离体大鼠肝细胞的色氨酸代谢——亮氨酸及其代谢产物的影响

Tryptophan metabolism by the isolated rat liver cells--effects of leucine and its metabolites.

Kiyohara Y, Shirasawa K, Shin M, Sano K, Umezawa C

School of Pharmacy, Kobe-Gakuin University, Japan.

Int J Vitam Nutr Res. 1989;59(1):85-92.

Abstract

The effects of leucine and its metabolites, such as alpha-ketoisocaproate and ketone bodies, on the metabolic fluxes of tryptophan were investigated in isolated rat liver cells using [benzene ring-U-14C]- or [methylene-14C]-tryptophan. 2. Tryptophan metabolized through the kynureninase flux decreased while that metabolized to acetyl CoA remained unchanged in the presence of leucine or its metabolites. Accordingly an amount of tryptophan metabolized through the quinolinate-NAD pathway, which was estimated by subtracting an amount of tryptophan metabolized via the acetyl CoA flux from that via the kynureninase flux, was decreased in the presence of leucine or its metabolites. 3. Less quinolinate accumulated during incubation with metabolites of leucine, however, the amount was still sufficient to saturate quinolinate phosphoribosyltransferase (EC 2.4.2.19). 4. Leucine and its metabolites added in vitro at 1 mM level did not inhibit quinolinate phosphoribosyltransferase activity in rat liver homogenate. 5. The results indicate that a decrease in NAD biosynthesis from tryptophan caused by metabolites of leucine in the isolated rat liver cells was neither due to insufficient supply of quinolinate nor to direct inhibitory effect on quinolinate phosphoribosyltransferase.

摘要

使用[苯环-U-14C]-或[亚甲基-14C]-色氨酸，在分离的大鼠肝细胞中研究了亮氨酸及其代谢产物，如α-酮异己酸和酮体，对色氨酸代谢通量的影响。2. 在亮氨酸或其代谢产物存在的情况下，通过犬尿氨酸酶通量代谢的色氨酸减少，而代谢为乙酰辅酶A的色氨酸保持不变。因此，通过喹啉酸-NAD途径代谢的色氨酸量（通过从犬尿氨酸酶通量代谢的色氨酸量中减去通过乙酰辅酶A通量代谢的色氨酸量来估算）在亮氨酸或其代谢产物存在时减少。3. 在与亮氨酸代谢产物孵育期间积累的喹啉酸较少，然而，该量仍足以使喹啉酸磷酸核糖基转移酶（EC 2.4.2.19）饱和。4. 在体外以1 mM的水平添加亮氨酸及其代谢产物不会抑制大鼠肝脏匀浆中喹啉酸磷酸核糖基转移酶的活性。5. 结果表明，分离的大鼠肝细胞中亮氨酸代谢产物导致的色氨酸生成NAD减少，既不是由于喹啉酸供应不足，也不是由于对喹啉酸磷酸核糖基转移酶的直接抑制作用。