Ectonucleotide pyrophosphatase/phosphodiesterase 1

Nucleotide diphosphatase ( NPPase ) (more precisely, Ectonukleotid-Pyrophosphatase/Phosphodiesterase ) are called enzymes that catalyze the hydrolytic cleavage of FAD and other dinucleotides. This reaction is important for the degradation of these substances and NPPasen occur in animals and plants. Man has two genes which encode NPPasen: ENPP1 for NPPase 1 (also: PC-1 ), and for ENPP3 NPPase 3 (also CD203c ).

The NPPasen are membrane proteins. The NPPase 1 is mainly found on the surface of plasma cells. NPPase 3, however, is located on the inside of the bile ducts, colon and kidney, prostate, and uterus, as well as on several cancer cell lines. Moreover NPPase 3 is secreted into the blood serum or the lumen of the respective epithelial cell. Exclusively NPPase 3 is also found on basophils and mast cells.

Mutations in the ENPP1 gene can lead to NPPase 1 deficiency and this longitudinal to ossification of the ligamentum posterior ( Olpp ) and infantile arterial calcification ( IIAC ). Overproduction of the enzyme was shown in several tissue types of people with insulin resistance and enzyme variants have been associated in many studies with type 2 diabetes and its complications. The cause is the binding of overproduced NPPase 1 to the insulin receptor and resulting inhibition of signal transduction of insulin. For these reasons NPPase is a pharmaceutical target for the treatment of these diseases.

Catalyzed reactions

NPPasen both are capable of both diphosphatase ( EC 3.6.1.9 ) and as a diesterase ( EC 3.1.4.1 ) to act, and so not only of different dinucleotides such as NAD , NADP , FAD, CoA, and even degrade UDP -glucose, but also triphosphates such as ATP, GTP, CTP, TTP and UTP; also Diadenosinpolyphosphate and cAMP.

H2O AMP

As an example, the cleavage of FAD is shown in FMN and AMP.

Other Features

Through their role in the regulation of the diphosphate content NPPase 1 has a function for bone growth; it also appears at the nucleotide - sugar - metabolism in the ER and in the Golgi apparatus to participate and be a factor in the insulin sensitivity.

Regulation

Both NPPasen be inhibited by low ATP concentration with the following phosphorylation of the enzyme.

Hydrolase Hydrolysis Large intestine Serum (blood) Uridine diphosphate glucose Adenosine triphosphate Guanosine triphosphate Uridine triphosphate Adenosine monophosphate Allergen Digital Object Identifier
611041
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