
1:27If you like our material, please give us
1:29a like and leave a comment for feedback
1:31.
1:34So, the hexose monophosphate pathway is
1:36an alternative metabolic pathway for
1:38glucose, or more precisely glucose-6-
1:41phosphate, in the cytosol of cells,
1:43which ensures the formation of reduced
1:45NADPH and pentose phosphates.
1:48What are its main characteristics?
1:50It is localized in the cytosol of the
1:52cell.
1:53The starting substrate is glucose-6-
1:55phosphate.
1:56This pathway is not a direct source of
1:59ATP energy.
2:00Its biological role is completely
2:02different. It consists of two stages.
2:05We will talk about them later.
2:08It also has a very close interconnection
2:10with glycolysis through shared
2:12metabolites and can, accordingly, switch
2:14between them.
2:17And the intensity of this pathway
2:18depends on the cell's needs for reduced
2:21NADPH and ribose 5-phosphate.
2:23Let's look at the general
2:25characteristics of the hexose
2:26monophosphate pathway.
2:28And if we look at the general equation,
2:30it will look like this.
2:33Six molecules of glucose-6-phosphate are
2:35converted into five molecules of glucose
2:37-6-phosphate through interaction,
2:39resulting in the formation of six
2:41molecules of CO2.
2:43The most important thing is that 12
2:45molecules of reduced NADPH are produced
2:48. This general equation can be written
2:50as a multiple of two—sorry, divided by
2:52two.
2:53Yes, here we can write three molecules
2:56of glucose-6-phosphate and six molecules
2:58of reduced NADP.
3:00This will then produce two molecules of
3:02glucose-6-phosphate and CO2.
3:08Now, to characterize these two stages,
3:10the hexose monophosphate pathway itself
3:12consists of the first oxidative stage,
3:14characterized by the sequential
3:16oxidation of glucose-6-phosphate.
3:20And as a result of this sequential
3:22oxidation, we see that two molecules of
3:25reduced NADPH are generated per one
3:27molecule of glucose-6-phosphate.
3:30And as a result of this stage, one
3:32molecule of carbon dioxide is released
3:34from each molecule of glucose-6-
3:35phosphate.
3:38As a result of this stage, we obtain a
3:40molecule of ribulose 5-phosphate.
3:44These reactions are irreversible.
3:47And the second stage is called the
3:49non-oxidative stage or non-oxidizing.
3:51Here, the interconversion of pentose
3:53phosphates takes place.
3:56These reactions are reversible and can
3:58proceed in the opposite direction.
4:02Regarding the significance of this stage
4:04, it occurs when the cell does not need
4:06ribose-5-phosphate.
4:10And then, as a consequence, it can be
4:12produced to the end.
4:14It is precisely because of this
4:16non-oxidative stage that we encounter
4:18glycolytic intermediates here.
4:21Therefore, due to this stage, the
4:23pentose phosphate pathway is linked to
4:25glycolysis.
4:28And here, at this stage, the main
4:30enzymes are transketolase and
4:32transaldolase.
4:36That is, the transfer of certain
4:38fragments occurs here.
4:41Let's examine these stages in more
4:43detail.
4:45Oxidative stage.
4:47So, the first reaction of the oxidative
4:49stage is the conversion of glucose-6-
4:51phosphate to 6-phosphogluconolactone.
4:55Changes occur right here at the first
4:57carbon atom.
4:59And so, into the first stage, we enter
5:01six molecules of glucose-6-phosphate.
5:04The enzyme that oxidizes, meaning it
5:06removes electrons and protons here, is
5:09glucose-6-phosphate dehydrogenase.
5:13The coenzyme is an NADP molecule, which
5:15takes on these protons and electrons.
5:19And it is regenerated into a reduced
5:21form, into six molecules of reduced NADP
5:24.
5:26Furthermore, one must remember that the
5:28enzyme glucose-6-phosphate dehydrogenase
5:31is a regulatory enzyme.
