Fructose Metabolism & Disorders
| Primary Entry Enzyme: | Fructokinase (Fructose → Fructose-1-Phosphate) |
| Cleavage Key Enzyme: | Aldolase B (Cleaves F1P → DHAP & Glyceraldehyde) |
| Glycolytic Entry Shunt: | Glyceraldehyde-3-Phosphate (Bypasses PFK-1) |
| Alternative Production Path: | Sorbitol Pathway (Glucose → Sorbitol → Fructose) |
High-Yield Core Realities:
- Essential Fructosuria (Fructokinase Defect): Autosomal recessive. Completely benign, asymptomatic condition. Fructose cannot be trapped in cells, accumulates in the blood, and is excreted in the urine. Detected incidentally as a reducing sugar in urine (Clinitest positive, glucose oxidase strip negative).
- Hereditary Fructose Intolerance (Aldolase B Defect): Autosomal recessive. Toxic intracellular trapping of Fructose-1-Phosphate (F1P). F1P accumulation depletes available intracellular inorganic phosphate (Pi), completely halting glycogenolysis and gluconeogenesis.
- HFI Presentation & Triggers: Symptoms appear immediately after **introduction of fruit, juices, or honey** into the infant’s diet (weaning). Presents with severe fasting hypoglycemia, vomiting, jaundice, hepatomegaly, and renal tubular dysfunction.
- The Velocity Secret: Fructose metabolizes much faster than glucose. Because Aldolase B splits F1P downstream of Phosphofructokinase-1 (PFK-1), fructose entry completely **bypasses the rate-limiting step of glycolysis**, driving rapid lipogenesis.
- Sorbitol Pathway Cataract Connection: In tissues with low levels of Sorbitol Dehydrogenase (lens, retina, kidneys, Schwann cells), excess glucose is converted to sorbitol via Aldose Reductase. Sorbitol accumulates osmotically, drawing water into cells and causing cataracts and peripheral neuropathy in diabetic patients.