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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues.
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Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues.

机译：氨基酸及其合成类似物对大鼠脑线粒体中谷氨酰胺摄取和磷酸激活的谷氨酰胺酶活性的调节。

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摘要

Uptake of L-[14C]Gln and phosphate-activated glutaminase (PAG) activity were measured in nonsynaptic mitochondria isolated from rat cerebral hemispheres, in the presence of protein and nonprotein amino acids and their synthetic structural analogues and derivatives. The uptake was inhibited by > 50% in the presence of a 10-fold excess of His, homocysteine (Hcy), Trp, Leu, Tyr, Ile, Thr, Ala, Phe, Met, Ser, by > 20% in the presence of a 10-fold excess of Val, Arg, Glu, and was not affected by a 10-fold excess of Orn, alpha-ketoglutarate, Tau and Pro. Uptake of L-[14C] Leu differed from Gln uptake by its resistance to Arg, Glu, and a relatively high sensitivity to the reference inhibitor of the plasma membrane transport of large neutral amino acids (L-system)--BCH (2-aminobicyclo[2.2.1]heptane-2-carboxylic acid), and a number of natural L-system substrates. A newly synthesized alanine analogue, 2'-cyano-(biphenyl) alanine, referred to as MRC01, was the only compound tested that inhibited Gln uptake more strongly than Leu uptake. The strongest Gln uptake inhibitors: MRC01, His, Hcy and Leu, inhibited PAG activity by > 50% when added at the inhibitor/Gln concentration ratio of 1:2. PAG activity was not affected by Tau, Lys or Pro, compounds which did affect Gln uptake. The results suggest that a number of natural amino acids function as common endogenous modulators of cerebral mitochondrial Gln uptake and its degradation. MRC01, because of its inhibitory potency towards both mitochondrial Gln uptake and PAG activity, may become a convenient tool in studying the role of Gln transport in its mitochondrial metabolism in intact CNS cell and tissues.
机译：在存在蛋白质和非蛋白质氨基酸及其合成结构类似物和衍生物的情况下，在从大鼠脑半球分离的非突触线粒体中测量了L- [14C] Gln的摄取和磷酸激活的谷氨酰胺酶（PAG）的活性。在存在10倍过量的His，高半胱氨酸（Hcy），Trp，Leu，Tyr，Ile，Thr，Ala，Phe，Met，Ser的情况下，摄取> 50％被抑制> 20％ Val，Arg，Glu过量10倍，并且不受Orn，α-酮戊二酸酯，Tau和Pro过量10倍的影响。 L- [14C] Leu的吸收与Gln的吸收不同，其对Arg，Glu的抗性以及对大中性氨基酸（L系统）-BCH的质膜转运参考抑制剂的较高敏感性（2-氨基双环[2.2.1]庚烷-2-羧酸）和许多天然L系统底物。一种新合成的丙氨酸类似物2'-氰基-（联苯）丙氨酸，称为MRC01，是唯一测试的抑制Gln吸收比Leu吸收更强烈的化合物。最强的Gln吸收抑制剂：MRC01，His，Hcy和Leu，当抑制剂/ Gln的浓度比为1：2时，PAG活性抑制> 50％。 PAG活性不受确实影响Gln摄取的Tau，Lys或Pro化合物的影响。结果表明，许多天然氨基酸是大脑线粒体Gln摄取及其降解的常见内源性调节剂。由于MRC01对线粒体Gln摄取和PAG活性均具有抑制作用，因此它可能成为研究Gln转运在完整CNS细胞和组织中线粒体代谢中的作用的便捷工具。

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