REGULATION OF CYCLIC NUCLEOTIDE METABOLISM

腺苷环化酶的激素控制是由GTP结合蛋白介导的。 通过Gs刺激，通过Gi抑制。一种类似的GTP结合蛋白， 转导蛋白将光受体视紫红质与cGMP偶联 磷酸二酯酶。百日咳毒素，百日咳的病原体， 通过催化ADP-核糖化来灭活胃肠道和转导蛋白 关键的半胱氨酸。百日咳毒素催化的ADP-核糖化 转导蛋白和NAD水解酶受腺嘌呤核苷酸和 磷脂或洗涤剂。NAD水解率增加 通过三磷酸腺苷和洗涤剂或磷脂协同作用；两性离子 洗涤剂CHAPS比非离子洗涤剂Triton X-100更有效 大于溶血磷脂酰胆碱大于磷脂酰胆碱。在……里面 ATP值大于ADP值，AMP值大于AMP值时，CHAPS、NAD水解率升高 大于腺苷；三磷酸腺苷比镁三磷酸腺苷或 非水解性类似物，腺基-5‘-基亚胺二磷酸。GTP和 鸟苷酸-5‘-亚胺基二磷酸的活性低于相应的 腺嘌呤核苷酸。在CHAPS和ATP存在的情况下，活性几乎是 完全依赖二硫苏糖醇。分离的酶(S1) 组分催化NAD的二硫苏糖醇依赖的水解； CHAPS能增强酶的活性，但不能增强ATP的活性。这些研究是一致的 结论是腺嘌呤核苷酸、二硫苏糖醇和CHAPS起作用 在毒素本身而不是在底物上；腺嘌呤核苷酸 似乎与全毒素的激活有关，但与分离的 催化装置。 在动物细胞中，蛋白质的ADP核糖化是一个可逆的过程， 由合成酶和降解酶催化，分别称为 ADP-核糖转移酶和ADP-核糖精氨酸水解酶。具体的 纯化的红细胞水解酶的底物是 α-ADP-核糖精氨酸和α-2‘-磷酸-ADP-核糖精氨酸， 转移酶反应产物。水解酶和转移酶 具有相容的立体特异性和底物专一性 得出结论，这两种酶的活性可能是相反的 ADP-核糖化循环中的ARM。

Hormonal control of adenylate cyclase is mediated by GTP-binding proteins, stimulation via Gs, inhibition via Gi. A similar GTP-binding protein, transducin couples the light receptor rhodopsin to a cGMP phosphodiesterase. Pertussis toxin, an etiologic agent in whooping cough, inactivates Gi and transducin by catalyzing the ADP-ribosylation of a critical cysteine. Pertussis-toxin catalyzed ADP-ribosylation of transducin, and NAD hydrolysis was stimulated by adenine nucleotide and either phospholipid or detergent. NAD hydrolysis was increased synergistically by ATP and detergents or phospholipids; the zwitterionic detergent CHAPS was more effective than the nonionic detergent Triton X-100 greater than lysophosphatidylcholine greater than phosphatidylcholine. In CHAPS, NAD hydrolysis was enhanced by ATP greater than ADP greater than AMP greater than adenosine; ATP was more effective than MgATP or the nonhydrolyzable analogue, adenyl-5'-yl-imidodiphosphate. GTP and guanyl-5'-yl-imidodiphosphate were less active than the corresponding adenine nucleotides. Activity in the presence of CHAPS and ATP was almost completely dependent on dithiothreitol. The isolated enzymatic (S1) component catalyzed the dithiothreitol-dependent hydrolysis of NAD; activity was enhanced by CHAPS but not ATP. The studies are consistent with the conclusion that adenine nucleotides, dithiothreitol, and CHAPS act on the toxin itself rather than on the substrate; adenine nucleotides appear to be involved in the activation of holotoxin but not the isolated catalytic unit. In animal cells, ADP-ribosylation of proteins is a reversible process, catalyzed by synthetic and degradative enzymes known respectively as ADP-ribosyltransferases and ADP-ribosylarginine hydrolases. The specific substrates for a purified erythrocyte hydrolase were Alpha-ADP-ribosylarginine and Alpha-2'-phospho-ADP-ribosylarginine, products of the transferase reaction. The hydrolase and transferases possess a compatible sterospecificity and substrate specificity consistent with the conclusion that the two enzymatic activities may serve as opposing arms in an ADP-ribosylation cycle.