Aldolase

Structure of Aldolase

Identifiers
EC number	4.1.2.13
CAS number	9024-52-6
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Aldolase is an important enzyme in the glycolysis pathway, catalyzing the reversible conversion of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. This reaction is a key step in the metabolic pathway that breaks down glucose to produce energy in the form of adenosine triphosphate (ATP).

Structure

Aldolase is a homotetrameric enzyme, meaning it is composed of four identical subunits. Each subunit has a molecular weight of approximately 40 kDa. The enzyme is highly conserved across different species, indicating its essential role in metabolism. The active site of aldolase contains a lysine residue that forms a Schiff base with the substrate, facilitating the cleavage of the carbon-carbon bond.

Isozymes

There are three main isozymes of aldolase in humans, designated as aldolase A, B, and C. Each isozyme has a distinct tissue distribution and physiological role:

• Aldolase A is predominantly found in muscle and erythrocytes. It plays a crucial role in glycolysis during muscle contraction and in red blood cells.
• Aldolase B is primarily located in the liver, kidney, and intestine. It is involved in both glycolysis and gluconeogenesis, as well as in the metabolism of fructose.
• Aldolase C is mainly expressed in the brain and nervous tissue. It is important for energy production in neurons.

Function

Aldolase catalyzes the fourth step of glycolysis, which is the cleavage of fructose-1,6-bisphosphate into two three-carbon products: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. This reaction is crucial for the continuation of glycolysis, allowing the subsequent steps to proceed and ultimately leading to the production of ATP.

Mechanism

The mechanism of aldolase involves the formation of a Schiff base intermediate between the lysine residue in the active site and the carbonyl group of fructose-1,6-bisphosphate. This intermediate facilitates the cleavage of the C3-C4 bond, resulting in the formation of the two triose phosphates. The reaction is reversible, allowing aldolase to also function in gluconeogenesis.

Clinical Significance

Mutations in the gene encoding aldolase B can lead to hereditary fructose intolerance, a condition characterized by the inability to properly metabolize fructose. This can result in severe hypoglycemia and liver damage if fructose is ingested. Elevated levels of aldolase in the blood can be indicative of muscle damage or liver disease, as seen in conditions such as muscular dystrophy or hepatitis.

Laboratory Measurement

Aldolase activity can be measured in the laboratory using spectrophotometric assays that detect the formation of glyceraldehyde-3-phosphate. These assays are useful in diagnosing muscle and liver diseases.

See Also

• Glycolysis
• Gluconeogenesis
• Fructose metabolism
• Enzyme kinetics

External Links

• Gene information for Aldolase
• UniProt entry for Aldolase A