ADP-ribose pyrophosphatase

Bernet D, Pinto RM, Costas MJ et al. Rat liver mitochondrial ADP-ribose pyrophosphatase in the matrix space with low Km for free ADPribose. Biochem J 1994 299(Pt 3) 679-82. 

Figure 8.2. Synthesis of NAD from nicotinamide, nicotinic acid, and qninolinic acid. Quinolinate phosphoribosyltransferase, EC 2.4.2.19 nicotinic acid phosphoribosyl-transferase, EC 2.4.2.11 nicotinamide phosphoribosyltransferase, EC 2.4.2.12 nicotinamide deamidase, EC 3.5.1.19 NAD glycohydrolase, EC 3.2.2.S NAD pyrophosphatase, EC 3.6.1.22 ADP-ribosyltransferases, EC 2.4.2.31 and EC 2.4.2.36 and poly(ADP-ribose) polymerase, EC 2.4.2.30. PRPP, phosphoribosyl pyrophosphate.

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. In Nature (London) 340 680-685 Laugwitz KL, Spicher K, Schultz G et al. (1994) Identification of receptor-activated G proteins selective immunoprecipitation of photolabeled G-protein a subunits. In Methods Enzymol. 237 283-294 Meyer T, Hilz H (1986) Production of anti-(ADP-ribose) antibodies with the aid of a dinucleotide-pyrophosphatase-resistent hapten and their application for the detection of mono(ADP-ribosyl)ated polypeptides. In Ear. J. Biochem. 155 157-165... 

Chambon and coworkers also established the structure of the product as follows. Hydrolysis by snake-venom pyrophosphatase released an isomer of ADP-ribose, as shown in die scheme. This... 

An isomer of "ADP-ribose" obtained after digestion with venom pyrophosphatase. 

It has now been found that the ADP-ribose moiety of nicotinamide adenine dinucleotide is also transferred onto some pro-teins. " When histone serves as an acceptor, several ADP-ribose units are transferred in succession, so that a short chain of oligo-(ADP-ribose), linked covalently to the protein, is formed. In another reaction, transferase II, a soluble enzyme involved in protein synthesis in mammalian cells, acts as an acceptor of a single ADP-ribose unit in the presence of diphtheria toxin. - Treatment of the product with venom pyrophosphatase releases adenosine 5 -monophosphate, but the D-ribose 5-phosphate portion still remains attached to the protein it is, therefore, assumed that the linkage involves C-1 of D-ribose. The transferase II that carries the ADP-ribose unit is completely inactive, but it can be reactivated by incubating with nicotinamide and diphtheria toxin. Under these conditions, the reaction is reversed, generating free transferase II protein and nicotinamide adenine dinucleotide. Thus, diphtheria toxin was shown to have a very specific transglycosylase activity the mechanism of this reaction has been studied in detail. ... 

Figure 1. Metabolism of poly(ADP-ribose). Poly(ADP-ribosyl)ation is a posttranslational modification of acceptor proteins, and poly(ADP-ribose) itself serves as a component of cell struaure. Poly(ADP-ribose) glycohydrolase (PARC) is a main enzyme to degrade poly(ADP-ribose) and forms ADP-ribose as product. Other degrading enzymes ate phosphodiesterase (or pyrophosphatase) and ADP-ribosyl protein lyase.

Nucleosidediphosphatase [Nucleosidediphosphate phosphohydrolase] (3.6.1.6) is produced and catalyzes the reaction A nucleoside diphosphate + H2O = a nucleotide + orthophosphate. [Acts on IDP, GDP, UDP and also on D-ribose 5-diphosphate.] Nucleotide pyrophosphatase [Dinucleotide nucleotidohydrolase] (3.6.1.9) is produced and catalyzes the reaction A dinucleotide + H2O = 2 mononucleotides. [Substrates include NAD" " NADP ", FAD, CoA and also ATP and ADP.] Deoxycytidinetriphosphatase [dCTP nucleotidohydrolase, Deoxy-CTPase, dCTPase] (3.6.1.12) is produced and catalyzes the reaction dCTP + H2O = dCMP + pyrophosphate. [Also hydrolyses dCDP to dCMP and orthophosphate]... 

---