5:35It determines the speed of this pathway
5:37, and the activity of this enzyme
5:39depends on the ratio of oxidized NADP to
5:42reduced NADP.
5:47Thus, if there is a lot of oxidized NADP
5:49, it promotes enzyme activity, and
5:51conversely, a high concentration of
5:54reduced NADP inhibits the enzyme.
5:57Also, the activity of glucose-6-
5:59phosphate dehydrogenase can change under
6:01the influence of the hormone insulin.
6:04After all, insulin promotes the
6:06utilization of glucose through various
6:08pathways, including lipid synthesis.
6:11And it is precisely for lipid synthesis
6:13that we need reduced NADP. Therefore, in
6:16lipogenic tissues, this pathway is also
6:18activated under the influence of insulin
6:20. So, as a result of this first reaction
6:23of the oxidative stage, we obtained 6-
6:25phosphogluconolactone.
6:27Next, the second reaction occurs.
6:326-phosphogluconolactone, with the help
6:35of the enzyme lactonase or 6-
6:36phosphogluconolactonase, undergoes
6:38conversion and oxidation at this
6:40position to form 6-phosphogluconic acid
6:42.
6:47That is, we add a water molecule, and as
6:49a result, we get the opening of such a
6:51cycle.
6:54Next, the third reaction.
6:566-phosphogluconic acid with the help of
6:59the enzyme 6-phosphogluconate
7:01dehydrogenase.
7:05Oxidation occurs here simultaneously
7:07because the alcohol group at this carbon
7:09atom is oxidized to a keto group, and
7:12decarboxylation occurs simultaneously
7:14for these six molecules of 6-
7:15phosphogluconic acid, and we get six
7:18molecules of CO2.
7:23An important point in this reaction is
7:25that the coenzyme is an NADP molecule,
7:27and in this reaction, a molecule of
7:29reduced NADP is regenerated.
7:32We are now considering the cycle, I
7:34remind you, so we write everything for
7:36six molecules directly. Glucose-6-
7:38phosphate as the starting compound.
7:41And as a result of this stage, we
7:43obtained six molecules of ribulose-5-
7:45phosphate.
7:47All three of these reactions in the
7:49oxidative stage are irreversible.
7:52We also focus our attention on the
7:54regulatory enzymes.
7:57These are glucose-6-phosphate
7:59dehydrogenase and 6-phosphogluconate
8:01dehydrogenase.
8:04Inhibitors. Well, the more regulatory
8:06enzyme is the first one, glucose-6-
8:08phosphate dehydrogenase.
8:11The inhibitors of these enzymes are a
8:13high concentration of reduced NADP and
8:15glucagon, while the activators are
8:17oxidized NADP and insulin.
8:20Let's move on to the characteristics of
8:22the second stage, the non-oxidative
8:24stage. So, what is happening?
8:26Here are our six molecules, or rather,
8:29ribulose-5-phosphate.
8:31They isomerize.
8:33They isomerize.
8:34Their rearrangement takes place. In what
8:37way?
8:38With the help of two enzymes: epimerase
8:41and isomerase.
8:44How does epimerase differ from isomerase
8:46?
8:48In epimerase, there is a direct shift of
8:50the OH group from one position, from the
8:52D-form to the L-form.
8:55For example, we had ribulose-5-
8:57phosphate.
8:59This is a pentose, which is a ketose.
9:02And xylulose-5-phosphate is formed. This
9:05is also a pentose because it has five
9:07carbon atoms, and it is also a ketose.
9:09But how does ribulose-5-phosphate differ
9:12from xylulose-5-phosphate?
9:14By the position of the OH group, right
9:16here at the third carbon atom, and since
9:18they are epimerase, they are epimers of
9:20each other.
9:21And so, epimerase ensures the conversion
9:24of four molecules of ribulose-5-
9:26phosphate into four molecules of
9:28xylulose-5-phosphate. Here are two
9:30molecules and here are two more.
9:33And there is an enzyme, isomerase,
9:35phosphopentoisomerase.
