Alkaline Phosphatase

Excerpt

Alkaline phosphatases (ALPs) are a group of isoenzymes located on the outer layer of the cell membrane. They catalyze the hydrolysis of organic phosphate esters found in the extracellular space. Zinc and magnesium are essential cofactors of this enzyme. Despite the diverse tissue distribution and varying physiochemical properties of ALPs, they are classified as true isoenzymes due to their shared ability to catalyze the same reaction.

ALP is found in the cytosol of liver cells and the canalicular membrane of hepatocytes. ALP is found in decreasing concentrations in various organs such as the placenta, ileal mucosa, kidney, bone, and liver. Over 80% of the ALP in serum originates from the liver and bone, with minor contributions from the intestine. Although ALPs are present in various tissues throughout the body, their precise physiological function remains elusive.

ALPs are categorized into 2 types—tissue-specific and tissue-nonspecific. Tissue-specific ALPs are exclusively present in the intestine, placenta, and germinal tissue, specifically within the tissues where they are expressed under physiological conditions. Under specific conditions, the tissue-specific ALPs may also contribute to the circulating pool of serum ALP when there is increased stimulation of their production.

The tissue-nonspecific ALPs are clinically significant, as they constitute most of the circulating fraction in serum. They are encoded by a single gene and expressed in the liver, bone, and kidneys. In contrast, intestinal ALP is coded by a distinct gene separate from the one responsible for placental ALP and the Regan isoenzyme. Excessive amounts of intestinal ALP are produced in Hodgkin lymphoma. Although all tissue-nonspecific ALPs share the identical amino acid sequence, they possess distinct carbohydrate and lipid side chains. These unique physicochemical properties are conferred through post-translational modifications.