aldoláza

Aldolase is a glycolytic enzyme that catalyzes a key reversible reaction in carbohydrate metabolism: the cleavage of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). The same enzyme can also catalyze the reverse aldol condensation, linking GAP and DHAP to form fructose-1,6-bisphosphate. In humans, aldolases are cytosolic enzymes that participate primarily in glycolysis and, indirectly, in gluconeogenesis.

Two mechanistic classes of aldolases exist. Class I aldolases form a Schiff base between the substrate and an active-site lysine, while class II enzymes are metal-dependent, typically requiring a divalent cation such as zinc to stabilize reaction intermediates. In humans, the three cytosolic aldolase isoforms—A, B, and C—are generally categorized as class I enzymes.

Isoforms and tissue distribution

- Aldolase A: widespread in muscle and leukocytes; important for high-energy-demand tissues.

- Aldolase B: highly expressed in liver, kidney, and intestine; deficiency causes hereditary fructose intolerance due to impaired metabolism of fructose-1-phosphate.

- Aldolase C: enriched in brain and, to a lesser extent, other tissues.

Structure and localization

Aldolase typically forms oligomeric assemblies, commonly functioning as homotetramers in mammalian cells, and resides in the cytosol where glycolysis occurs.

Clinical relevance

Defects in aldolase activity lead to metabolic diseases. Aldolase B deficiency causes hereditary fructose intolerance, presenting with hypoglycemia, vomiting, and liver dysfunction after fructose ingestion. Aldolase A deficiency is associated with rare congenital myopathy and non-spherocytic hemolytic anemia, often triggered by stress or fever.

Overall, aldolase is a essential, conserved enzyme bridging glycolysis and energy production, with multiple isoforms reflecting tissue-specific demands.