Dirty Biochemistry Series: HMP Shunt (Pentose Phosphate Pathway)

Overview

The HMP Shunt is also known as the Pentose Phosphate Pathway (PPP).
This lecture is part one of a two-part series.
- Part one focuses on the HMP Shunt.
- Part two will focus on the Glutathione Reductase Pathway.
The HMP Shunt and Glutathione Reductase Pathway work synergistically to manage free radicals in the body.

Primary Objective: Produce NADPH.
Importance of NADPH:
- Required for:
  - Glutathione reduction (covered in part two)
  - Fatty acid synthesis
  - Cholesterol synthesis

Function: Free radical detoxification.
Dependency:
- Reduced glutathione requires NADPH.
- NADPH is produced via the HMP Shunt.

The HMP Shunt begins with glucose-6-phosphate (G6P) from glycolysis.
Instead of continuing to pyruvate, G6P can divert to the HMP Shunt.
Steps of the HMP Shunt:
1. Initial Reactant: G6P is converted into 6-phosphogluconolactone.
2. Key Enzyme: Glucose-6-phosphate dehydrogenase (G6PD).
3. Products: NADPH is generated from NADP+ during the conversion of G6P to 6-phosphogluconolactone.
4. Further Steps: (For completeness) 6-phosphogluconolactone → 6-phosphogluconate → ribulose-5-phosphate.

Location: Occurs in the cytoplasm.
Primary Organs Involved:
- Liver (Hepatic)
- Mammary glands
- Adrenal cortex (Periphery)
Mnemonic: HMP
- H: Hepatic (Liver)
- M: Mammary
- P: Periphery (Adrenal cortex)

The HMP Shunt is crucial for producing NADPH.
Understanding this pathway is critical for examinations (USMLE, COMLEX).
Focus primarily on the conversion of G6P to 6-phosphogluconolactone by G6PD for exams.
These biochemical processes are interconnected and essential for handling free radicals.

The HMP Shunt's production of NADPH is vital for subsequent reactions involving glutathione, which will be discussed in part two.
For a deeper understanding, proceed to the next lecture on Glutathione Reduction.