9:37What does isomerase do? We consider
9:39ribulose-5-phosphate, which is a ketose
9:41by nature, containing a keto group.
9:44And ribose-5-phosphate is an aldose,
9:46containing an aldehyde group. These two
9:48compounds are isomers of each other,
9:50meaning ribulose-5-phosphate and ribose
9:53-5-phosphate. So, the isomerase
9:55isomerizes them.
9:57A transition from a keto group to an
9:59aldehyde group occurs, and as a result,
10:02two molecules of ribulose-5-phosphate
10:04are isomerized into two molecules of
10:06ribose-5-phosphate.
10:10Next, the stages, or rather the
10:12reactions, are triggered.
10:15At the heart of this stage are two types
10:17of reactions: the transketolase reaction
10:19and the transaldolase reaction.
10:23The transketolase reaction is a reaction
10:26of transferring these two residues, two
10:28fragments, two carbons, yes, two carbon
10:30atoms, between ketoses and aldoses.
10:36And so, transketolase takes this upper
10:39fragment with two carbon residues, where
10:41the keto group is, which is why it is
10:43called transketolase, and transfers this
10:45residue to the aldose.
10:48So, the next reaction is the interaction
10:51of two molecules of xylulose-5-
10:53phosphate and two molecules of ribose-5
10:55-phosphate.
10:58And this top part from xylulose-5-
10:59phosphate with two carbons is
11:01transferred to the aldehyde group of
11:03ribose-5-phosphate with the help of the
11:05transketolase enzyme.
11:08Here, it is necessary to remember that
11:10the coenzyme is a derivative of vitamin
11:12B1, thiamine diphosphate or thiamine
11:14pyrophosphate.
11:17It stabilizes this very fragment when
11:19the transfer occurs.
11:22Therefore, this is quite important and
11:24must be kept in mind, especially when
11:26preparing for Step 1.
11:29Moving on to the next reaction.
11:32Excuse me. So, as a result, let's go
11:35back once more. Transketolase reaction.
11:38We had the transfer of this fragment
11:39over here.
11:42And as a result, we removed two carbons
11:44and obtained glyceraldehyde phosphate,
11:46which has three carbons.
11:49And here we had five carbons, and a
11:51two-carbon top was added.
11:53We obtained a molecule that has seven
11:55carbons.
11:56This will be sedoheptulose 7-phosphate.
12:00Next is the transaldolase reaction. So,
12:02we have already obtained two products:
12:04glyceraldehyde phosphate, which has
12:06three carbons, and sedoheptulose
12:08phosphate, which has seven carbons.
12:12With the help of the transaldolase
12:14enzyme, the aldehyde fragment is
12:15transferred, because transaldolase
12:17specifically transfers a three-carbon
12:19fragment.
12:22This tip is transferred back to the
12:24glyceraldehyde phosphate.
12:27So, there were three carbons here, this
12:29tip was transferred to the aldehyde
12:31group, adding three more carbons.
12:33And as a result, we obtained two
12:35molecules of fructose 6-phosphate.
12:39And the remainder here is four carbons,
12:41so it will be erythrose 4-phosphate.
12:44These are the products of the
12:46transaldolase reaction. Fructose 6-
12:48phosphate. Two molecules were obtained,
12:50they remain. The next stage is the
12:52following transketolase reaction.
12:56There is an interaction between
12:58erythrose 4-phosphate, which has four
13:00carbons, and two molecules of xylulose 5
13:02-phosphate, which remained from the very
13:04beginning and have five carbons.
13:08And in this transketolase reaction, a
13:10fragment is transferred.
13:12Here we can see we have two carbons.
13:15The coenzyme is thiamine diphosphate, a
13:18derivative of vitamin B1, for
13:20transketolase.
13:21It is transferred from xylulose 5-
13:23phosphate to the erythrose 4-phosphate
13:25fragment.
13:26So, there are four carbons here, and two
13:29are transferred. We obtained a molecule
13:31of fructose 6-phosphate. And here is
13:33xylulose 5-phosphate.
