Mommsen Thomas P
Department of Biology, University of Victoria, PO Box 3020, Victoria, BC V8W 3P5, Canada.
Comp Biochem Physiol B Biochem Mol Biol. 2004 Nov;139(3):383-400. doi: 10.1016/j.cbpc.2004.09.018.
The August Krogh principle, stating that for any particular question in biology, nature holds an ideal study system, was applied by choosing the anorexic, long-distance migration of salmon as a model to analyze protein degradation and amino acid metabolism. Reexamining an original study done over 20 years ago on migrating sockeye salmon (Oncorhynchus nerka), data on fish migration and starvation are reviewed and a general model is developed on how fish deal with muscle proteolysis. It is shown that lysosomal activation and degradation of muscle protein by lysosomal cathepsins, especially cathepsin D and sometimes cathepsin L, are responsible for the degradation of muscle protein during fish migration, maturation and starvation. This strategy is quite the opposite to mammalian muscle wasting, including starvation, uremia, cancer and others, where the ATP-ubiquitin proteasome in conjunction with ancillary systems, constitutes the overwhelming pathway for protein degradation in muscle. In mammals, the lysosome plays a bit part, if any. In contrast, the proteasome plays at best a subordinate role in muscle degradation in piscine systems. This diverging strategy is put into the context of fish metabolism in general, with its high amino acid turnover, reliance on amino acids as oxidative substrates and flux of amino acids from muscle via the liver into gonads during maturation. Brief focus is placed on structure, function and evolution of the key player in fishes: cathepsin D. The gene structure of piscine cathepsin D is outlined, focusing on the existence of duplicate, paralogous, cathepsin D genes in some species and analyzing the relationship between a female and liver-specific aspartyl protease and fish cathepsin Ds. Evolutionary relationships are developed between different groups of piscine cathepsins, aspartyl proteases and other cathepsins. Finally, based on specific changes in muscle enzymes in fish, including migrating salmon, common strategies of amino acid and carbon flux in fish muscle are pointed out, predicting some metabolic concepts that would make ideal application grounds for the August Krogh principle.
奥古斯特·克罗格原理指出，对于生物学中的任何特定问题，自然界都存在一个理想的研究系统。通过选择鲑鱼厌食性的长途洄游作为模型来分析蛋白质降解和氨基酸代谢，该原理得以应用。重新审视20多年前对洄游红大马哈鱼（Oncorhynchus nerka）所做的一项原始研究，回顾了有关鱼类洄游和饥饿的数据，并建立了一个关于鱼类如何处理肌肉蛋白水解的通用模型。结果表明，溶酶体的激活以及溶酶体组织蛋白酶（尤其是组织蛋白酶D，有时还有组织蛋白酶L）对肌肉蛋白的降解，是鱼类洄游、成熟和饥饿期间肌肉蛋白降解的原因。这种策略与哺乳动物的肌肉萎缩情况截然相反，在哺乳动物的肌肉萎缩（包括饥饿、尿毒症、癌症等）中，ATP-泛素蛋白酶体与辅助系统共同构成了肌肉中蛋白质降解的主要途径。在哺乳动物中，溶酶体即便有作用，也是微不足道的。相比之下，蛋白酶体在鱼类系统的肌肉降解中充其量只起次要作用。这种不同的策略被置于鱼类新陈代谢的大背景下，鱼类新陈代谢具有高氨基酸周转率、依赖氨基酸作为氧化底物以及在成熟过程中氨基酸从肌肉经肝脏流入性腺的特点。简要聚焦于鱼类中的关键参与者——组织蛋白酶D的结构、功能和进化。概述了鱼类组织蛋白酶D的基因结构，重点关注某些物种中重复的、旁系同源的组织蛋白酶D基因的存在，并分析了一种雌性和肝脏特异性天冬氨酸蛋白酶与鱼类组织蛋白酶D之间的关系。建立了不同鱼类组织蛋白酶、天冬氨酸蛋白酶和其他组织蛋白酶组之间的进化关系。最后，基于鱼类（包括洄游鲑鱼）肌肉酶的特定变化，指出了鱼类肌肉中氨基酸和碳通量的常见策略，预测了一些代谢概念，这些概念将成为奥古斯特·克罗格原理的理想应用基础。
