5'-nucleotidase

InterPro Family

5′ Nucleotidase (EC 3.1.3.5) is an enzyme which catalyzes the phosphorylytic cleavage of 5′ nucleotides. Although originally found in snake venom, the activity of 5'nucleotidase has been described for bacteria and plant cells, and is widely distributed in vertebrate tissue. In mammalian cells the enzyme is predominantly located in the plasma membrane and its primary role is in the conversion of extracellular nucleotides (e. g. 5' AMP), which are generally impermeable, to the corresponding nucleoside (e. g. adenosine) which can readily enter most cells. Consequently, the enzyme plays a key role in the metabolism of nucleotides. The enzyme has a wide substrate specificity for nucleotides and has been shown to hydrolyze 5'nucleotides rapidly, ribose 5 phosphate slowly, and other phosphate esters extremely slowly (if at all). The enzyme catalyses the following reaction:

a 5′ nucleotide + H2O a nucleoside + phosphate

The 5′ nucleotidase catalyzed reaction of an AMP nucleotide to adenosine nucleoside is shown below:

Studies of the soluble form of human ecto 5′ nucleotidase, without a GPI anchor, have shown that the C terminal domain holds the substrate binding pocket, and that the aromatic purine motif of the substrate is stacked between two phenylalanine residues. In other words, the test is used to determine if elevated protein levels are due to skeletal damage or liver damage. Elevated levels may indicate cholestasis, destruction of liver cells, hepatitis (liver inflammation), liver ischemia, a liver tumor, or use of liver damaging drugs. Pregnancy and certain medications (acetaminophen, halothane, isoniazid, methyldopa, nitrofurantoin) may interfere with the test.

Ecto 5'Nucleotidase is considered a maturation marker for T cells and B cells. This is due to the fact that the enzyme activity is approximately 10 times higher for peripheral T cells than thymocytes, 5 6 times higher in adult peripheral B cells than fetal B cells, and largely absent in non T cell and non B cell lymphocytes. In immunodeficiency diseases with arrested lymphocyte maturation, ex 5'nucleatidase activity is generally low.

Numerous studies have shown that erythrocyte pyrimidine 5′ nucleotidase activity is significantly lowered in patients with lead poisoning, and that pyrimidine 5′ nucleotidase activity can be used as an index of lead poisoning. It is believed that lead induced deficiency of the enzyme in maturing erythroid cells is responsible for basophilic stippling and hemolysis in a manner analogous to the pathogenesis of the hereditary enzyme deficiency syndrome. The mechanism of inhibition of 5'nucleotidase in lead poisoning may contribute to the hemolytic syndromes that occur in patients with acute lead poisoning.

Cytosolic 5 nucleotidase II superactivity has been associated with autism spectrum disorder via a disorder of carnitine biosynthesis.