Clark B R, Murai J T, Pomeranz A, Mills P A, Halpern R M
Cancer Res. 1975 Jul;35(7):1727-33.
Levels of nicotinamide and N-1-methylnicotinamide in serum, liver, and kidney as well as renal clearances and 24-hr urine levels of N-1-methylnicotinamide were compared in normal rats and rats bearing Walker 256 tumors. There was no significant difference between normal and tumor-bearing rats with regard to nicotinamide levels. With regard to N-1-methylnicotinamide, tumor-bearing rats had significantly lower serum and liver levels and significantly higher 24-hr urine levels and renal clearances. Walker 256 tumor tissue and liver and kidney from a normal and a tumor-bearing rat were separately examined for S-adenosylmethionine:nicotinamide methyltransferase activity. The specific activity in tumor tissue extract was greater than that in each liver extract, which, in turn, was much greater than the specific activity in each tissue (liver and kidney) from the tumor-bearing rat was equal to the specific activity in the corresponding tissue of the normal rat. S-adenosylmethionine:nicotinamide methyltransferase was obtained with 18-fold purification from a tissue extract of Walker 256 tumor. The enzyme activity required activation by thiols, and maximal activity was observed at pH 8.6. The Km's for the substrates, S-adenosylmethionine and nicotinamide, were 7.0 x 10--3 mM and 0.50 mM respectively. The Ki's for the products, S-adenosylhomocysteine and N-1-methylnicotinamide, were respectively, 25 x 10--3 mM and greater than 5 mM.
比较了正常大鼠和荷Walker 256肿瘤大鼠血清、肝脏和肾脏中烟酰胺和N-1-甲基烟酰胺的水平，以及N-1-甲基烟酰胺的肾清除率和24小时尿水平。在烟酰胺水平方面，正常大鼠和荷瘤大鼠之间没有显著差异。关于N-1-甲基烟酰胺，荷瘤大鼠的血清和肝脏水平显著降低，24小时尿水平和肾清除率显著升高。分别检测了正常大鼠和荷瘤大鼠的Walker 256肿瘤组织以及肝脏和肾脏中的S-腺苷甲硫氨酸：烟酰胺甲基转移酶活性。肿瘤组织提取物中的比活性大于每个肝脏提取物中的比活性，而每个肝脏提取物中的比活性又远大于荷瘤大鼠每个组织（肝脏和肾脏）中的比活性，荷瘤大鼠相应组织中的比活性与正常大鼠的相等。从Walker 256肿瘤的组织提取物中以18倍纯化获得了S-腺苷甲硫氨酸：烟酰胺甲基转移酶。该酶活性需要硫醇激活，在pH 8.6时观察到最大活性。底物S-腺苷甲硫氨酸和烟酰胺的Km值分别为7.0×10⁻³ mM和0.50 mM。产物S-腺苷同型半胱氨酸和N-1-甲基烟酰胺的Ki值分别为25×10⁻³ mM和大于5 mM。
