From the Research
The Hexose Monophosphate (HMP) Shunt is a critical metabolic pathway that plays a significant role in maintaining cellular homeostasis, and its dysfunction is linked to various disorders, as highlighted in a recent review 1. The HMP shunt serves two primary functions: generating NADPH for reductive biosynthesis and producing ribose-5-phosphate for nucleotide synthesis. NADPH is essential for maintaining reduced glutathione in red blood cells, which protects against oxidative stress by detoxifying free radicals and peroxides. The pathway consists of two phases: the oxidative phase (irreversible) that generates NADPH and the non-oxidative phase (reversible) that produces ribose-5-phosphate. Key enzymes to remember include glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step, and transketolase, which requires thiamine as a cofactor.
Some of the key points to note about the HMP shunt include:
- The HMP shunt is particularly active in RBCs, liver, adrenal cortex, and lactating mammary glands due to their high requirements for NADPH in biosynthetic processes.
- G6PD deficiency is the most common enzyme deficiency worldwide and causes hemolytic anemia when patients are exposed to oxidative stressors like certain medications (sulfonamides, primaquine, dapsone), infections, or fava beans.
- The HMP shunt is also implicated in cancer, with some studies suggesting that metformin, a drug used to treat diabetes, may have anti-cancer properties by targeting the HMP shunt 2, 3, 4, 5.
- Understanding the HMP shunt is crucial for managing patients with disorders related to its dysfunction, and recent studies have highlighted the potential therapeutic targets for treating these conditions 1.