13:36After giving away this top, giving away
13:38two carbons, three carbons remained in
13:40the structure, leaving two molecules of
13:42glyceraldehyde phosphate.
13:46What do we have at the moment? Two
13:47molecules of fructose 6-phosphate. Two
13:50more molecules of fructose 6-phosphate
13:52and two molecules of glyceraldehyde
13:54phosphate.
13:55Next, the following action takes place.
14:00Our two molecules of glyceraldehyde
14:02phosphate condense with each other,
14:04convert into a molecule of fructose 1,6
14:07-bisphosphate, a phosphate group is
14:09cleaved off, and one molecule of
14:10fructose 6-phosphate is formed.
14:16And then these fructose 6-phosphate
14:18molecules that were formed—one, two, and
14:20two more—isomerize into glucose 6-
14:23phosphate molecules.
14:26Thus, at the output, we have obtained
14:28five molecules of glucose 6-phosphate.
14:31And this is how the pentose phosphate
14:33cycle concludes.
14:37We have characterized and completed it.
14:40Now, what is its biological role?
14:42Why are we examining it?
14:45Well, first of all, we have already
14:47understood that as a result of this
14:49cycle, we produce, firstly, we
14:51encountered such a molecule as ribose
14:53phosphate.
14:55So, the first biological role is the
14:57production of ribose 5-phosphate.
15:00Ribose 5-phosphate is necessary for the
15:04synthesis of coenzymes like NAD, FAD,
15:07NADP, and nucleic acids DNA, RNA, and
15:11mononucleotides AMP, GMP, UMP, CMP, TMP
15:14.
15:17And precisely when we examine the
15:19metabolism of purine and pyrimidine
15:21nucleotides, we will use ribose-5-
15:23phosphate.
15:26And you will be asked where we get it in
15:28the human body; it is a result of the
15:30pentose phosphate pathway or the hexose
15:32monophosphate pathway.
15:34Next, the second biological role is the
15:37production of NADPH.
15:39And NADPH is produced for us during the
15:41first stage of this pathway.
15:44And what do we need NADPH for the
15:46synthesis of?
15:47Fatty acids, cholesterol, steroid
15:49hormones, also the synthesis of bile
15:51acids in the liver, and the activation,
15:54or rather the activation of vitamin D3.
15:59It is needed for biotransformation and
16:01the detoxification of various compounds
16:02in the liver.
16:06And most importantly, reduced NADPH is
16:08needed to maintain the antioxidant
16:10defense system for the regeneration of a
16:12tripeptide like glutathione.
16:15And this is very important specifically
16:17for erythrocytes.
16:20Also, intermediate products of the
16:22pentose phosphate pathway can be
16:23included in oxidation pathways and serve
16:26, in essence, as a source of energy for
16:28ATP synthesis.
16:34Now let's look at the biological role of
16:36this pathway in more detail, broken down
16:39by organ.
16:41So, the liver.
16:43The liver is for the production and
16:45direct generation of reduced NADPH.
16:49In order to synthesize lipids and
16:51synthesize cholesterol.
16:53But for the liver, reduced NADPH is
16:55needed for detoxification and for
16:57performing its detoxifying function.
16:59Also, adipose tissue. Here, naturally,
17:01it is the synthesis of lipids.
17:04If we are talking, for example, about
17:06glandular tissues where steroid hormone
17:08synthesis occurs, then it is required
17:10there for the production of these
17:12steroid hormones.
17:14In erythrocytes, the pentose phosphate
17:17pathway—the hexose monophosphate pathway
17:19—is very important because here it
17:21involves the regeneration of glutathione
17:23and the maintenance of antioxidant
17:25defense.
17:26We will talk about erythrocytes later.
17:34Reduced NADPH is extremely important in
17:36phagocytes so that they can perform
17:38their function and so that a so-called "
17:40respiratory burst" occurs to create
17:42reactive oxygen species and to
17:44neutralize and eliminate foreign
17:46bacteria directly.
