In this article we will consider one of the variants of glucose oxidation - the pentose phosphate pathway. Variants of the course of this phenomenon, methods for its implementation, the need for enzymes, biological significance and the history of discovery will be analyzed and described.
Introducing the phenomenon
The pentose phosphate pathway is one of the ways in which C6H12O6 (glucose) is oxidized. Consists of an oxidizing and non-oxidizing stage.
General process equation:
3glucose-6-phosphate+6NADP-à3CO2+6(NADPH+H-)+2fructose-6-phosphate+glyceraldehyde-3-phosphate.
After passing through the oxidative pentose phosphate pathway, the hyceraldehyde-3-phosphate molecule is converted to pyruvate and forms 2 molecules of adenosine triphosphoric acid.
Animals and plants among their subunits have a wide distribution of this phenomenon, but microorganisms use it only as an auxiliary process. All enzymes of the pathway are located in the cellular cytoplasm in animal and plant organisms. In addition, mammals contain these substancesalso in EPS, and plants in plastids, specifically in chloroplasts.
The pentose phosphate pathway of glucose oxidation is similar to the process of glycolysis and has an extremely long evolutionary path. Probably, in the aquatic environment of the Archaean, before the appearance of life in its modern sense, reactions occurred that were precisely of a pentose phosphate nature, but the catalyst for such a cycle was not an enzyme, but metal ions.
Types of existing reactions
As noted earlier, the pentose phosphate pathway distinguishes two stages, or cycles: oxidative and non-oxidative. As a result, on the oxidative part of the pathway, C6H12O6 is oxidized from glucose-6-phosphate to ribulose-5-phosphate, and finally NADPH is reduced. The essence of the non-oxidative stage is to help for the synthesis of pentose and include yourself in the reversible transfer reaction of 2-3 carbon “pieces”. Further, the transfer of pentoses to the state of hexoses can again occur, which is caused by an excess of pentose itself. The catalysts involved in this pathway are divided into 3 enzymatic systems:
- dehydro-decarboxylation system;
- isomerizing type system;
- a system designed to reconfigure sugars.
Reactions with and without oxidation
The oxidative part of the path is represented by the following equation:
Glucose6phosphate+2NADP++H2Oàribulose5phosphate+2 (NADPH+H+)+CO2.
BIn the non-oxidative step, there are two catalysts in the form of transaldolase and transketolase. They accelerate the breaking of the C-C bond and the transfer of carbon fragments of the chain that are formed as a result of this break. Transketolase exploits the coenzyme thiamine pyrophosphate (TPP), which is a vitamin ester (B1) of the diphosphorus type.
General form of the stage equation in the non-oxidative version:
3 ribulose5phosphateà1 ribose5phosphate+2 xylulose5phosphateà2 fructose6phosphate+glyceraldehyde3phosphate.
The oxidative variation of the pathway can be observed when NADPH is used by the cell, or in other words, when it goes to the standard position in its unreduced form.
The use of the glycolysis reaction or the described pathway depends on the amount of NADP concentration+ in the thickness of the cytosol.
Path cycle
Summarizing the results obtained from the analysis of the general equation of the non-oxidative variant pathway, we see that pentoses can return from hexoses to glucose monosaccharides using the pentose phosphate pathway. The subsequent conversion of pentose to hexose is the pentose phosphate cyclic process. The path under consideration and all its processes are concentrated, as a rule, in adipose tissues and the liver. The total equation can be described as:
6 glucose-6-phosphate+12nadp+2H2Oà12(NADPH+H+)+5 glucose-6-phosphate+6 CO2.
Non-oxidative type of pentose phosphate pathway
The non-oxidative step of the pentose phosphate pathway can rearrange glucose withoutremoval of CO2, which is possible due to the enzymatic system (it rearranges sugars and glycolytic enzymes that convert glucose-6-phosphate to glyceraldehyde-3-phosphate).
