Pentose phosphate pathway (PPP) or hexose monophosphate (HMP) shunt

Pentose phosphate pathway (PPP)/Hexose onophosphate (HMP) sunt

  1. Anabolic Function: The PPP is primarily involved in building up molecules, making it an essential anabolic pathway.
  2. Location in Cells: For most organisms, this pathway operates in the cytosol, while in plants, it takes place in plastids.
  3. Two Main Phases: The pathway consists of two key phases:
    • Oxidative Phase: This phase is where NADPH is produced.
    • Non-Oxidative Phase: This phase generates ribose-5-phosphate and other sugars.
  4. Enzyme Involvement: All the reactions in the PPP are driven by specific enzymes that facilitate the processes.
  5. Important Products:
    • NADPH: This molecule is crucial for various biosynthetic activities and helps protect cells from oxidative stress.
    • Ribose-5-Phosphate: This compound is vital for making nucleic acids and nucleotides.
    • Erythrose-4-Phosphate: This is necessary for the production of aromatic amino acids.
  6. Active Tissues: The PPP is particularly active in certain human tissues, such as the mammary glands, adrenal cortex, adipose tissue, red blood cells, testes, and liver.
  7. Regulatory Mechanism: The HMP shunt is tightly regulated, ensuring that it functions according to the body’s metabolic demands.
  8. Connection to Other Pathways: This pathway is interconnected with other metabolic processes, like glycolysis and gluconeogenesis, allowing the body to adjust based on its needs.
  9. Health Implications: Issues with the hexose monophosphate pathway can lead to various health disorders, highlighting its importance in maintaining metabolic health.
  1. Dehydrogenation of Glucose-6-Phosphate: The enzyme glucose-6-phosphate dehydrogenase changes glucose-6-phosphate into 6-phosphoglucono-δ-lactone. During this change, NADP+ is turned into NADPH.
  2. Hydrolysis of 6-Phosphoglucono-δ-Lactone: Next, the enzyme 6-phosphogluconolactonase breaks down 6-phosphoglucono-δ-lactone into 6-phosphogluconate.
  3. Oxidative Decarboxylation: Finally, 6-phosphogluconate is converted into ribulose-5-phosphate by the enzyme 6-phosphogluconate dehydrogenase, which also releases carbon dioxide.
  1. Isomerization to Ribose-5-Phosphate: The enzyme ribose-5-phosphate isomerase converts ribulose-5-phosphate into ribose-5-phosphate, which is essential for synthesizing DNA and RNA.
  2. Formation of Xylulose-5-Phosphate: Meanwhile, another enzyme called phosphopentose epimerase changes ribulose-5-phosphate into xylulose-5-phosphate, allowing for further sugar transformations.
  3. Transketolase Reaction: The enzyme transketolase plays a key role by transferring a two-carbon fragment from xylulose-5-phosphate to ribose-5-phosphate. This reaction produces glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate.
  4. Transaldolase Reaction: Next, the enzyme transaldolase takes a three-carbon fragment from sedoheptulose-7-phosphate and adds it to glyceraldehyde-3-phosphate, resulting in erythrose-4-phosphate and fructose-6-phosphate.
  5. Final Carbon Transfer: In the last step, transketolase acts again, transferring a carbon from xylulose-5-phosphate to erythrose-4-phosphate, leading to the production of more glyceraldehyde-3-phosphate and fructose-6-phosphate.
  1. Makes NADPH: The PPP produces NADPH, which helps the body build fats and cholesterol and protects cells from damage.
  2. Creates Ribose-5-Phosphate: This pathway generates ribose-5-phosphate, necessary for making DNA and RNA, especially in fast-growing cells.
  3. Cell Protection: NADPH helps regenerate glutathione, an antioxidant that protects cells from harmful substances.
  4. Flexibility in Energy Use: The PPP allows cells to switch between making energy and building other important molecules based on their needs.
  5. Sugar Conversion: It helps convert different sugars, which can be used for energy or as building blocks for other molecules.
  6. Supports Rapid Growth: The PPP is very active in tissues that grow quickly, like cancer cells, which need many building blocks.
  7. Understanding Health Issues: Studying the PPP helps us understand certain diseases, like hemolytic anemia, where red blood cells can be damaged.
  1. Cell Protection: The PPP makes NADPH, which helps protect cells from damage. If someone has a G6PD deficiency, their red blood cells can’t make enough NADPH, making them more likely to break down.
  2. Malaria Resistance: People with G6PD deficiency might be less likely to get malaria because their red blood cells are not as good at supporting the malaria parasite.
  3. Thiamine Deficiency Testing: To check for a lack of thiamine (vitamin B1), doctors can give thiamine to patients and test the activity of an enzyme called transketolase in their red blood cells. High activity means there’s a deficiency.

Why is NADPH important?

NADPH plays an important role in a variety of cellular functions, including oxidative stress protection, fatty acid synthesis, and immune system support.

What is G6PD deficiency?

G6PD deficiency is an inherited condition in which the body does not have enough of an enzyme called glucose-6-phosphate dehydrogenase. This can cause issues with red blood cell function, particularly under specific circumstances.

How does the PPP connect with glycolysis?

The PPP interacts with glycolysis via intermediates like : glyceraldehyde-3-phosphate and fructose-6-phosphate, which allows the integration of the metabolism of carbohydrates.