Mortimore G E, Schworer C M
Ciba Found Symp. 1979(75):281-305. doi: 10.1002/9780470720585.ch17.
Amino acids appear to be prime regulators of autophagy and proteolysis in liver. They both attain a maximum rapidly when livers from fed rats are perfused in the single-pass mode without amino acids and are suppressed to basal levels by amino acid additions. The fact that their greatest responsiveness to amino acids occurs slightly below normal plasma levels suggests that these cellular processes could play a role in regulating plasma amino acid concentrations in vivo. Autophagy and proteolysis are also inhibited by insulin and stimulated by glucagon. In the latter instance the hormonal action is not direct but mediated indirectly by depletion of intracellular glutamine, probably as a consequence of enhanced gluconeogenesis. Close correlations among (1) rates of intracellular proteolysis, (2) the aggregate volume of lysosomal elements, and (3) estimates of degradable protein internalized within lysosomes indicate that lysosomal function can explain total intracellular protein degradation (with the possible exception of rapidly turning over fractions) over the full range of proteolysis from maximum down to and including the basal state. Since ratios of degradable intralysosomal protein to corresponding rates of proteolysis in intact liver are constant over this range, protein internalization may be the rate-limiting step in lysosomal proteolysis.
氨基酸似乎是肝脏中自噬和蛋白水解的主要调节因子。当以单通道模式灌注无氨基酸的喂食大鼠肝脏时，它们两者都迅速达到最大值，而添加氨基酸后则被抑制至基础水平。它们对氨基酸的最大反应性出现在略低于正常血浆水平的情况，这一事实表明这些细胞过程可能在体内调节血浆氨基酸浓度中发挥作用。自噬和蛋白水解也受到胰岛素的抑制，并被胰高血糖素刺激。在后一种情况下，激素作用不是直接的，而是通过细胞内谷氨酰胺的消耗间接介导的，这可能是糖异生增强的结果。（1）细胞内蛋白水解速率、（2）溶酶体成分的总体积和（3）溶酶体内内化的可降解蛋白估计值之间的密切相关性表明，溶酶体功能可以解释在从最大值到基础状态（包括基础状态）的整个蛋白水解范围内的总细胞内蛋白降解（快速周转部分可能除外）。由于在这个范围内，完整肝脏中溶酶体内可降解蛋白与相应蛋白水解速率的比值是恒定的，蛋白内化可能是溶酶体蛋白水解的限速步骤。
