The Hexose Monophosphate (HMP) Shunt or Pentose Phosphate Pathway (PPP) is an alternative cytoplasmic pathway of glucose oxidation that generates NADPH and ribose-5-phosphate. NADPH is essential for reductive biosynthesis and antioxidant defense, while ribose-5-phosphate forms the backbone of nucleotides. PPP is crucial for NEET because it integrates metabolism, biosynthesis, and redox balance.
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Another significant pathway in cellular metabolism is the hexose monophosphate shunt pathway, also known as the pentose phosphate pathway (PPP). 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.
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.
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.
The Hexose Monophosphate Shunt pathway takes place in the cytoplasm of cells.
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.
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.
The different phases are:
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.
Key Outputs:
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.
Enzymes Involved:
The enzyme predominant in the non-oxidative pathway is transketolase.
Key Outputs:
Ribose-5-phosphate
Glyceraldehyde-3-phosphate
Fructose-6-phosphate
The functions of the HMP shunt includes:
NADPH is used for:
Fatty acid synthesis
Cholesterol/steroid synthesis
Glutathione regeneration (RBC protection)
Detoxification reactions (cytochrome P450)
Ribose-5-phosphate is needed for:
DNA & RNA synthesis
ATP, NAD⁺, FAD, CoA formation
NADPH maintains reduced glutathione (GSH)
Neutralizes H₂O₂ → H₂O, preventing oxidative injury
The clinical significance is described below-
Glucose-6-Phosphate Dehydrogenase (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 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.
The difference between the three pathways is given in the table below:
Feature | PPP | Glycolysis | ED Pathway |
ATP | 0 | 2 ATP | 1 ATP |
Output | NADPH + R5P | Pyruvate | NADPH + ATP |
Location | Cytosol | Cytosol | Bacteria |
Enzyme | G6PD | PFK-1 | KDPG aldolase |
Function | Biosynthesis, antioxidant | ATP production | Bacterial metabolism |
Important topics for NEET are:
Phases of HMP Shunt
Functions of HMP Shunt
Q1. Who discovered the hexose monophosphate shunt pathway?
Peter Mitchell
Warburg and Dickens
Calvin
Emerson
Correct answer: 2) Warburg and Dickens
Explanation:
The hexose monophosphate shunt, alternatively known as the pentose phosphate pathway (PPP), was discovered in 1938 by Otto Warburg and Franck Dickens. This is an auxiliary pathway parallel to glycolysis and mainly contributes to producing NADPH, as well as ribose-5-phosphate, which is essential in many biosynthetic processes. The discovery was made based on Warburg's oxidation of glucose-6-phosphate experiment, and it greatly contributed to insights into cellular respiration in plants.
Hence, the correct answer is option 2) Warburg and Dickens.
Q2. The hexose monophosphate shunt pathway takes place when there is
Less concentration of NADP
More concentration of NADP
Less concentration of FAD
More concentration of FADH
Correct answer: 2) More concentration of NADP
Explanation:
Hexose monophosphate shunt occurs when the concentration of NADP is higher. The pentose phosphate pathway, sometimes referred to as the hexose monophosphate shunt, is a special pathway that produces substances that the body needs for a variety of purposes. Nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate are produced via the HMP shunt, an alternate pathway to glycolysis.
Hence, the correct answer is option 2) More concentration of NADP.
Q3. The enzyme which converts 6-phosphogluconolactone to 6-phosphogluconate is
Ribulose-5-phosphate isomerase
Transaldolase
Glucose-6-phosphate dehydrogenase
Gluconolactonase
Correct answer: 4) Gluconolactonase
Explanation:
Gluconolactonase is the enzyme that changes 6-phosphogluconolactone into 6-phosphogluconate.
The pentose phosphate pathway includes this reaction, in which gluconolactonase hydrolyzes the lactone ring of 6-phosphogluconolactone to produce 6-phosphogluconate. The pentose phosphate pathway, which produces nucleotides and NADPH and is essential to cellular metabolism, depends on this step to continue.
Hence, the correct answer is option 4)Gluconolactonase.
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Frequently Asked Questions (FAQs)
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 is derived from the Hexose Monophosphate Shunt Pathway during its oxidative phase.
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.
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.
The oxidative phase is the transfer of glucose-6-phosphate to ribulose-5-phosphate. The non-oxidative phase involves interconversion of sugars to yield ribose-5-phosphate, xylulose-5-phosphate, and erythrose-4-phosphate, involving nucleotide synthesis and other metabolic pathways.