Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices
Effects of Ammonium Chloride, Salicylate, and Carnitine on Palmitic Acid Oxidation in Rat Liver Slices
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氯化铵、水杨酸盐和肉碱对大鼠肝切片中棕榈酸氧化的影响
DOI：
10.1203/00006450-198902000-00003
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发表时间：
1989
影响因子：
3.6
通讯作者：
P. Miller
中科院分区：
文献类型：
--
作者：
V. Maddaiah;P. Miller
摘要：为探讨高脂血症与高氨血症和阿司匹林摄入之间的关系，本实验研究了NH4 +、水杨酸盐和肉碱对[l-14C]棕榈酸氧化为酸溶产物（ASP）和氧化为CO2的影响，结果表明：dl -肉碱（5 mM）使总氧化（ASP + CO2）大于氧化为CO2。KCN （1.5 mM）抑制了90%以上的氧化。NH4Cl对氧化的抑制作用在40mm左右达到最大，但对CO2的抑制作用（63%）大于对总氧化的抑制作用（30%）。肉碱不影响NH4 +抑制，这与分离线粒体的结果一致。水杨酸的作用取决于水杨酸的浓度以及肉碱的存在。在不添加肉碱的情况下，3 mM水杨酸对总氧化的抑制率为90%，而对CO2的氧化抑制率为50%。在饱和棕榈酸浓度下计算的总氧化速度增加0.75 mM水杨酸盐，但氧化成CO2的速度增加更大。当水杨酸浓度为3 mM时，饱和棕榈酸浓度下的氧化速率降低，但氧化为CO2的速率降低幅度小于总氧化速率。肉碱部分解除了对总氧化的抑制，进一步增加了CO2的形成。20 mM NH4Cl和0.75 mM水杨酸对总氧化的抑制作用大于单个效应的加和作用，肉碱部分缓解了这种抑制作用。综上所述，NH4 +对CO2氧化的抑制作用强于对ASP氧化的抑制作用，而水杨酸盐对ASP氧化的抑制作用较强，但通过线粒体氧化磷酸化解偶联而增加了对CO2氧化的抑制作用。因此，高氨血症和阿司匹林的摄入可以抑制脂肪酸氧化和线粒体代谢，从而导致一些儿童疾病（如雷氏综合征）的病理生理。肉碱疗法可能会带来一些好处。
ABSTRACT: To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4 +, salicylate, and carnitine on the oxidation of [l-14C]palmitic acid to acid-soluble products (ASP) and to CO2 were investigated in rat liver slices, DL-carnitine (5 mM) increased total oxidation (ASP + CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90% of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2 (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4 + inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to CO2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2 was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4 + exerted a stronger inhibition of oxidation to CO2 than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2 by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits.
水杨酸盐引起的松耦合：质子动力测量。
影响因子：
5.8
作者：
Haas,R;ParkerJr,WD;Stumpf,D;Eguren,LA
通讯作者：
Eguren,LA
阿司匹林是雷氏综合症的危险因素。
DOI：
--
发表时间：
1982
期刊：
JAMA : the journal of the American Medical Association
影响因子：
--
作者：
Waldman,RJ;Hall,WN;McGee,H;VanAmburg,G
通讯作者：
VanAmburg,G
DOI：
--
发表时间：
1982
期刊：
Federation proceedings
影响因子：
--
作者：
Bieber,LL;Emaus,R;Valkner,K;Farrell,S
通讯作者：
Farrell,S