Hexose Monophosphate (HMP ) Shunt

The Hexose monophosphate pathway (HMP) or pentose phosphate pathway (PPP) is a metabolic pathway parallel to Glycolysis which generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-phosphate.

1.0Introduction

The (HMP) hexose monophosphate pathway, also known as the pentose phosphate pathway or the phosphogluconate pathway, is an alternative metabolic pathway that runs parallel to glycolysis. It occurs in the cytoplasm of most cells and involves a series of reactions that serve multiple purposes in the cell's metabolism. It involves the oxidation of glucose-6- phosphate to 6-phosphogluconic acid which in turn is converted into pentose phosphate.

2.0Phases of HMP Shunt

The pathway consists of two phases: the oxidative phase and the non-oxidative phase. The oxidative phase involves NADPH generation and the conversion of glucose-6-phosphate to ribose-5-phosphate. The non-oxidative phase involves interconversions of various sugars to produce ribose-5-phosphate and other metabolites.

Steps involving in Oxidative phase :

1. Glucose-6-phosphate is oxidized to 6-phosphogluconolactone by the enzyme glucose-6-phosphate dehydrogenase. This reaction generates NADPH and occurs in the presence of NADP+.
2. 6-Phosphogluconolactone is converted to 6-phosphogluconate by the enzyme 6-phosphogluconolactonase.

3. In this step, 6-phosphogluconate is oxidatively decarboxylated to produce ribulose-5-phosphate, carbon dioxide, and another molecule of NADPH, through the action of the enzyme 6-phosphogluconate dehydrogenase.

Steps involving in non-oxidative phase : 

1. Ribulose-5-phosphate converted into ribose-5-phosphate by the help of pentose phosphate isomerase at the same time another enzyme named pentose phosphate epimerase convert ribulose-5-phosphate into xylulose-5-phosphate. 
2. In this step xylulose-5-phosphate and ribose-5-phosphate combine in the presence of transketolase enzymes to form glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate.
3. In the next step Sedoheptulose-7-phosphate and  glyceraldehyde-3-phosphate combine with the help of transaldolase enzyme, resulting in the formation of erythrose-4-phosphate and fructose-6-phosphate.
4. Now erythrose-4-phosphate reacts with xylulose-5-phosphate in the presence of transketolase to form fructose-6- phosphate and  glyceraldehyde-3-phosphate. 
5. In the presence of enzyme phosphohexose isomerase, fructose-6-phosphate is converted into glucose-6-phosphate.

6. In the last 6 molecules of glucose-6-phosphate after oxidation produce 6 molecules of CO₂ and 5 molecules of glucose-6-phosphate are regenerated and 12 molecules of NADP⁺ is converted into 12 molecules of NADPH. 

6 Glucose-6-phosphate + 12 NADP⁺ + 7 H₂O → 5 Glucose-6-phosphate + 6 CO₂ + Pi + 12 NADPH 

3.0Overview of HMP Shunt

4.0Significance of HMP Shunt

1. It generates NADPH molecules which are used as reductants in biosynthetic processes under conditions when NADPH molecules are not generated by photosynthesis. It is therefore especially important in non-photosynthetic tissues such as in differentiating tissues, germinating seeds and during periods of darkness. Production of NADPH is not linked to ATP generation in the pentose phosphate pathway.
2. The pathway produces pentose sugars, including ribose-5-phosphate, which is a vital precursor for nucleotide biosynthesis. Nucleotides are the building blocks of DNA and RNA.
3. It plays an important role in fixation of CO₂ in photosynthesis through Ribulose-5-Phosphate (Ribulose 1, 5-bisphosphate (RuBP) derived from Ribulose-5-Phosphate (RuMP)  is the primary acceptor of CO₂, in photosynthesis).
4. This pathway is involved in the production of several intermediate compounds, including ribose-5-phosphate, erythrose-4-phosphate, and glyceraldehyde-3-phosphate. These intermediates are essential for the synthesis of nucleotides and other important biomolecules in the cell.
5. The HMP shunt is interconnected with other metabolic pathways, like glycolysis and the citric acid cycle, playing a critical role in the overall metabolic network of the cell.