Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-(13) C]-l-lactate.
Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-(13) C]-l-lactate.
复制标题
使用超极化[1-（13）C]-l-乳酸评估肝丙酮酸羧化酶活性。
DOI：
10.1002/mrm.28489
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发表时间：
2021-03
影响因子：
3.3
通讯作者：
Park JM
中科院分区：
文献类型：
--
作者：
Chen J;Hackett EP;Kovacs Z;Malloy CR;Park JM
评价超极化[1- 13 C]-L-乳酸在体内检测进食和禁食条件下肝脏丙酮酸羧化酶（PC）活性的实用性。[1- 13 C]-标记的L-乳酸钠使用SPINlab偏振器偏振。在体外3 T MR扫描仪上测量极化水平和T1。制备两组健康大鼠（禁食与进食）用于体内研究。将每只大鼠麻醉并静脉注射60 mM超极化[1- 13 C]-L-乳酸盐，随后立即在3 T下动态采集肝脏的13 C MR光谱。还通过再次注射等体积的30 mM超极化[1- 13 C]-L-乳酸盐研究了13 C-产物的剂量依赖性。[1- 13 C]-L-乳酸盐的T1和液体极化水平分别估计为67.8秒和40.0%。除[1- 13 C]丙酮酸和[1- 13 C]丙氨酸外，[1 - 13 C] HCO_3 ~-和[1- 13 C]天冬氨酸在大鼠肝脏中由超极化的[1- 13 C]-L-乳酸产生。与禁食组相比，进食组中测得的HCO 3-较小，天冬氨酸较大。丙酮酸和丙氨酸的生产增加成比例的乳酸浓度，而HCO 3-和天冬氨酸的生产量是一致的30 mM和60 mM的乳酸注射液之间。这项研究表明，PC通量的独特生物标志物，[1 - 13 C]-L-乳酸盐中[1 - 13 C]天冬氨酸盐的出现对营养状态敏感，可以在3 T下进行体内监测。由于[13 C] HCO 3-主要由PDH通量产生，这些结果表明[1- 13 C]天冬氨酸和[13 C] HCO 3-的比率（天冬氨酸/HCO 3-）反映了饱和的PC/PDH酶活性。
To evaluate the utility of hyperpolarized [1-13C]-L-lactate to detect hepatic pyruvate carboxylase (PC) activity in vivo under fed and fasted conditions. [1-13C]-labeled sodium L-lactate was polarized using a SPINlab polarizer. Polarization level and the T1 were measured in vitro in a 3T MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously injected with 60-mM hyperpolarized [1-13C]-L-lactate, immediately followed by dynamic acquisition of 13C MR spectra from the liver at 3T. The dosage-dependence of the 13C-products was also investigated by performing another injection of an equal volume of 30-mM hyperpolarized [1-13C]-L-lactate. T1 and liquid polarization level of [1-13C]-L-lactate were estimated as 67.8 sec and 40.0%, respectively. Besides [1-13C]pyruvate and [1-13C]alanine, [13C]HCO3– and [1-13C]aspartate were produced from hyperpolarized [1-13C]-L-lactate in rat liver. Smaller HCO3– and larger aspartate were measured in the fed group compared to the fasted group. Pyruvate and alanine production were increased in proportion to the lactate concentration, whereas the amount of HCO3– and aspartate production was consistent between 30-mM and 60-mM lactate injections. This study demonstrates that a unique biomarker of PC flux, the appearance of [1-13C]aspartate from [1-13C]-L-lactate, is sensitive to nutritional state and may be monitored in vivo at 3T. Since [13C]HCO3– is largely produced by PDH flux, these results suggest that the ratio of [1-13C]aspartate and [13C]HCO3– (aspartate/HCO3–) reflects the saturable PC/PDH enzyme activities.
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影响因子：
13.5
作者：
Lee, Philip;Leong, Waifook;Radda, George K.
通讯作者：
Radda, George K.
影响因子：
2.8
作者：
Park, Jae Mo;Josan, Sonal;Jue, Thomas
通讯作者：
Jue, Thomas
影响因子：
15
作者：
Kennedy, Brett W. C.;Kettunen, Mikko I.;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.
DOI：
10.1111/j.1432-1033.1985.tb09250.x
发表时间：
1985-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
AGIUS, L;ALBERTI, KGMM
通讯作者：
ALBERTI, KGMM
影响因子：
5
作者：
Takado Y;Cheng T;Bastiaansen JAM;Yoshihara HAI;Lanz B;Mishkovsky M;Lengacher S;Comment A
通讯作者：
Comment A