Pentose Phosphate Pathway Overview

Pentose Phosphate Pathway

• Also known as the hexose monophosphate shunt (HMP shunt)
• A metabolic pathway that is a bypass around the first stage of glycolysis.
• Occurs in the cytosol of all cells.

Functions

• Produces reducing power in the form of NADPH.
• Generates ribose 5-phosphate for nucleotide synthesis.

Overview

• Involves 2 irreversible oxidative reactions, followed by reversible sugar-phosphate interconversions.
• Has 2 branches: an irreversible oxidative branch and a reversible non-oxidative branch.

3 Reactions

• 1. Dehydration of glucose 6-phosphate to 6-phosphogluconolactone: This reaction is catalyzed by glucose 6-phosphate dehydrogenase (G6PD), using NADP+ as a coenzyme. NADPH is a potent inhibitor of G6PD, and insulin upregulates G6PD gene expression.

• 2. Formation of ribulose 5-phosphate: 6-phosphogluconolactone is hydrolyzed to 6-phosphogluconate, which then undergoes oxidative decarboxylation to produce ribulose 5-phosphate. This reaction is facilitated by 6-phosphogluconate dehydrogenase.

• (Additional information on specific enzymes and the overall reaction process is found on page 4 of the document).

Main Advantages

• Liver, mammary glands, and adipose tissue: active in NADPH-dependent fatty acid biosynthesis.
• Testes, ovaries, placenta, and adrenal cortex: active in NADPH-dependent steroid hormone biosynthesis.
• Red blood cells: rely on NADPH to maintain reduced glutathione, critical for cellular redox balance.

Reversible Non-oxidative Reactions

• Occurs in cells synthesizing nucleotides and nucleic acids.
• Catalyzes the interconversion of sugars containing 3-7 carbons.
• Enables the conversion of ribulose 5-phosphate into ribose 5-phosphate (for nucleotide synthesis) or glycolysis intermediates (fructose 6-phosphate and glyceraldehyde 3-phosphate).

Main Enzymes

• The primary enzymes involved in non-oxidative reactions are transaldolase and transketolases.
• Thiamine pyrophosphate (TPP) is crucial for the function of these enzymes, as well as pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (aKGDH).

Cell Needs and NADPH/R5P

• If the cell requires NADPH but not ribose 5-phosphate, ribulose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate, which then enter glycolysis.
• When the cell needs more ribose 5-phosphate than NADPH, fructose 6-phosphate and glyceraldehyde 3-phosphate are converted into ribose 5-phosphate.

Most Important Products

• NADPH: essential for various reductive biosynthetic processes, including fatty acid synthesis.
• Ribose 5-phosphate: used for the synthesis of RNA, DNA, NAD+, FAD, ATP, and coenzyme A.

Uses of NADPH

• Reductive biosynthesis: plays a crucial role in the synthesis of fatty acids, cholesterol, steroid hormones, and bile salts.
• Reduction of hydrogen peroxide: helps detoxify reactive oxygen species (ROS).
• Cytochrome P450 monooxygenase system: involved in the metabolism of various substances, including drugs and steroids.
• Phagocytosis by white blood cells: supports the activity of phagocytic cells that engulf and destroy pathogens.
• Nitric oxide synthesis: required as a co-factor for nitric oxide synthases.

Glucose 6-Phosphate Dehydrogenase Deficiency

• The most common disease-producing enzyme abnormality among humans.
• Deficiency results in reduced NADPH production in erythrocytes, leading to hemolytic anemia.Oxidative stress, certain drugs, and infections can trigger acute hemolytic crises in individuals with G6PD deficiency.
• G6PD deficiency is caused by various mutations in the gene that codes for the enzyme.

Explore the Pentose Phosphate Pathway, also known as the hexose monophosphate shunt. This quiz covers its functions, key reactions, and the role of NADPH in cellular metabolism. Learn about its two branches and the biochemical processes involved.