17:52And in actively dividing cells, such as
17:54bone marrow.
17:57Here, the goal of this pathway is the
17:59production of ribose-5-phosphate in
18:01order to synthesize nucleotides.
18:07Now let's look at the possible pathways
18:09for the progression of this hexose
18:10monophosphate pathway.
18:15That is, each cell has its own specific
18:17needs, and there are peculiarities in
18:19how this pathway proceeds depending on
18:21those needs.
18:23First, the first need is that the cell
18:25requires reduced NADPH and ribose-5-
18:27phosphate.
18:30If we have such a situation in the cell
18:32, for example, a cell that is actively
18:34growing and dividing, then both NADPH
18:36and ribose phosphate are needed.
18:41Then, essentially only the first stage
18:43takes place, because NADPH is being
18:45produced.
18:47We formed the ribose-5-phosphate, and
18:48then the second stage does not occur.
18:51A second option is that mainly ribose-5
18:53-phosphate is needed.
18:56In that case, as a rule, the first stage
18:58might not even occur.
19:02We can have these products of the second
19:04stage, and through reversible reactions
19:06, they convert into ribose 5-phosphate.
19:09There might be a third scenario.
19:11NADPH and energy are needed.
19:14What happens in that case? In the first
19:16stage, NADPH is generated.
19:18The second stage occurs, where
19:20glycolysis intermediates are formed and
19:22these intermediates are channeled into
19:24glycolysis.
19:26Thus, we do not return to the first
19:28stage.
19:29And there might be, for example, a
19:31maximum need for reduced NADP, then this
19:34pathway turns into a cycle, meaning an
19:36oxidative stage occurs, NADPH is
19:38generated, then a non-oxidative stage,
19:40we return to glucose 6-phosphate, and
19:43the oxidative stage happens again. In
19:45other words, there is direct
19:47recirculation, and we are dealing with a
19:49cycle.
19:50This is exactly the cycle we analyzed
19:52when characterizing the pentose
19:54phosphate pathway.
19:58Let’s focus in more detail once again on
20:00the role of the pentose phosphate
20:02pathway in adipose tissue.
20:05So, adipose tissue is for lipid
20:07synthesis. Lipid synthesis is impossible
20:10without reducing equivalents, without
20:12reduced NADPH.
20:14Therefore, the need in adipose tissue
20:16for pentose phosphates and ribose
20:18phosphate is small.
20:20That is why in adipose tissue, this
20:22process, the pathway, has a cyclic
20:24nature. And it is specifically in
20:26adipose tissue that it will be called a
20:28cycle. So, remember that in adipose
20:30tissue, the main focus is the production
20:32of reduced NADPH. Glucose 6-phosphate
20:34enters the first stage.
20:36Ribose 5-phosphate is then formed. Then
20:39the second stage follows. We generate
20:41fructose 6-phosphate, which isomerizes
20:43into glucose 6-phosphate.
20:45And then the first stage happens again,
20:48meaning active production of reduced
20:50NADPH occurs directly.
20:53Let's consider another hexose variant,
20:56when the hexose monophosphate pathway
20:58occurs in a cell that requires both
21:00NADPH and energy.
21:03Then what we call switching occurs.
21:06Why? Because in the pentose phosphate
21:08pathway, the first stage occurs, and
21:10reduced NADPH is generated.
21:12This reduced NADPH is used for the
21:14cell's needs.
21:16And then the products of the second
21:18stage of the pentose phosphate pathway
21:20are included in glycolysis.
21:22And then their oxidation occurs. If
21:24these are aerobic conditions, then
21:26pyruvate is oxidized to acetyl-CoA, and
21:28acetyl-CoA enters the tricarboxylic acid
21:30cycle.
21:33If we see such an integration of the
21:35pentose phosphate pathway into
21:36glycolysis, a close interrelationship
21:38between them, this is typically called a
21:40shunt, as opposed to the cycle in
21:42adipose tissue.
