ALDOB

The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is one of a group of three aldolase enzymes that are responsible for breaking down certain molecules in cells throughout the body. Four identical aldolase B enzymes need to be attached (bound) to each other in a four-enzyme unit called a tetramer to work.

Aldolase B is found primarily in the liver, but it is also present at lower levels in kidney and intestinal cells. Aldolase B is involved in the breakdown (metabolism) of the simple sugar fructose, which is found mostly in fruits and is used in the body for energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate. To a lesser degree, aldolase B is also involved in the breakdown of the simple sugar glucose.

The metabolism of fructose is not only essential for the body to use this sugar as energy, but the molecules produced from its breakdown are also needed in the body. The breakdown of dihydroxyacetone phosphate releases a phosphate group (a cluster of oxygen and phosphorus atoms) from this molecule. These phosphate groups are eventually re-used for a number of cell processes, including in the production of adenosine triphosphate (ATP), the cell's main energy source, and the release of stored sugar in the liver.

hereditary fructose intolerance - caused by mutations in the ALDOB gene

More than 50 mutations in the ALDOB gene have been found to cause hereditary fructose intolerance, a condition characterized by nausea and intestinal discomfort following ingestion of foods containing fructose. Most of these mutations replace single protein building blocks (amino acids) in the aldolase B enzyme and result in the production of an enzyme with reduced function. A mutation found in approximately half of people with hereditary fructose intolerance replaces the amino acid alanine with the amino acid proline at position 149 in the enzyme (written as Ala149Pro or A149P). This mutation alters the 3-dimensional shape of the enzyme. Alteration of the shape of the enzyme makes it difficult for the aldolase B enzymes to bind together and form tetramers. If it is not in a tetramer, aldolase B cannot metabolize fructose.

A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. In addition, fructose-1-phosphate does not release the phosphate groups needed for continued ATP production and the regulation of stored sugar. The death of liver cells and reduced number of phosphate groups lead to hypoglycemia, liver dysfunction, and other features of hereditary fructose intolerance.