大鼠肝脏中烟酰胺核苷酸稳态浓度的调控

Control of the steady-state concentrations of the nicotinamide nucleotides in rat liver.

作者信息

Clark J B, Pinder S

出版信息

Biochem J. 1969 Sep;114(2):321-30. doi: 10.1042/bj1140321.

DOI:10.1042/bj1140321

PMID:4390211

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1184858/

Abstract

The effects of injecting nicotinamide, 5-methylnicotinamide, ethionine, nicotinamide+5-methylnicotinamide and nicotinamide+ethionine on concentrations in rat liver of NAD, NADP and ATP were investigated up to 5hr. after injection. 2. Nicotinamide induced three- to four-fold increases in hepatic NAD concentration even in the presence of 5-methylnicotinamide or ethionine, whereas 5-methylnicotinamide or ethionine alone did not cause marked changes in hepatic NAD concentration. 3. Nicotinamide alone also induced a twofold increase in hepatic NADP concentration. However, in the presence of 5-methylnicotinamide+nicotinamide, the NADP concentration decreased by 25% after 5hr., and in the presence of nicotinamide+ethionine by 30% in the same time. In the presence of 5-methylnicotinamide or ethionine alone hepatic NADP concentrations fell by 50% after 5hr. 4. 5-Methylnicotinamide inhibited the microsomal NAD(+) glycohydrolase (EC 3.2.2.6) by 60% at a concentration of 1mm and the NADP(+) glycohydrolase by 40% at the same concentration. 5. The rat liver NAD(+) kinase (EC 2.7.1.23) was found to have V(max.) 4.83mumoles/g. wet wt./hr. and K(m) (NAD(+)) 5.8mm. This enzyme was also inhibited by 5-methylnicotinamide in a ;mixed' fashion. 6. The results are discussed with respect to the control of NAD synthesis. It is suggested that in vivo the NAD(P)(+) glycohydrolases are effectively inactive and that the increased NAD concentrations induced by nicotinamide are due to increased substrate concentration available to both the nicotinamide and nicotinic acid pathways of NAD formation.

摘要

研究了注射烟酰胺、5-甲基烟酰胺、乙硫氨酸、烟酰胺 + 5-甲基烟酰胺以及烟酰胺 + 乙硫氨酸对大鼠肝脏中NAD、NADP和ATP浓度的影响，观察时间长达注射后5小时。2. 即使存在5-甲基烟酰胺或乙硫氨酸，烟酰胺仍能使肝脏NAD浓度增加三到四倍，而单独的5-甲基烟酰胺或乙硫氨酸不会引起肝脏NAD浓度的显著变化。3. 单独的烟酰胺也能使肝脏NADP浓度增加两倍。然而，在存在5-甲基烟酰胺 + 烟酰胺的情况下，5小时后NADP浓度下降了25%，在存在烟酰胺 + 乙硫氨酸的情况下，同一时间下降了30%。单独存在5-甲基烟酰胺或乙硫氨酸时，5小时后肝脏NADP浓度下降了50%。4. 5-甲基烟酰胺在浓度为1mM时对微粒体NAD(+)糖水解酶（EC 3.2.2.6）的抑制率为60%，对NADP(+)糖水解酶的抑制率在相同浓度下为40%。5. 发现大鼠肝脏NAD(+)激酶（EC 2.7.1.23）的V(max.)为4.83微摩尔/克湿重/小时，K(m)（NAD(+)）为5.8mM。该酶也受到5-甲基烟酰胺以“混合型”方式的抑制。6. 针对NAD合成的控制对结果进行了讨论。有人提出，在体内NAD(P)(+)糖水解酶实际上是无活性的，烟酰胺诱导的NAD浓度增加是由于可用于NAD形成的烟酰胺和烟酸途径的底物浓度增加所致。