fructokinase

**Reaction:** Fructose + ATP → fructose-1-phosphate + ADP (fructokinase, also called ketohexokinase). Fructose-1-phosphate is then cleaved by aldolase B into DHAP and glyceraldehyde. Glyceraldehyde is phosphorylated by triose kinase to glyceraldehyde-3-phosphate. DHAP and glyceraldehyde-3-phosphate then enter glycolysis or gluconeogenesis.

**Key features:** - Location: liver (main site), kidney, small intestine mucosa. - It bypasses PFK-1, the main regulatory step of glycolysis. Fructose metabolism is therefore not regulated by insulin or by feedback inhibition. This allows rapid flux into pyruvate, acetyl-CoA, and fatty acid and triglyceride synthesis. High fructose intake (for example, high-fructose corn syrup) is linked to hepatic steatosis, hypertriglyceridemia, and uric acid production. - Fructokinase uses ATP rapidly and has no feedback regulation. Large fructose loads can deplete ATP and phosphate, which raises AMP and drives uric acid production. - Other tissues, such as adipose tissue and muscle, use hexokinase to phosphorylate fructose to fructose-6-phosphate. Hexokinase has a much lower affinity for fructose than for glucose.

**Essential fructosuria (fructokinase deficiency):** - Autosomal recessive and benign. - Fructose is not trapped in cells, so it accumulates in the blood and appears in the urine. - It is asymptomatic. It is usually found incidentally when urine tests are positive for reducing sugar (Benedict's or Clinitest) but negative on glucose oxidase dipstick. - No treatment is needed.

**Comparison with related disorders:** - Hereditary fructose intolerance (aldolase B deficiency): autosomal recessive. After fructose, sucrose, or sorbitol exposure (often at weaning), fructose-1-phosphate accumulates and sequesters phosphate. This inhibits glycogenolysis and gluconeogenesis. Findings are hypoglycemia, vomiting, jaundice, hepatomegaly, hepatic failure, and renal tubular dysfunction. Treatment is to avoid fructose, sucrose, and sorbitol. - Galactosemia (classic GALT deficiency): cataracts, jaundice, and E. coli sepsis in infants. Galactokinase deficiency causes only cataracts and galactitol accumulation.

**High-yield pearls:** - Fructokinase deficiency: no symptoms and no phosphate trapping. Aldolase B deficiency: severe symptoms. - Both fructose disorders can produce a positive urine reducing substance test. - Sorbitol is converted to fructose by sorbitol dehydrogenase (liver, ovaries, seminal vesicles). Aldose reductase converts glucose to sorbitol, and tissues lacking sorbitol dehydrogenase (lens, retina, Schwann cells, kidney) accumulate sorbitol. This contributes to diabetic cataracts and neuropathy.