肾上腺素和胰高血糖素对灌注大鼠心脏中支链2-氧代酸脱氢酶复合体的急性调节作用

Acute regulation of the branched-chain 2-oxo acid dehydrogenase complex by adrenaline and glucagon in the perfused rat heart.

作者信息

Hildebrandt E F, Buxton D B, Olson M S

机构信息

Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.

出版信息

Biochem J. 1988 Mar 15;250(3):835-41. doi: 10.1042/bj2500835.

DOI:10.1042/bj2500835

PMID:3134009

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1148931/

Abstract

Rates of transamination and decarboxylation of [1-14C]leucine at a physiological concentration (0.1 mM) were measured in the perfused rat heart. In hearts from fasted rats, metabolic flux through the branched-chain 2-oxo acid dehydrogenase reaction was low initially, but increased gradually during the perfusion period. The increase in 14CO2 production was accompanied by an increase in the amount of active branched-chain 2-oxo acid dehydrogenase complex present in the tissue. In hearts from rats fed ad libitum, extractable branched-chain dehydrogenase activity was low initially, but increased rapidly during perfusion, and high rates of decarboxylation were attained within the first 10 min. Infusion of glucagon, adrenaline, isoprenaline, or adrenaline in the presence of phentolamine all produced rapid, transient, inhibition (40-50%) of the formation of 4-methyl-2-oxo[1-14C]pentanoate and 14CO2 within 1-2 min, but the specific radioactivity of 4-methyl-2-oxo[14C]pentanoate released into the perfusate remained constant. Glucagon and adrenaline infusion also resulted in transient decreases (16-24%) in the amount of active branched-chain 2-oxo acid dehydrogenase. In hearts from fasted animals, infusion for 10 min of adrenaline, phenylephrine, or adrenaline in the presence of propranolol, but not infusion of glucagon or isoprenaline, stimulated the rate of 14CO2 production 3-fold, and increased 2-fold the extractable branched-chain 2-oxo acid dehydrogenase activity. These results demonstrate that stimulation of glucagon or beta-adrenergic receptors in the perfused rat heart causes a transient inhibition of branched-chain amino acid metabolism, whereas alpha-adrenergic stimulation causes a slower, more sustained, enhancement of branched-chain amino acid metabolism. Both effects reflect interconversion of the branched-chain 2-oxo acid dehydrogenase complex between active and inactive forms. Also, these studies suggest that the concentration of branched-chain 2-oxo acid available for decarboxylation can be regulated by adrenaline and glucagon.

摘要

在灌注的大鼠心脏中，测定了生理浓度（0.1 mM）下[1-¹⁴C]亮氨酸的转氨作用和脱羧作用速率。在禁食大鼠的心脏中，通过支链2-氧代酸脱氢酶反应的代谢通量最初较低，但在灌注期间逐渐增加。¹⁴CO₂产生的增加伴随着组织中活性支链2-氧代酸脱氢酶复合物量的增加。在自由进食大鼠的心脏中，可提取的支链脱氢酶活性最初较低，但在灌注期间迅速增加，并且在最初10分钟内达到较高的脱羧速率。注入胰高血糖素、肾上腺素、异丙肾上腺素或在酚妥拉明存在下注入肾上腺素，均在1-2分钟内迅速、短暂地抑制（40-50%）4-甲基-2-氧代[1-¹⁴C]戊酸酯和¹⁴CO₂的形成，但释放到灌注液中的4-甲基-2-氧代[¹⁴C]戊酸酯的比放射性保持恒定。注入胰高血糖素和肾上腺素还导致活性支链2-氧代酸脱氢酶的量短暂减少（16-24%）。在禁食动物的心脏中，注入肾上腺素、去氧肾上腺素10分钟或在普萘洛尔存在下注入肾上腺素，但不注入胰高血糖素或异丙肾上腺素，可使¹⁴CO₂产生速率增加3倍，并使可提取的支链2-氧代酸脱氢酶活性增加2倍。这些结果表明，灌注的大鼠心脏中胰高血糖素或β-肾上腺素能受体的刺激会导致支链氨基酸代谢的短暂抑制，而α-肾上腺素能刺激会导致支链氨基酸代谢的较慢、更持久的增强。这两种作用都反映了支链2-氧代酸脱氢酶复合物在活性和非活性形式之间的相互转化。此外，这些研究表明，可用于脱羧的支链2-氧代酸的浓度可由肾上腺素和胰高血糖素调节。