由肾上腺切除和链脲佐菌素诱导糖尿病大鼠制备的肝细胞对L-色氨酸的代谢

The metabolism of L-tryptophan by liver cells prepared from adrenalectomized and streptozotocin-diabetic rats.

作者信息

Smith S A, Pogson C I

出版信息

Biochem J. 1981 Dec 15;200(3):605-9. doi: 10.1042/bj2000605.

DOI:10.1042/bj2000605

PMID:7342971

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1163583/

Abstract

The metabolism of L-tryptophan by liver cells prepared from fed normal, adrenalectomized and streptozotocin-diabetic rats was studied. 2. At physiological concentrations (0.1 mM), the rate of oxidation of tryptophan by tryptophan 2,3-dioxygenase was 3-fold greater in liver cells from diabetic rats than in those from fed rats. In liver cells from diabetic rats, oxidation of tryptophan to CO2 and metabolites of the glutarate pathway was increased 7-fold. Quinolinate synthesis was decreased by 50%. These findings are consistent with an increase in picolinate carboxylase activity. 3. Rates of metabolism of 0.1 mM-tryptophan by hepatocytes from fed and adrenalectomized rats were similar. 4. In all three types of cell preparation, fluxes through tryptophan 2,3-dioxygenase with 2.5 mM-tryptophan were 7-fold greater than those obtained with 0.1 mM-tryptophan. Tryptophan 2,3-dioxygenase and kynureninase fluxes in hepatocytes from fed and adrenalectomized rats were comparable, whereas those in liver cells from diabetic rats were increased 2.5-fold and 3.3-fold respectively. Picolinate carboxylase activities of liver cells from diabetic rats were 15-fold greater than those of cells from fed rats, but rates of quinolinate synthesis were unchanged. 5. It is concluded that: (i) adrenal corticosteroids are not required for the maintenance of basal activities of the kynurenine pathway, whereas (ii) chronic insulin deficiency produces changes in both the rate of oxidation and metabolic fate of tryptophan carbon.

摘要

研究了从正常进食、肾上腺切除和链脲佐菌素诱导糖尿病大鼠制备的肝细胞中L-色氨酸的代谢情况。2. 在生理浓度（0.1 mM）下，糖尿病大鼠肝细胞中色氨酸2,3-双加氧酶将色氨酸氧化的速率比正常进食大鼠肝细胞中的速率高3倍。在糖尿病大鼠肝细胞中，色氨酸氧化为二氧化碳和戊二酸途径代谢产物的量增加了7倍。喹啉酸合成减少了50%。这些发现与吡啶甲酸羧化酶活性增加一致。3. 正常进食和肾上腺切除大鼠肝细胞对0.1 mM色氨酸的代谢速率相似。4. 在所有三种细胞制备类型中，2.5 mM色氨酸通过色氨酸2,3-双加氧酶的通量比0.1 mM色氨酸的通量高7倍。正常进食和肾上腺切除大鼠肝细胞中色氨酸2,3-双加氧酶和犬尿氨酸酶的通量相当，而糖尿病大鼠肝细胞中的通量分别增加了2.5倍和3.3倍。糖尿病大鼠肝细胞的吡啶甲酸羧化酶活性比正常进食大鼠肝细胞的高15倍，但喹啉酸合成速率不变。5. 得出以下结论：（i）维持犬尿氨酸途径的基础活性不需要肾上腺皮质类固醇，而（ii）慢性胰岛素缺乏会导致色氨酸碳的氧化速率和代谢命运发生变化。