Hepatic-dominant fructose handling, distinct from glycolysis. Fructose → fructose-1-P (fructokinase / ketohexokinase, KHK — bypasses the insulin-sensitive PFK-1 step). F1P → glyceraldehyde + DHAP (aldolase B). Glyceraldehyde → glyceraldehyde-3-P (triokinase) → glycolysis. Bypass of PFK-1 makes fructose uniquely lipogenic at high intakes — drives hepatic de novo lipogenesis (see fatty_acid_biosynthesis) + NAFLD risk. Hereditary fructose intolerance = aldolase B deficiency (autosomal recessive): F1P accumulates, depletes ATP + phosphate, produces hypoglycemia + vomiting + hepatic injury after fructose / sucrose / sorbitol exposure. Essential fructosuria = benign fructokinase deficiency (no symptoms — fructose excreted unchanged).
Organ Systems
digestive
endocrine
Pathway Steps
fructose → fructose-1-phosphate — via fructokinase (KHK) — hepatic; bypasses PFK-1. Hepatic fructokinase (KHK) phosphorylates fructose without the feedback that governs glucose, bypassing rate-limiting PFK-1 — so a fructose load floods downstream glycolysis/lipogenesis unchecked and transiently depletes ATP/Pi, raising uric acid. Central to fructose’s metabolic effects.
fructose-1-phosphate → glyceraldehyde-dhap — via aldolase B — HEREDITARY FRUCTOSE INTOLERANCE deficiency. Aldolase B cleaves fructose-1-phosphate; its deficiency causes hereditary fructose intolerance, where fructose-1-phosphate accumulates, sequesters phosphate, and triggers hypoglycemia and liver injury on fructose ingestion.
glyceraldehyde-dhap → glyceraldehyde-3-phosphate — via triokinase; enters glycolysis below PFK-1. Triokinase phosphorylates glyceraldehyde to join glycolysis below PFK-1; the DHAP produced is also a precursor for glycerol-3-phosphate and triglyceride synthesis — the lipogenic exit linking high fructose intake to hepatic fat.