“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

Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria.

作者信息

Walsh J M, Clark J B

出版信息

Biochem J. 1976 Nov 15;160(2):147-57. doi: 10.1042/bj1600147.

DOI:10.1042/bj1600147

PMID:188415

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1164216/

Abstract

The specific activities of 4-aminobutyrate aminotransferase (EC 2.6.1.19) and succinate semialdehyde dehydrogenase (EC 1.2.1.16) were significantly higher in brain mitochondria of non-synaptic origin (fraction M) than those derived from the lysis of synaptosomes (fraction SM2). 2. The metabolisms of 4-aminobutyrate in both 'free' (non-synaptic, fraction M) and 'synaptic' (fraction SM2) rat brain mitochondria was studied under various conditions. 3. It is proposed that 4-aminobutyrate enters both types of brain mitochondria by a non-carrier-mediated process. 4. The rate of 4-aminobutyrate metabolism was in all cases higher in the 'free' (fraction M) brain mitochondria than in the synaptic (fraction SM2) mitochondria, paralleling the differences in the specific activities of the 4-aminobutyrate-shunt enzymes. 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase. 6. The redox state of the intramitochondrial NAD pool is also important in the control of 4-aminobutyrate metabolism; NADH exhibits competitive inhibition of 4-aminobutyrate metabolism by both mitochondrial populations with an apparent Ki of 102 muM. 7. Increased potassium concentrations stimulate 4-aminobutyrate metabolsim in the synaptic mitochondria but not in 'free' brain mitochondria. This is discussed with respect to the putative transmitter role of 4-aminobutyrate.

摘要

非突触来源的脑线粒体（组分M）中4-氨基丁酸转氨酶（EC 2.6.1.19）和琥珀酸半醛脱氢酶（EC 1.2.1.16）的比活性显著高于源自突触体裂解的线粒体（组分SM2）。2. 在各种条件下研究了大鼠脑“游离”（非突触，组分M）和“突触”（组分SM2）线粒体中4-氨基丁酸的代谢。3. 提出4-氨基丁酸通过非载体介导的过程进入两种类型的脑线粒体。4. 在所有情况下，“游离”（组分M）脑线粒体中4-氨基丁酸的代谢速率均高于突触（组分SM2）线粒体，这与4-氨基丁酸分流酶的比活性差异平行。5. 2-氧代戊二酸的线粒体内浓度似乎是4-氨基丁酸代谢速率的一个重要控制参数，因为尽管需要2-氧代戊二酸，但高浓度（2.5 mM）的线粒体外2-氧代戊二酸会抑制通过谷氨酸-草酰乙酸转氨酶形成天冬氨酸。6. 线粒体内NAD池的氧化还原状态在4-氨基丁酸代谢的控制中也很重要；NADH对两种线粒体群体的4-氨基丁酸代谢均表现出竞争性抑制，表观Ki为102 μM。7. 钾浓度升高刺激突触线粒体中4-氨基丁酸的代谢，但不刺激“游离”脑线粒体中的代谢。这是从4-氨基丁酸假定的递质作用方面进行讨论的。