HEME OXYGENASE - FUNCTION, MULTIPLICITY, REGULATORY MECHANISMS, AND CLINICAL-APPLICATIONS
HEME OXYGENASE - FUNCTION, MULTIPLICITY, REGULATORY MECHANISMS, AND CLINICAL-APPLICATIONS
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DOI：
10.1096/fasebj.2.10.3290025
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发表时间：
1988-07-01
期刊：
影响因子：
4.8
通讯作者：
MAINES, MD
中科院分区：
文献类型：
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作者：
MAINES, MD
在生物系统中，血红素的氧化是由微粒体中的两种同工酶HO-1和HO-2来实现的。HO-1是众所周知的一种血红素加氧酶，它的活性可以在多种刺激(金属、血红素、激素等)的刺激下被诱导100倍。HO-2是最近才发现的，同工酶似乎是不可诱导的。这两种形式是两种不同基因的产物，在组织表达上也不同。HO-1的一级结构与91个氨基酸残基的HO-2片段的同源性仅为58%，但二级结构同源性为100%。这一区域被认为是催化中心。最有可能的是，HO-1基因的调控方式与该基因中的金属硫蛋白相同。HO-1有一个热休克调节元件，可能还有许多启动子元件，它们与各自的诱导剂结合，导致基因的转录。在体内，HO-1活性的诱导伴随着总P-450水平的降低，在重组系统中，细胞色素P-450血红素可以被HO-1和HO-2定量地转化为胆绿素。在体内，锌和锡原卟啉结合后，酶活性被抑制了很长一段时间。这一特性似乎有助于抑制胆红素的产生。然而，金属卟啉并不是无害的，会对细胞新陈代谢造成重大干扰。在这篇综述中，重点介绍了关于血红素加氧酶的最新发现。Maines，M.D.血红素加氧酶：功能、多样性、调节机制和临床应用。FASE B J.2：2557-2568；1988。
In biological systems oxidation of heme is carried out by two isozymes of the microsomal heme oxygenase, HO‐1 and HO‐2. HO‐1 is the commonly known heme oxygenase, the activity of which can be induced by up to 100‐fold in response to a wide variety of stimuli (metals, heme, hormones, etc.). HO‐2 was only recently discovered, and the isozyme appears to be uninducible. The two forms are products of two different genes and differ in their tissue expression. The primary structure of HO‐1 and an HO‐2 fragment of 91 amino acid residues show only 58% homology, but share a region with 100% secondary structure homology. This region is believed to be the catalytic site. Most likely, HO‐1 gene is regulated in the same manner as metallothione in the gene. HO‐1 has a heat shock regulatory element, and possibly many promoter elements, which bind to respective inducers and cause transcription of the gene. In vivo induction of HO‐1 activity in the liver is accompanied by decreases in the total P‐450 levels and, in a reconstituted system, cytochrome P‐450bheme can be quantitatively converted to biliverdin by HO‐1 and HO‐2. The enzyme activity is inhibited in vivo for extended periods subsequent to binding of Zn‐and Sn‐ protoporphyrins. This property appears useful for the suppression of bilirubin production. The metalloporphyrins, however, are not innocuous and cause major disruptions in cellular metabolism. In this review recent findings on heme oxygenase are highlighted.— Maines, M. D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications.FASEB J.2: 2557‐2568; 1988.