Regulation of the hepatic glycine-cleavage system.
Regulation of the hepatic glycine-cleavage system.
复制标题
肝脏甘氨酸裂解系统的调节。
DOI：
10.1042/bst0141004
复制
发表时间：
1986
影响因子：
3.9
通讯作者：
Craig,F
中科院分区：
文献类型：
--
作者：
Olson,MS;Hampson,RK;Craig,F
采用与上述线粒体研究类似的实验原理对分离的灌注大鼠肝脏中的甘氨酸裂解进行了研究（Hampson 等人，19846）。在灌注液甘氨酸浓度接近10mM时获得[1-'4C]甘氨酸脱羧的最大速率(例如125nmol/min/g)。输注代谢底物（例如 3-羟基丁酸或辛酸）可分别抑制糖裂解率 33% 和 50%。代谢条件（例如 NH、CI、10 mM，加上丙酮酸或乳酸，5 mM）已被证明会导致尿素合成过程中线粒体内 NADPH 的快速消耗（Chamalaun & Tager，1970；Siess 等，1975），导致灌注大鼠肝脏的甘氨酸脱羧作用增加约三倍。丙酸盐几乎完全抑制甘氨酸脱羧和尿素合成的刺激速率。有人提出，丙酰辅酶A和/或甲基丙二酰辅酶A抑制尿素合成中选定的酶反应（Gruskay & Rosenberg，1979；Coude等，1979；Martin-Requero等，1983），并且在本研究中，丙酸很可能抑制尿素合成，从而阻止线粒体内PIADPH的消耗，从而抑制线粒体内PIADPH的消耗。甘氨酸裂解反应。一些实验室已经研究了半胱胺对甘氨酸裂解反应的抑制作用（例如参见Yud-koff 等，1981；Hayasaka & Tada，1983）。在本研究中，在尿原条件下观察到的甘氨酸脱羧的快速速率几乎完全被半胱胺的共输注所抑制。半胱胺抑制甘氨酸脱羧的精确机制目前正在研究中。总之，我们的实验方法表明，肝脏甘氨酸裂解系统主要受线粒体内 NAD (H) 和 NADP (H) 对的氧化还原状态的调节。这种类型的调节在正常代谢条件下是否具有生理上的重要性和/或是否会导致病理性高血糖状态，仍有待明确证明。
Glycine cleavage in the isolated perfused rat liver was investigated with a similar experimental rationale as in the mitochondrial studies discussed above (Hampson et al., 19846). Maximal rates of [l-'4C] glycine decarboxylation (eg 125 nmol/min per g) were attained at perfusate glycine concentrations approaching 10 mM. Infusion of metabolic substrates such as 3-hydroxybutyrate or octanoate inhibited the rate of glyciae cleavage by 33 and 50%, respectively. Metabolic conditions (eg NH, CI, 10 mM, plus pyruvate or lactate, 5 mM) which have been demonstrated to cause rapid consumption of intramitochondrial NADPH (Chamalaun & Tager, 1970; Siess et al., 1975) during urea synthesis caused an approximately three-fold increase in glycine decarboxylation by the perfused rat liver. The stimulated rate of glycine decarboxylation and the synthesis of urea were inhibited nearly completely by propionate. It has been suggested that propionyl-CoA and/or methylmalonyl-CoA inhibit selected enzymic reactions in urea synthesis (Gruskay & Rosenberg, 1979; Coude et al., 1979; Martin-Requero et al., 1983) and it is likely that, in the present study, propionate inhibited urea synthesis, thus preventing the consumption of intramitochondrial PIADPH which in turn inhibited the glycine-cleavage reaction. Several laboratories have investigated the inhibitory effects of cysteamine on the glycine-cleavage reaction (eg see Y ud-koff et al., 1981; Hayasaka & Tada, 1983). In the present study the rapid rates of glycine decarboxylation observed under ureogenic conditions were inhibited nearly completely by co-infusion of cysteamine. The precise mechanism by which cysteamine inhibits glycine decarboxylation is presently under investigation. In summary, our experimental approach has demonstrated that the hepatic glycine-cleavage system is regulated primarily by the oxidation-reduction state of the intramitochondrial NAD (H) and NADP (H) couples. Whether this type of regulation is physiologically important under normal metabolic conditions and/or contributes to pathological hyperglycinaemic states, remains to be demonstrated definitively.