Hexose Monophosphate (HMP) Shunt: Pathway and Significance

Table of Contents

• Features of the HMP Shunt
• Phases of the HMP Shunt
• Oxidative Phase
• Non-Oxidative Phase
• Significance of HMP Shunt
• Clinical Significance of HMP Shunt
• Frequently Asked Questions

The hexose monophosphate (HMP) shunt, also known as the pentose phosphate pathway or phosphogluconate pathway, is a metabolic pathway that runs parallel to glycolysis. This pathway produces NADPH and intermediates required for the synthesis of nucleic acids and amino acids. Let us study the pathway in detail.

Features of the HMP Shunt

• It is an anabolic pathway that takes place in the cytosol for most organisms. However, in plants, it takes place in plastids.
• The pathway takes place in two distinct phases: oxidative and non-oxidative phases.
• The reactions of this pathway are enzyme catalysed.
• The products obtained from the pathway include NADPH, which is used in biosynthesis in cells, ribose-5-phosphate, which is used in the synthesis of nucleic acid and nucleotides, and erythrose-4-phosphate, which is used for the synthesis of aromatic amino acids.
• In humans, this pathway is most active in mammary glands, adrenal cortex, adipose tissue, erythrocytes, testes and liver.
• The HMP shunt is a tightly controlled metabolic pathway that is connected with other pathways, such as glycolysis and gluconeogenesis, depending upon the metabolic needs of the body.
• Defects in the hexose monophosphate pathway can be linked to several disorders.

Phases of the HMP Shunt

Oxidative Phase

In this phase, NADPH is produced by the reduction of two molecules of NADP⁺. The energy for this production is utilised by the conversion of glucose-6-phosphate to ribulose-5-phosphate. The three steps of the oxidative phase of the HMP shunt are:

• Glucose-6-phosphate is dehydrogenated to 6-phosphoglucono-δ-lactone in the presence of glucose 6-phosphate dehydrogenase. In this reaction, one molecule of NADP⁺ is converted into NADPH.
• 6-phosphoglucono-δ-lactone is hydrolysed into 6-phosphogluconate in the presence of 6-phosphogluconolactonase.
• 6-phosphogluconate is converted into ribulose 5-phosphate in the presence of 6-phosphogluconate dehydrogenase by oxidative decarboxylation.

Non-Oxidative Phase

The non-oxidative phase can be summarised in five steps:

• Ribulose-5-phosphate isomerises into ribose-5-phosphate in the presence of ribose-5-phosphate isomerase.
• Another enzyme, phosphopentose epimerase, isomerises ribulose-5-phosphate into xylulose 5-phosphate at the same time.
• Transketolase enzyme transfers a carbon group from ketose (xylulose-5-phosphate) to the aldose (ribose-5-phosphate), and the products obtained are glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate.
• Transaldolase again transfers a carbon group from sedoheptulose 7-phosphate (ketose) to glyceraldehyde 3-phosphate (aldose), and the products obtained are erythrose 4-phosphate and fructose 6-phosphate.
• A carbon from xylulose 5-phosphate is transferred to erythrose 4-phosphate in the presence of transketolase to obtain glyceraldehyde 3-phosphate and fructose 6-phosphate.

Significance of HMP Shunt

The HMP shunt pathway is significant because it provides NADPH and important intermediated products for the synthesis of biomolecules. Some of the points of significance are:

• NADPH performs several functions in the body, such as:
• It takes part in the synthesis of steroids and fatty acids.
• It is an important component within phagolysosomes in the immune response.
• Glutathione is reduced by NADPH in the presence of glutathione reductase. This helps in quenching free oxygen radicals and peroxides from cells.
• The glyceraldehyde 3-phosphate and fructose 6-phosphate produced in the pathway are intermediates for glycolysis and gluconeogenesis.

Clinical Significance of HMP Shunt

1. Deficiency of Glucose-6-Phosphate Dehydrogenase: The deficiency of this enzyme which is required in the initial steps for the production of NADPH, affects the red blood cells.

Conversely, this deficiency can provide resistance to the malarial parasite Plasmodium falciparum. This is possible because the cell membranes of the RBCs are weakened, and the parasite cannot continue its life cycle.

2. Diagnosis of Thiamine Deficiency: It is diagnosed by administering thiamine to suspected patients and observing the activity of transketolase enzymes in the RBCs. If the enzyme shows high activity, the deficiency of thiamine (vitamin B1) is confirmed.

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