hexose monophosphate shunt pathway: Steps, Diagram, Uses

Edited By Irshad Anwar | Updated on Aug 27, 2024 03:14 PM IST

Definition Of Hexose Monophosphate Shunt Pathway

Another significant pathway in cellular metabolism is the hexose monophosphate shunt pathway, also known as the pentose phosphate pathway. It is an important process for the formation of nicotinamide adenine dinucleotide phosphate, a key means of reducing power for biosynthetic reactions and cellular redox balance, and ribose-5-phosphate for nucleotide and nucleic acid synthesis.

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The PPP is a cytoplasmic process subdivided into two major phases: an oxidative phase that produces the reduced co-factor NADPH, and a non-oxidative phase that yields ribose-5-phosphate and other sugars. In addition to having several important anabolic applications, this pathway substantially enhances the capacity of the cell for redox homeostasis and, therefore, in more general terms, metabolic plasticity and cell health.

Importance In Cellular Metabolism

This PPP, besides providing cells both with the reducing power and essential metabolic intermediates, also provides NADPH in anabolic processes like the biosynthesis of fatty acids, cholesterol, and detoxification of reactive oxygen. The requirement of ribose-5-phosphate in nucleotide biosynthesis is extremely vital for cell growth and repair. Hence, the pathway supports cell functions and growth, especially in tissues exhibiting high biosynthetic activity or oxidant stress.

Location And Occurrence

The Hexose Monophosphate Shunt pathway takes place in the cytoplasm of cells.

Cellular Location Of The Pathway

Unlike glycolysis, which also occurs in the cytoplasm, the PPP can function independently, even though it is in association with glycolytic and several other metabolic pathways.

Tissues And Organs Where The Pathway Is Predominantly Active

This pathway is very active in tissues with wide biosynthetic requirements and high oxidative stress, like the liver, adipose tissue, adrenal glands, and red blood cells. These tissues use the PPP to fulfil their requirements for NADPH and ribose-5-phosphate.

Phases Of The Pathway

The different phases are:

Oxidative Phase

Enzymes Involved

The important enzymes in the oxidative phase of this pathway are composed of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconactonase, and 6-phosphogluconate dehydrogenase.

Production of NADPH and Ribulose-5-Phosphate

This reaction will convert glucose-6-phosphate into ribulose-5-phosphate and will aid in the generation of NADPH. The generation of NADPH is for reductive biosynthesis and, at the same time, removes oxidative stress.

Non-Oxidative Phase

Enzymes Involved:

The enzyme predominant in the non-oxidative pathway is transketolase

Clinical Significance

The clinical significance is described below-

Disorders Associated With The Pathway

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

G6PD deficiency is a common genetic disorder that impacts the oxidative phase of the PPP. The lack of formation of NADPH can lead to a reduction in red blood cells' ability to withstand oxidative stress with the administration of certain drugs or during infections, thus resulting in hemolytic anaemia.

Implications in Hemolytic Anemia

Decreased generation of NADPH by the cells compromised the integrity of red cells in G6PD-deficient patients, leading to their lysis and consequent anaemia.

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Frequently Asked Questions (FAQs)

1. What is the main purpose of the Hexose Monophosphate Shunt Pathway?

The Hexose Monophosphate Shunt Pathway also referred to as the Pentose Phosphate Pathway, PPP, serves the production of NADPH and ribose-5-phosphate as its main functions. NADPH supplies the reducing power for anabolic reactions, for instance, in lipid and nucleotide syntheses, and simultaneously provides the cells with defensive effects against oxidative stress by reducing reactive oxygen species. Ribose-5-phosphate is an important precursor in the biosynthesis of nucleotides and nucleic acids.

2. How is NADPH produced in the Hexose Monophosphate Shunt Pathway?

NADPH is derived from the Hexose Monophosphate Shunt Pathway during its oxidative phase. In this course, glucose-6-phosphate is oxidised to 6-phosphogluconolactone by the action of the enzyme Glucose-6-phosphate dehydrogenase (G6PD). This lactone is hydrolysed to 6-phosphogluconate, which is subjected to decarboxylation by 6-phosphatase.

3. What are the consequences of G6PD deficiency?

G6PD deficiency causes a defect for the body in the production of NADPH, which is very important for the body in times of need for a reducing equivalent. So an individual who is affected has a decreased capability of controlling oxidative stress and is affected by hemolytic anemia. These may be triggered by infections, some medications or dietary intake of certain foods, including fava beans, that bring about an increase in oxidative stress, which brings about the early destruction of red blood cells.

4. How is the Hexose Monophosphate Shunt Pathway regulated?

The key controller of the hexose monophosphate shunt pathway is the availability of glucose-6-phosphate and, indirectly, the activity of the first committed enzyme of this pathway, i.e. glucose-6-phosphate dehydrogenase (G6PD) because G6PD is a sensitive enzyme inhibited by the cellular levels of NADPH.

When the levels of NADPH reach a higher concentration in a cell, the activity of the enzyme gets depressed so that snap-flux passes in the direction of the oxidative phase of the pathway. Other control mechanisms relate to the demands of the whole cell and the production of NADPH and ribose 5-phosphate.

5. What is the difference between the oxidative and non-oxidative phases of the pathway?

The oxidative phase of the Hexose Monophosphate Shunt Pathway is NADPH-producing and consists of three enzymes: glucose-6-phosphate dehydrogenase, 6-phosphogluconolactonase, and 6-phosphogluconate dehydrogenase. This oxidative step is the transfer of glucose-6-phosphate to ribulose-5-phosphate.

The non-oxidative phase involves transketolase and transaldolase enzymes for the interconversion of sugars to yield ribose-5-phosphate, xylulose-5-phosphate, and erythrose-4-phosphate, involving nucleotide synthesis and other metabolic pathways.