Aldolase

Aldolase is a glycolytic enzyme that catalyzes the reversible cleavage of fructose-1,6-bisphosphate (FBP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). This step provides the two triose phosphates that proceed through subsequent energy-yielding reactions in glycolysis, and it can operate in the reverse direction during gluconeogenesis when cellular conditions favor synthesis of FBP.

There are two mechanistic classes of aldolase. Class I aldolases are ly-sine–dependent enzymes that form a Schiff base intermediate with the substrate, while class II aldolases are zinc-dependent metalloenzymes that use a metal ion to stabilize reaction intermediates. Class I enzymes primarily occur in animals, plants, and many bacteria and typically function as tetramers; class II enzymes are found in various organisms and often function as dimers.

In humans and many other organisms, the aldolase family includes three cytosolic isozymes produced by separate genes: ALDOA (aldolase A), ALDOB (aldolase B), and ALDOC (aldolase C). They exhibit tissue distribution differences, with ALDOA most abundant in muscle, ALDOB in liver and kidney, and ALDOC in brain and retina, although all can be present to varying extents in multiple tissues.

Clinical and practical significance includes the association of aldolase B deficiency with hereditary fructose intolerance, a metabolic disorder caused by impaired processing of dietary fructose. Measurement of aldolase activity can also aid in diagnosing muscle or liver pathology, reflecting tissue damage or metabolic disturbances. In addition to its metabolic roles, aldolase has been noted to participate in noncanonical cellular functions in some contexts.