21:46Now let’s look in more detail at the
21:48features of the hexose monophosphate
21:50pathway in erythrocytes.
21:53So, the erythrocyte.
21:56An erythrocyte is a mature cell that no
21:58longer has a nucleus and lacks
21:59mitochondria.
22:01The most important thing is that, in
22:03this case, there are no mitochondria.
22:06Therefore, the main source of energy is
22:08glucose.
22:09Glucose that enters the erythrocyte, as
22:11we already mentioned, is oxidized
22:13anaerobically, and the end product is
22:15lactate. And erythrocytes actively
22:17produce lactate into the blood.
22:19But 90%of the glucose that enters the
22:21erythrocyte goes toward oxidation.
22:24And 10%of the glucose goes to the
22:26pentose phosphate pathway.
22:29What is the significance of the pentose
22:30phosphate pathway for the erythrocyte?
22:33It is extremely important, as it
22:35maintains glutathione in a reduced form
22:38, that is, generating reduced NADPH to
22:40restore glutathione.
22:42Why is reduced glutathione needed in
22:44erythrocytes?
22:46Because it is an antioxidant system.
22:49Because erythrocytes transport oxygen.
22:54They generate quite a few reactive
22:56oxygen species, so a powerful
22:58antioxidant system must work, which
23:00includes glutathione and the enzyme
23:02glutathione peroxidase, for which
23:04reduced glutathione serves as a coenzyme
23:06.
23:10For this antioxidant system to work
23:12effectively, glutathione must be reduced
23:15.
23:16It will fulfill coenzyme functions here
23:18. And for this, there must be reduced
23:21NADPH.
23:23Now, if there is a disruption in the
23:26pentose phosphate pathway in
23:27erythrocytes, the key enzyme of this
23:29pathway, which we analyzed, is glucose-
23:326-phosphate dehydrogenase.
23:35And there may be a deficiency of glucose
23:38-6-phosphate dehydrogenase.
23:40If there is a deficiency of glucose-6-
23:42phosphate dehydrogenase, it leads to a
23:44decrease in the level of reduced NADPH.
23:48As a result, the reduction of
23:50glutathione is impaired.
23:52Furthermore, as a result, reactive
23:54oxygen species accumulate.
23:58And then these reactive oxygen species
24:00can oxidize hemoglobin and damage
24:01erythrocytes.
24:04And consequently, the erythrocyte
24:06membrane.
24:07And as a result, we will see the
24:09destruction of the erythrocyte membrane
24:11and signs of hemolytic anemia.
24:15There is a disease, a hereditary
24:16condition, that is linked to a
24:18deficiency of glucose-6-phosphate
24:20dehydrogenase.
24:22This disease is called favism.
24:24It is X-linked.
24:27If we talk about the manifestations of
24:29this disease, normally, when there is no
24:31stress on the erythrocyte, there are
24:33usually no symptoms.
24:35Why is this? Because a mature
24:37erythrocyte, as we have already said,
24:39does not have mitochondria or a nucleus
24:42.
24:42If there is no nucleus in the cell, then
24:44the realization of genetic information
24:46will not occur in the cell.
24:49That is, the enzyme was synthesized in
24:51the mature erythrocyte.
24:53And this amount of enzymes performs its
24:55functions.
24:56When it is necessary to increase the
24:58production of enzymes, it is impossible
25:00to do so in the erythrocyte. Why?
25:02Because the erythrocyte is already
25:04mature; there is no nucleus.
25:06That is, there is no gene expression,
25:09this chain of DNA, then gene expression
25:11, RNA synthesis, and based on RNA, mRNA
25:14, the synthesis of protein does not
25:16start.
25:17We will not see this realization of
25:19genetic information in a mature
25:21erythrocyte.
25:22Therefore, if there is a deficiency of
25:24glucose-6-phosphate dehydrogenase in,
25:26for example, people or patients, then
25:28under normal conditions, a person may
25:31not even know about it.
25:35But when, for example, a person consumes
25:37certain products or medicines that
25:39produce reactive oxygen species.
