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大鼠脑不同亚细胞组分线粒体中γ-氨基丁酸转氨酶受底物类似物的抑制作用。

The inhibition by substrate analogues of gamma-aminobutyrate aminotransferase from mitochondria of different subcellular fractions of rat brain.

作者信息

Tunnicliff G, Ngo T T, Rojo-Ortega J M, Barbeau A

出版信息

Can J Biochem. 1977 Apr;55(4):479-84. doi: 10.1139/o77-067.

DOI:10.1139/o77-067
PMID:870153
Abstract

Cytoplasmic-mitochondria-enriched and synaptosome-enriched subcellular fractions were prepared from rat brain to study certain kinetic properties of gamma-aminobutyrate: alpha-oxoglutarate aminotransferase (GABA-T) (EC 2.6.1.19) from each of the sources. From this study two differences emerged. Firstly, the cytoplasmic enzyme exhibited an eightfold greater affinity for gamma-aminobutyric acid (GABA) than did the synaptosomal GABA-T; the Km being 6.5 mM and 53 mM, respectively. Secondly, synaptosomal GABA-T is comparatively more susceptible to inhibition by the substrate analogues 2,4-diaminobutyric acid (DABA) and aminooxyacetic acid (AOAA) than is the enzyme from the cytoplasmic mitochondrial fraction. In each case the inhibition was of a competitive nature with respect to GABA. The Ki for the DABA was 13 mM for the cytoplasmic-derived enzyme and 8mM for the synaptosomal enzyme. With AOAA the Ki was 0.1 muM and 0.06 muM for the synaptosomal and cytoplasmic mitochondrial enzyme, respectively. These results provide further evidence that GABA-T from cytoplasmic mitochondria is different in several respects from the enzyme found in synaptosomes.

摘要

从大鼠脑中制备富含细胞质线粒体和富含突触体的亚细胞组分,以研究来自每种来源的γ-氨基丁酸:α-酮戊二酸转氨酶(GABA-T)(EC 2.6.1.19)的某些动力学特性。从这项研究中出现了两个差异。首先,细胞质酶对γ-氨基丁酸(GABA)的亲和力比突触体GABA-T高八倍;Km分别为6.5 mM和53 mM。其次,与来自细胞质线粒体组分的酶相比,突触体GABA-T相对更容易受到底物类似物2,4-二氨基丁酸(DABA)和氨基氧乙酸(AOAA)的抑制。在每种情况下,抑制作用相对于GABA都是竞争性的。细胞质来源的酶对DABA的Ki为13 mM,突触体酶为8 mM。对于AOAA,突触体和细胞质线粒体酶的Ki分别为0.1 μM和0.06 μM。这些结果进一步证明,细胞质线粒体中的GABA-T在几个方面与突触体中的酶不同。

相似文献

1
The inhibition by substrate analogues of gamma-aminobutyrate aminotransferase from mitochondria of different subcellular fractions of rat brain.大鼠脑不同亚细胞组分线粒体中γ-氨基丁酸转氨酶受底物类似物的抑制作用。
Can J Biochem. 1977 Apr;55(4):479-84. doi: 10.1139/o77-067.
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N-(5'-Phosphopyridoxyl)-4-aminobutyric acid: a stabel bisubstrate adduct inhibitor of rat brain 4-aminobutyric acid aminotransferase.N-(5'-磷酸吡哆醛基)-4-氨基丁酸:大鼠脑4-氨基丁酸转氨酶的一种稳定双底物加合物抑制剂。
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omega-Fluoromethyl analogues of omega-amino acids as irreversible inhibitors of 4-aminobutyrate:2-oxoglutarate aminotransferase.ω-氨基酸的ω-氟甲基类似物作为4-氨基丁酸:2-氧代戊二酸转氨酶的不可逆抑制剂
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Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria.“突触体”和游离大鼠脑线粒体中4-氨基丁酸代谢调控的研究
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Differences in biochemical properties of gamma-aminobutyric acid aminotransferase from synaptosome-enriched and cytoplasmic mitochondria-enriched subcellular fractions of mouse brain.来自小鼠脑富含突触体和富含细胞质线粒体的亚细胞组分的γ-氨基丁酸转氨酶的生化特性差异。
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Comparative study of the inhibition of GABA aminotransferase by different anticonvulsant drugs.不同抗惊厥药物对γ-氨基丁酸转氨酶抑制作用的比较研究。
Arch Int Pharmacodyn Ther. 1980 Jan;243(1):48-55.

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