Tanaka K, Ichihara A
Biochim Biophys Acta. 1975 Aug 13;399(2):302-12.
Ketone body formation from tyrosine was studied in rat liver in vitro with special references to the activities of tyrosine aminotransferse (EC 2.6.1.5) and p-hydroxyphenylpyruvate hydroxylase (EC 1.14.2.2). Liver was obtained from rats which had been given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase. The enzyme activities of the preparations were plotted against the amounts of ketone body formed from tyrosine. It was found that over a low range of tyrosine aminotransferase activities, activity was proportional to the amount of ketone body formed. However, above this range, ketone body formation ceased to increase and p-hydroxyphenylpyruvate started to accumulate. This inhibition of ketone body formation and accumulation of the p-hydroxyphenylpyruvate could be prevented by addition of ascorbate. These results suggest that the primary factor regulating metabolism of tyrosine in vitro is tyrosine aminotransferase and when the activity of this is high so that it is no longer rate limiting, p-hydroxyphenylpyruvate hydroxylase becomes the rat limiting step because its activity is inhibited by the accumulation of p-hydroxyphenylpyruvate. For in vivo studies rats were given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase and then injected with a tracer dose of [U- or 1- 14C]tyrosine. Then their respiratory 14CO2 and the incorporation of 14C into total lipids of liver were measured. The amounts of radioactivity in CO2 and lipids were found to be proportional to the tyrosine aminotransferase activity and were not affected by the free tyrosine concentration in the liver. After injection of [U- 14C]acetate the radioactivities in CO2 and lipids were not proportional to the tyrosine aminotransferase activity. These results indicate that the enzyme activity also regulates tyrosine metabolism in vivo. In vivo studied gave no evidence of the participation of p-hydroxyphenylpyruvate hydroxylase in regulation of tyrosine metabolism.
在体外对大鼠肝脏中由酪氨酸生成酮体的过程进行了研究，特别参考了酪氨酸转氨酶（EC 2.6.1.5）和对羟基苯丙酮酸羟化酶（EC 1.14.2.2）的活性。肝脏取自喂食高蛋白饮食或给予皮质醇以诱导不同水平酪氨酸转氨酶的大鼠。将制剂的酶活性与由酪氨酸生成的酮体数量作图。发现在酪氨酸转氨酶活性较低的范围内，活性与生成的酮体数量成正比。然而，超过这个范围，酮体生成不再增加，对羟基苯丙酮酸开始积累。添加抗坏血酸可防止酮体生成的抑制和对羟基苯丙酮酸的积累。这些结果表明，体外调节酪氨酸代谢的主要因素是酪氨酸转氨酶，当该酶活性较高以至于不再是限速因素时，对羟基苯丙酮酸羟化酶成为限速步骤，因为其活性受到对羟基苯丙酮酸积累的抑制。为了进行体内研究，给大鼠喂食高蛋白饮食或给予皮质醇以诱导不同水平的酪氨酸转氨酶，然后注射示踪剂量的[U-或1- 14C]酪氨酸。然后测量它们呼出的14CO2以及14C掺入肝脏总脂质中的情况。发现CO2和脂质中的放射性量与酪氨酸转氨酶活性成正比，且不受肝脏中游离酪氨酸浓度的影响。注射[U- 14C]乙酸盐后，CO2和脂质中的放射性与酪氨酸转氨酶活性不成正比。这些结果表明，该酶活性在体内也调节酪氨酸代谢。体内研究没有证据表明对羟基苯丙酮酸羟化酶参与酪氨酸代谢的调节。