25:44These can be beans, for example—that is
25:46exactly why the disease is called favism
25:48.
25:49Specifically, fava beans, these are
25:51special beans that contain biologically
25:54active substances that provoke the
25:55formation of reactive oxygen species.
25:59These are certain medicines.
26:02These can be sulfonamide drugs,
26:04antibiotics, nitrofuran drugs,
26:06analgesics, antipyretics, antimalarials
26:09, or antituberculosis drugs.
26:13And as a result, we see the production
26:15of reactive oxygen species.
26:18And when, for example, there is a
26:20trigger for this oxidative stress, it
26:22arises, and we will see free radical
26:24oxidation reactions being provoked.
26:27And as a consequence, even more reduced
26:30NADPH is needed in order to regenerate
26:32reduced glutathione.
26:34But since there is a deficiency of the
26:36enzyme glucose-6-phosphate dehydrogenase
26:38, as a result, the amount of reduced
26:40NADPH decreases.
26:42That is, normally, there is enough of it
26:44to perform its functions.
26:46But when there is stress on the
26:48erythrocyte, when additional reactive
26:50oxygen species are produced, the
26:52concentration of NADPH is simply
26:53insufficient here.
26:55And then we will see the manifestations
26:57of this pathology.
26:59This is erythrocyte hemolysis, which
27:01subsequently manifests as hemolytic
27:03jaundice because the erythrocytes are
27:05breaking down.
27:07We will see yellowing of the sclera,
27:09eyes, and skin.
27:10There will be dark urine, weakness, and
27:13fatigue.
27:16These are the manifestations of the
27:17disease known as hemolytic jaundice.
27:21Therefore, please pay attention to the
27:23deficiency of this enzyme, glucose-6-
27:25phosphate dehydrogenase.
27:29And as a consequence of that, the
27:30metabolism of the erythrocyte itself is
27:33disrupted, leading to its destruction.
27:37Let us summarize. Thus, the pentose
27:39phosphate pathway is an alternative
27:41pathway for the conversion of glucose-6
27:43-phosphate in the cytosol. It provides
27:45the cell with NADPH and pentose
27:47phosphates, for example, ribose-5-
27:49phosphate.
27:51And here, energy is not directly
27:53generated in this cycle, in this pathway
27:55.
27:55This pathway has two stages: oxidative
27:58and non-oxidative, which perform
28:00different functions.
28:02And the oxidative stage is essentially
28:04the formation of reduced NADP molecules
28:06per glucose molecule.
28:09The non-oxidative stage ensures the
28:11interconversion of pentoses and a
28:12connection with glycolysis. The
28:14operation of the pathway depends on the
28:16needs of the cells.
28:18Ribose phosphate is used for nucleotide
28:20synthesis, and reduced NADPH is used for
28:23the synthesis of fatty acids,
28:24cholesterol, steroid hormones, and
28:26antioxidant defense.
28:29And the key regulatory enzyme is glucose
28:31-6-phosphate dehydrogenase.
28:34It is through this enzyme that the
28:35regulation of the pentose phosphate
28:37pathway occurs.
28:39And it is activated when the level of
28:41oxidized NADP in the cell is low.
28:45When the level of reduced NADPH is high
28:47, it is inhibited instead. And this
28:49pathway is very important in
28:51erythrocytes.
28:5310%of glucose goes specifically to this
28:55pathway because, due to this pathway,
28:57reduced NADPH is formed, which ensures
28:59the reduction of glutathione and the
29:02operation of the antioxidant system.
29:06With a deficiency of glucose-6-
29:07phosphate dehydrogenase in the
29:09erythrocyte, we will see a disruption of
29:12antioxidant defense and, as a result,
29:14erythrocyte hemolysis.
29:16Thank you for being with us.
29:19Like the video, subscribe to our channel
29:21, and write to Alla Ishchenko in private
29:23messages.
29:25And we look forward to seeing you in the
29:27next videos.
29:28Thank you for your attention. Yeah.

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