REGULATION OF CYCLIC NUCLEOTIDE METABOLISM

对腺苷酸敏感的腺苷酸环化酶系统是 细菌毒素通过催化ADP改变其活性， 关键鸟嘌呤核苷酸结合（G）调节的核糖基化 将激素受体与环化酶催化剂偶联的蛋白质 单位 抑制性G蛋白（Gi）被百日咳引起ADP核糖基化 毒素，百日咳的病原体，而 刺激性G蛋白（Gs）被霍乱毒素（CT）ADP-核糖基化 和E.大肠杆菌不耐热肠毒素（LT）， 霍乱和“旅行者腹泻”。 ADP- CT和LT的核糖基转移酶活性被- 19 kDa可溶性和膜鸟嘌呤核苷酸结合蛋白， 称为ADP-核糖基化因子（ARF）;在LT的情况下， 尽管其中两个LT-IIa和LT-IIb有分歧， 在LT-I和CT的氨基酸序列中，参与ARF- 受刺激ADP-核糖基化是保守的。 CT和LT 催化与ADP-核糖基转移酶类似的反应 内源性的动物细胞。 这些ADP-核糖基转移酶 蛋白质中的精氨酸残基以及游离精氨酸。 在动物 组织中，存在ADP-核糖基精氨酸水解酶，其切割ADP-核糖基精氨酸水解酶。 核糖-精氨酸连接，再生精氨酸残基;这些 酶作为39 kDa的单体是有活性的;看来ADP- 核糖基精氨酸水解酶和ADP-核糖基转移酶可以 催化ADP-核糖基化循环的相对臂，类似于 蛋白磷酸化环化酶中的激酶和磷酸酶。 此外，ADP-核糖基精氨酸水解酶，通过逆转 毒素催化的反应，可以促进疾病的恢复。

The hormone-sensitive adenylyl cyclase system is the target of bacterial toxins that alter its activity by catalyzing the ADP- ribosylation of critical guanine nucleotide-binding (G) regulatory proteins that couple hormone receptors to the cyclase catalytic unit. An inhibitory G protein (Gi) is ADP-ribosylated by pertussis toxin, an etiological agent in whooping cough, whereas a stimulatory G protein (Gs) is ADP-ribosylated by cholera toxin (CT) and E. coli heat-labile enterotoxins (LT), etiological agents in cholera and "travelers' diarrhea", respectively. The ADP- ribosyltransferase activities of CT and the LTs are enhanced by - 19 kDa soluble and membrane guanine nucleotide-binding proteins, known as ADP-ribosylation factors (ARFs); in the case of the LTs, it appears that although two of them, LT-IIa and LT-IIb, diverge in amino acid sequence from LT-I and CT, the sites involved in ARF- stimulated ADP-ribosylation have been conserved. CT and LT catalyze reactions similar to those of ADP-ribosyltransferases endogenous to animal cells. These transferases ADP-ribosylate arginine residues in proteins as well as free arginine. In animal tissues, ADP-ribosylarginine hydrolases exist that cleave the ADP- ribose-arginine linkage, regenerating the arginine residues; these enzymes are active as monomers of 39 kDa; it appears that the ADP- ribosylarginine hydrolase and the ADP-ribosyltransferase could catalyze opposing arms of an ADP-ribosylation cycle analogous to the kinases and phosphatases in protein phosphorylation cyclase. In addition, the ADP-ribosylarginine hydrolases, by reversing the toxin-catalyzed reactions, may promote recovery from disease.