What is the Hexose Monophosphate Shunt (HMS)?
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The HMS (also called HMP or PPP) is an alternative pathway for glucose oxidation that does not consume or generate ATP and occurs in the cytosol of many tissues.
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What is the Hexose Monophosphate Shunt (HMS)?
The HMS (also called HMP or PPP) is an alternative pathway for glucose oxidation that does not consume or generate ATP and occurs in the cytosol of many tissues.
List other names for the Hexose Monophosphate Shunt.
Also called the Hexose Monophosphate Pathway (HMP) and the Pentose Phosphate Pathway (PPP).
Where in the cell does the HMS occur?
The HMS occurs in the cytosol.
Name tissues where the HMS is especially active.
Liver, adipose tissue, red blood cells (RBCs), adrenal cortex, ovaries, testes, retina, and lactating mammary glands.
Does the HMS produce ATP?
No — the HMS is an alternative glucose oxidation route that does not consume or generate ATP.
What are the two main phases of the HMS?
An irreversible oxidative phase and a reversible non-oxidative phase.
What is the key reaction in the oxidative phase of HMS?
Conversion of Glucose-6-Phosphate to Ribulose-5-Phosphate catalyzed by Glucose-6-Phosphate Dehydrogenase (G-6-P-D), producing NADPH + H+.
Which enzyme catalyzes the first and rate-limiting step of the oxidative phase?
Glucose-6-Phosphate Dehydrogenase (G-6-P-D).
What reducing equivalent is produced by the oxidative phase and how many per G6P?
NADPH + H+ is produced; the oxidative phase generates 2 NADPH + H+ per Glucose-6-Phosphate converted.
What happens in the non-oxidative phase of the HMS?
Reversible interconversion of sugars — e.g., Ribulose-5-Phosphate, Fructose-6-Phosphate, Ribose-5-Phosphate, and Glyceraldehyde-3-Phosphate — using transketolase and transaldolase.
Name two enzymes involved in the non-oxidative phase.
Transketolase and transaldolase.
What is Ribose-5-Phosphate used for?
Synthesis of nucleosides, nucleotides, nucleic acids (DNA & RNA), and coenzymes.
Why is NADPH important?
NADPH provides reducing power for reductive biosynthesis (fatty acid and steroid/cholesterol synthesis) and for maintaining reduced glutathione for antioxidant defense.
Give two major biosynthetic processes that require NADPH from HMS.
Fatty acid synthesis and steroid/cholesterol synthesis.
How does the HMS protect red blood cells (RBCs)?
NADPH from HMS maintains reduced glutathione (GSH), which removes H2O2 and protects RBCs from oxidative damage during oxygen transport.
What happens to RBCs when G-6-P-D is deficient?
Reduced NADPH and GSH levels lead to fragile RBCs and hemolysis; patients can develop favism when exposed to oxidizing agents.
What triggers hemolysis in G-6-P-D deficiency (examples)?
Oxidative stress from fava beans, certain infections (viral/bacterial), and drugs such as sulfa drugs, antimalarials (primaquine), and some antipyretics (acetanilid).
What is favism?
An acute hemolytic reaction in G-6-P-D deficient individuals triggered by fava bean ingestion (or other oxidative stresses).
How is G-6-P-D activity regulated by cellular redox state?
NADP+ stimulates G-6-P-D activity, while NADPH + H+ inhibits it (product inhibition).
How do hormones affect HMS enzymes?
Insulin induces G-6-P-D and Phosphogluconate Dehydrogenase during feeding; glucagon represses them during fasting.
What is the Uronic Acid Pathway?
An alternative route of glucose oxidation (cytosolic, mainly in liver) that does not generate ATP and produces UDP-glucuronic acid.
What is UDP-Glucuronic Acid used for?
Conjugation to less polar compounds (e.g., bilirubin, steroids, drugs) to make them more polar and water-soluble for detoxification.
Name other biosynthetic roles of the uronic acid pathway.
Synthesis of mucopolysaccharides (glycosaminoglycans) such as heparin and hyaluronic acid.
Can humans synthesize Vitamin C via the uronic acid pathway?
No — the uronic acid pathway is a precursor for L-ascorbic acid in many animals and plants, but humans cannot synthesize Vitamin C.
Which pathway provides ribose-5-phosphate when nucleotide synthesis demand is high?
The Hexose Monophosphate Shunt (HMS) provides Ribose-5-Phosphate via its oxidative and non-oxidative phases.
If a cell needs more NADPH than ribose-5-phosphate, how does HMS respond?
The oxidative phase produces NADPH; the non-oxidative reactions can recycle sugars back to glycolytic intermediates, allowing continued NADPH production without producing excess ribose-5-phosphate.
Which HMS enzyme is clinically relevant for medication and food sensitivities?
Glucose-6-Phosphate Dehydrogenase (G-6-P-D) — deficiency causes sensitivity to oxidant drugs and foods (favism).
Name two glycolytic intermediates that interconvert with PPP sugars in the non-oxidative phase.
Fructose-6-Phosphate and Glyceraldehyde-3-Phosphate.
Which coenzyme is regenerated by NADPH to maintain antioxidant defenses?
Reduced glutathione (GSH) is maintained by NADPH to detoxify hydrogen peroxide.
Why is the HMS especially important in the adrenal cortex and liver?
These tissues require NADPH for steroid synthesis and other reductive biosynthetic processes, which HMS supplies.
Does the uronic acid pathway generate energy (ATP)?
No — like HMS, the uronic acid pathway does not generate ATP.
Give an example of a drug that may precipitate hemolysis in G-6-P-D deficiency.
Primaquine (an antimalarial) is an example. Sulfa drugs are another class.
Which HMS product is essential for nucleotide and nucleic acid synthesis?
Ribose-5-Phosphate.
What happens to HMS enzyme expression after a meal?
Insulin induces expression of G-6-P-D and Phosphogluconate Dehydrogenase during feeding, increasing pathway activity.
Summarize the main detoxification benefit of the uronic acid pathway.
It forms UDP-glucuronic acid to conjugate and solubilize bilirubin, steroids, and drugs for excretion.
