Do branched chain keto amino acids regulate their own metabolism?
Do branched chain keto amino acids regulate their own metabolism?
复制标题
支链酮氨基酸调节自身代谢吗？
作者：
P. Schauder
本文研究了支链α-酮酸对喂饲、饥饿和低蛋白饮食大鼠肝细胞中支链α-酮酸脱氢酶复合体的通透性和活性状态的影响。极低浓度的α-酮基异戊酸可显著刺激低蛋白饮食大鼠肝细胞的α-酮基异戊酸脱羧化反应(20 M时激活50%)。α-酮-β-甲基戊酸酯也有效，但不如α-酮基异戊酸酯有效。α-酮基异戊酸酯不能刺激喂养或饥饿大鼠肝细胞的α-酮基异戊酸脱羧基。α-酮-β-甲基戊酸酯和α-酮基异戊酸酯对低蛋白喂养大鼠肝细胞α-酮基异戊酸脱羧化的刺激作用较小。通过支链α-酮酸脱氢酶刺激通量的效价顺序为：α-酮基异戊酸酯>；α-酮-β-甲基戊酸酯>；α-酮西戊酸，即这些化合物与支链α-酮酸脱氢酶激酶抑制剂的效价顺序相同。已知的氟抑制支链α-酮酸脱氢酶磷酸酶，通过支链α-酮酸脱氢酶在很大程度上阻止了α-酮基异己酸和α-氯异己酸对熔剂的激活。对低蛋白饮食大鼠肝细胞无细胞提取物中支链α-酮酸复合体的分析证实，α-酮酸影响了该复合体的活性状态。支链α-酮酸未能激活喂食和饥饿大鼠制备的肝细胞中的通量，因为基本上所有的复合体都已经处于去磷酸化的活性状态。这些结果表明，支链α-酮酸抑制支链α-酮酸脱氢酶的活性对调节肝脏支链α-酮酸脱氢酶的活性状态具有重要意义。
The effects of branched‐chain α‐ketoacids on flux through and activity state of the branched‐chain α‐ketoacid dehydrogenase complex were studied in hepatocytes prepared from chow‐fed, starved, and low‐protein‐diet‐fed rats. Very low concentrations of α‐ketoisocaproate caused a dramatic stimulation (50% activation at 20 μM) of α‐ketoisovalerate decarboxylation in hepatocytes from low‐protein‐fed rats. α‐Keto‐β‐methylvalerate was also effective, but less so than α‐ketoisocaproate. α‐Ketoisocaproate did not stimulate α‐ketoisovalerate decarboxylation by hepatocytes from chow‐fed or starved rats. To a smaller degree, α‐keto‐β‐methylvalerate and α‐ketoisovalerate stimulated α‐ketoisocaproate decarboxylation by hepatocytes from low‐protein‐fed rats. The implied order of potency of stimulation of flux through branched‐chain α‐ketoacid dehydrogenase was α‐ketoisocaproate > α‐keto‐β‐methylvalerate > α‐ketosiovalerate, i.e., the same order of potency of these compounds as branched‐chain α‐ketoacid dehydrogenase kinase inhibitors. Fluoride, known to inhibit branched‐chain α‐ketoacid dehydrogenase phosphatase, largely prevented α‐ketoisocaproate and α‐chloroisocaproate activation of flux through the branched‐chain α‐ketoacid dehydrogenase. Assay of the branched‐chain α‐ketoacid complex in cell‐free extracts of hepatocytes isolated from low‐protein‐diet‐fed rats confirmed that α‐ketoacids affected the activity state of the complex. Branched‐chain α‐ketoacids failed to activate flux in hepatocytes prepared from chow‐fed and starved rats because essentially all of the complex was already in the dephosphorylated, active state. These findings indicate that inhibition of branched‐chain α‐ketoacid dehydrogenase kinase activity by branched‐chain α‐ketoacids is important for regulation of the activity state of hepatic branched‐chain α‐ketoacid dehydrogenase.
膳食蛋白质摄入量对大鼠支链酮酸脱氢酶活性的影响。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Miller,RH;Eisenstein,RS;Harper,AE
通讯作者：
Harper,AE
脾切除术对接受多于一次肾移植的患者生存的不利影响。
影响因子：
6.2
作者：
Shofer,FS;London,WT;Lyons,P;Simonian,SJ;Burke,JF;Jarrell,BE;Grossman,RA;Barker,CF
通讯作者：
Barker,CF
远端脾肾分流术后的门静脉循环。
影响因子：
25.7
作者：
Henderson,JM;Gong-Liang,J;Galloway,J;MillikanJr,WJ;Sones,PJ;Warren,WD
通讯作者：
Warren,WD