Terlecky Stanley R, Koepke Jay I, Walton Paul A
Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, Michigan 48201, USA.
Biochim Biophys Acta. 2006 Dec;1763(12):1749-54. doi: 10.1016/j.bbamcr.2006.08.017. Epub 2006 Aug 23.
Peroxisomes are indispensable for proper functioning of human cells. They efficiently compartmentalize enzymes responsible for a number of metabolic processes, including the absolutely essential beta-oxidation of specific fatty acid chains. These and other oxidative reactions produce hydrogen peroxide, which is, in most instances, immediately processed in situ to water and oxygen. The responsible peroxidase is the heme-containing tetrameric enzyme, catalase. What has emerged in recent years is that there are circumstances in which the tightly regulated balance of hydrogen peroxide producing and degrading activities in peroxisomes is upset-leading to the net production and accumulation of hydrogen peroxide and downstream reactive oxygen species. The factor most essentially involved is catalase, which is missorted in aging, missing or present at reduced levels in certain disease states, and inactivated in response to exposure to specific xenobiotics. The overall goal of this review is to summarize the molecular events associated with the development and advancement of peroxisomal hypocatalasemia and to describe its effects on cells. In addition, results of recent efforts to increase levels of peroxisomal catalase and restore oxidative balance in cells will be discussed.
过氧化物酶体对于人类细胞的正常功能不可或缺。它们有效地分隔了负责多种代谢过程的酶，包括特定脂肪酸链至关重要的β-氧化。这些以及其他氧化反应会产生过氧化氢，在大多数情况下，过氧化氢会立即在原位被处理为水和氧气。负责此过程的过氧化物酶是含血红素的四聚体酶——过氧化氢酶。近年来发现，在某些情况下，过氧化物酶体中过氧化氢生成和降解活性的严格调控平衡会被打破，导致过氧化氢以及下游活性氧的净生成和积累。最关键的因素是过氧化氢酶，它在衰老过程中分拣错误，在某些疾病状态下缺失或水平降低，并在接触特定异生物质时失活。本综述的总体目标是总结与过氧化物酶体过氧化氢酶血症的发生和发展相关的分子事件，并描述其对细胞的影响。此外，还将讨论最近为提高过氧化物酶体过氧化氢酶水平和恢复细胞内氧化平衡所做努力的结果。
