Abstract：
Hydroxyproline is one of the most prevalent amino acids in animal proteins. It is not a genetically encoded amino acid, but, rather, it is produced by the post-translational modification of proline in collagen, and a few other proteins, by prolyl hydroxylase enzymes. Although this post-translational modification occurs in a limited number of proteins, its biological significance cannot be overestimated. Considering that hydroxyproline cannot be re-incorporated into pro-collagen during translation, it should be catabolized following protein degradation. A cascade of reactions leads to production of two deleterious intermediates: glyoxylate and hydrogen peroxide, which need to be immediately converted. As a result, the enzymes involved in hydroxyproline catabolism are located in specific compartments: mitochondria and peroxisomes. The particular distribution of catabolic enzymes in these compartments, in different species, depends on their dietary habits. Disturbances in hydroxyproline catabolism, due to genetic aberrations, may lead to a severe disease (primary hyperoxaluria), which often impairs kidney function. The basis of this condition is accumulation of glyoxylate and its conversion to oxalate. Since calcium oxalate is insoluble, children with this rare inherited disorder suffer from progressive kidney damage. This condition has been nearly incurable until recently, as significant advances in substrate reduction therapy using small interference RNA led to a breakthrough in primary hyperoxaluria type 1 treatment.
摘要：
羟脯氨酸是动物蛋白中最常见的氨基酸之一。它不是基因编码的氨基酸，但是,更确切地说,它是由胶原蛋白中脯氨酸的翻译后修饰产生的，和其他一些蛋白质，通过脯氨酸羟化酶酶。尽管这种翻译后修饰发生在有限数量的蛋白质中，它的生物学意义不可高估。考虑到羟脯氨酸在翻译过程中不能重新掺入前胶原，它应该在蛋白质降解后被分解代谢。级联反应导致产生两种有害的中间体：乙醛酸和过氧化氢，需要立即转换。因此,参与羟脯氨酸分解代谢的酶位于特定的区室：线粒体和过氧化物酶体。分解代谢酶在这些区室中的特殊分布，在不同的物种中，取决于他们的饮食习惯。羟脯氨酸分解代谢紊乱，由于基因异常，可能导致严重的疾病（原发性高草酸尿症），经常损害肾功能。该条件的基础是乙醛酸盐的积累及其向草酸盐的转化。由于草酸钙是不溶的，患有这种罕见遗传性疾病的儿童患有进行性肾脏损害。直到最近，这种情况几乎无法治愈，因为使用小干扰RNA的底物减少疗法的重大进展导致了原发性高草酸尿症1型治疗的突破。
