Metabolism — glycolysis (step 2)
Phosphoglucose isomerase: aldose to ketose
How the Phosphoglucose isomerase works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Glucose 6-phosphate (G6P), PGI (Glu216 base, His388 acid). Conditions: Aqueous, pH ≈ 7.5, 37 °C; reversible, K ≈ 0.5. Bonds formed: C2=O ketone; C1–H₂ (CH₂OH); bonds broken: ring C–O (hemiacetal); C1=O; C2–H. Stereochemistry: cis-enediol(ate) intermediate; enzyme controls the proton transfers. Rate and selectivity: Reversible; Keq about 0.5 at 25 °C.
At a glance
Step 1: Ring opens to the open-chain aldehyde
The enzyme first opens the six-membered glucose-6-phosphate ring to the open-chain aldehyde, using an active-site acid and base. Only the open-chain form can enolize.
Step 2: C2–H removed, C=O protonated: cis-enediol
A base deprotonates C2, and the aldehyde C=O is protonated, giving a cis-enediol(ate) with a C1=C2 double bond. This is the same enediol logic as triose phosphate isomerase, here moving a proton between C1 and C2 on a six-carbon sugar.
Step 3: Reprotonation at C1 gives the ketose
Reprotonation at C1 turns C2 into a ketone, giving fructose-6-phosphate (an aldose-to-ketose isomerization). This sets up the next step because a ketose can be phosphorylated at C1, and later aldolase cleavage then gives two three-carbon pieces.
Abbreviations and terms
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- PFK-1
- Phosphofructokinase-1. The key regulated, committed step of glycolysis.
How it compares with related reactions
| Phosphoglucose isomerase | Enolase | GAPDH | |
|---|---|---|---|
| Reagents | Glucose 6-phosphate (G6P), PGI (Glu216 base, His388 acid) | 2-Phosphoglycerate, 2 Mg²⁺, enolase (Lys345 base, Glu211 acid) | Glyceraldehyde-3-phosphate (G3P), NAD⁺, inorganic phosphate (Pi), GAPDH (Cys149, His176) |
| Conditions | Aqueous, pH ≈ 7.5, 37 °C; reversible, K ≈ 0.5 | Cytosol, pH ≈ 7, 37 °C | Aqueous, pH ≈ 7.4, 37 °C (cytosol) |
| Stereochemistry | cis-enediol(ate) intermediate; enzyme controls the proton transfers | Anti elimination of H and OH; reversible | Hydride delivered to one face of NAD⁺ (pro-R) |
| Rate / selectivity | Reversible; Keq about 0.5 at 25 °C | ΔG°′ ≈ +1.8 kJ/mol; PEP has a very high phosphoryl-transfer potential | Fast and reversible; couples oxidation to phosphate capture |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Phosphoglucose isomerase?
Glucose 6-phosphate (G6P), PGI (Glu216 base, His388 acid). Conditions: Aqueous, pH ≈ 7.5, 37 °C; reversible, K ≈ 0.5.
Which bonds are formed and which are broken?
Formed: C2=O ketone; C1–H₂ (CH₂OH). Broken: ring C–O (hemiacetal); C1=O; C2–H.
What is the stereochemical outcome?
cis-enediol(ate) intermediate; enzyme controls the proton transfers
What controls the rate or the selectivity?
Reversible; Keq about 0.5 at 25 °C
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- Curved-arrow notation: rules and the mistakes students make