When studying the metabolism of lipid-forming yeasts (which lack phosphofructokinase, which prevents them from oxidizing C6H12O6 monosaccharides using glycolysis), it turned out that glucose in the amount of 20% undergoes oxidation using the pentose phosphate pathway, and the remaining 80% undergo reconfiguration at the non-oxidative stage of the path. At present, the answer to the question of how exactly a 3-carbon compound is formed, which can only be created during glycolysis, remains unknown.
Function for living organisms
The value of the pentose phosphate pathway in animals and plants, as well as microorganisms is almost the same All cells perform this process in order to form a reduced version of NADPH, which will be used as a hydrogen donor in a reduction-type reaction and hydroxylation. Another function is to provide cells with ribose-5-phosphate. Despite the fact that NADPH can be formed as a result of the oxidation of malate with the creation of pyruvate and CO2, and in the case of dehydrogenation of isocitrate, the production of reductive equivalents occurs due to the pentose phosphate process. Another intermediate of this pathway is erythrose-4-phosphate, which, undergoing condensation with phosphoenolpyruvates, initiates the formation of tryptophans, phenylalanines and tyrosines.
OperationThe pentose phosphate pathway is observed in animals in the organs of the liver, mammary glands during lactation, testes, adrenal cortex, as well as in erythrocytes and adipose tissues. This is due to the presence of active hydroxylation and regeneration reactions, for example, during the synthesis of fatty acids, is also observed during the destruction of xenobiotics in liver tissues and the active oxygen form in erythrocyte cells and other tissues. Processes like these generate a high demand for a variety of equivalents, including NADPH.
Let's consider the example of erythrocytes. In these molecules, glutathione (a tripeptide) is responsible for the neutralization of the active oxygen form. This compound, undergoing oxidation, converts hydrogen peroxide into H2O, but the reverse transition from glutathione to the reduced variation is possible in the presence of NADPH+H+. If the cell has a defect in glucose-6-phosphate dehydrogenase, then aggregation of hemoglobin promoters can be observed, as a result of which the erythrocyte loses its plasticity. Their normal functioning is possible only with the full operation of the pentose phosphate pathway.
The plant's reversed pentose phosphate pathway provides the basis for the dark phase of photosynthesis. In addition, some plant groups are largely dependent on this phenomenon, which can cause, for example, the rapid interconversion of sugars, etc.
The role of the pentose phosphate pathway for bacteria lies in the reactions of gluconate metabolism. Cyanobacteria use this process by virtue oflack of a full Krebs cycle. Other bacteria exploit this phenomenon to expose various sugars to oxidation.
Regulation processes
Regulation of the pentose phosphate pathway depends on the presence of demand for glucose-6-phosphate by the cell and the level of concentration of NADP+ in the cytosol fluid. It is these two factors that will determine whether the aforementioned molecule will enter into glycolysis reactions or into the pentose phosphate type pathway. The absence of electron acceptors will not allow the first steps of the path to proceed. With the rapid transfer of NADPH to NADPH+, the concentration level of the latter rises. Glucose 6 phosphate dehydrogenase is allosterically stimulated and consequently increases the amount of glucose 6 phosphate flux via the pentose phosphate type pathway. Slowing NADPH consumption leads to a decrease in NADP levels+, and glucose-6-phosphate is being utilized.
Historical data
The pentose phosphate pathway began its research path due to the fact that attention was paid to the lack of change in glucose consumption by general glycolysis inhibitors. Almost simultaneously with this event, O. Warburg made the discovery of NADPH and began describing the oxidation of glucose-6-phosphates to 6-phosphogluconic acids. In addition, it was proved that С6Н12О6, marked with 14С isotopes (marked according to С-1), turned into 14СО2 relatively sooner than this the same molecule, but labeled C-6. This is what showed the importance of the process of glucose utilization duringassistance of alternative routes. These data were published by I. K. Gansalus in 1995.
Conclusion
And so, we see that the pathway under consideration is used by cells as an alternative way of oxidizing glucose and is divided into two options in which it can proceed. This phenomenon is observed in all forms of multicellular organisms and even in many microorganisms. The choice of oxidation methods depends on various factors, the presence of certain substances in the cell at the time of the reaction.