Navarro A, Grisolía S
Eur J Biochem. 1985 May 15;149(1):175-80. doi: 10.1111/j.1432-1033.1985.tb08908.x.
Ornithine transcarbamoylase (OTC) is inactivated by liver lysosomes. Carbamoyl phosphate prevents the inactivation of OTC by lysosomes, while ATP, ADP, GTP, GDP 1,N6-ethenoadenosine 5'-triphosphate and particularly epsilon-ATP stimulate it. Both stimulation and protection occur at concentrations within the physiological range of ATP and carbamoyl phosphate. Inactivation of OTC is followed by extensive proteolysis. Since the inactivation is prevented by leupeptin, antipain and L-(tosylamido-2-phenyl)ethylchloromethyl ketone, the proteolytic susceptibility of OTC to lysosomes could be due to thiol endopeptidase(s). 1,N6-Ethenoadenosine 5'-triphosphate also markedly increases OTC susceptibility to trypsin and elastase. ATP analogs had no stimulatory effect on OTC inactivation by lysosomes; none of the inhibitors of ATPases tested inhibited the ATP effect. The ATP stimulation does not require Mg2+. These findings indicate a new role for ATP, GTP and related nucleotides in protein breakdown. The ATP, ADP, GTP, GDP stimulation, together with the carbamoyl protection of OTC, agree well with the molecular plasticity hypothesis model.
鸟氨酸转氨甲酰酶（OTC）被肝脏溶酶体灭活。氨甲酰磷酸可防止溶酶体对OTC的灭活，而ATP、ADP、GTP、GDP、1,N6-乙烯腺苷5'-三磷酸，尤其是ε-ATP可刺激其活性。刺激和保护作用均在ATP和氨甲酰磷酸的生理浓度范围内发生。OTC失活后会发生广泛的蛋白水解。由于亮抑酶肽、抗蛋白酶和L-（甲苯磺酰氨基-2-苯基）乙基氯甲基酮可阻止这种失活，因此OTC对溶酶体的蛋白水解敏感性可能归因于硫醇内肽酶。1,N6-乙烯腺苷5'-三磷酸也显著增加了OTC对胰蛋白酶和弹性蛋白酶的敏感性。ATP类似物对溶酶体介导的OTC失活没有刺激作用；所测试的ATP酶抑制剂均未抑制ATP的作用。ATP的刺激作用不需要Mg2+。这些发现表明ATP、GTP及相关核苷酸在蛋白质分解中具有新的作用。ATP、ADP、GTP、GDP的刺激作用，以及OTC的氨甲酰保护作用，与分子可塑性假说模型非常吻合。
