Biochemistry · Metabolic pathway

Fructose metabolism !

The liver turns fructose from fruit, table sugar and syrups into trioses that enter glycolysis without going through PFK-1.

Updated 2026-11-01

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Balance: ATP -2nadph -1NADH +1

Liver route: fructokinase → fructose 1-phosphate → aldolase B → DHAP + glyceraldehyde → triokinase → glyceraldehyde 3-phosphate.
It bypasses PFK-1, the main control of glycolysis: that is why fructose is metabolised fast and, in excess, favours fat synthesis in the liver.
Polyol pathway (steps 1–2): aldose reductase reduces glucose to sorbitol with NADPH; sorbitol dehydrogenase oxidises it to fructose. This is how seminal fructose is made.
Fructokinase deficiency: essential fructosuria, benign. Aldolase B deficiency: hereditary fructose intolerance, serious.

Fructokinase has no major physiological brake: fructose enters the liver in proportion to the amount eaten.
Aldose reductase works harder the higher the glucose (its Km is high): in diabetes sorbitol builds up in lens, nerves and retina.

Step 1 · Aldose reductase irreversible Glucose + NADPH → Sorbitol + nadpIt reduces glucose to sorbitol (polyol pathway); it matters most when glucose is high.If it fails: Sorbitol built up in lens and nerves contributes to diabetic cataract and neuropathy. Cataract →
Step 2 · Sorbitol dehydrogenase Sorbitol + NAD⁺ ⇌ Fructose + NADHIt oxidises sorbitol to fructose; lens, retina and nerves have little of it, so sorbitol stays there.
Step 3 · Fructokinase (ketohexokinase) irreversible Fructose + ATP → Fructose 1-phosphate + ADPIt phosphorylates fructose on carbon 1 and traps it in liver, kidney and intestine.If it fails: Its deficiency is essential fructosuria: fructose spills into the urine without symptoms. Essential fructosuria →
Step 4 · Aldolase B Fructose 1-phosphate ⇌ Glyceraldehyde + dihydroxyacetone phosphateIt splits fructose 1-phosphate into DHAP, which enters glycolysis directly, and glyceraldehyde.If it fails: Its deficiency is hereditary fructose intolerance: fructose 1-phosphate traps phosphate and halts glycogenolysis and gluconeogenesis. Hereditary fructose intolerance →
Step 5 · Triokinase irreversible Glyceraldehyde + ATP → glyceraldehyde 3-phosphate + ADPIt phosphorylates glyceraldehyde to glyceraldehyde 3-phosphate, which goes on through glycolysis or gluconeogenesis.

In hereditary fructose intolerance fructose 1-phosphate accumulates, phosphate is trapped and ATP and blood glucose fall: hypoglycaemia, vomiting and liver and kidney damage.
Sorbitol crosses membranes poorly and draws in water: it contributes to diabetic cataract, neuropathy and retinopathy.
High intake of added fructose is associated with fatty liver, high triglycerides and high uric acid.

Think of the answer, then tap the question to see it.

Why is fructose metabolised faster than glucose in the liver?

It enters glycolysis as trioses, after PFK-1, and escapes its control.

Which enzyme is missing in essential fructosuria and why is it benign?

Fructokinase; fructose is not phosphorylated, nothing toxic builds up and it leaves in the urine.

Which molecule builds up in hereditary fructose intolerance?

Fructose 1-phosphate, because aldolase B is missing; it traps phosphate and lowers ATP.

Why does sorbitol damage the lens in diabetes?

Aldose reductase makes it from high glucose; the lens has almost no sorbitol dehydrogenase and sorbitol draws in water.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Fructose metabolism (Reactome, 2026); KHK: Ketohexokinase (human) (UniProt, 2026); ALDOB: Fructose-bisphosphate aldolase B (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.