Hjelmqvist L, Norin A, El-Ahmad M, Griffiths W, Jörnvall H
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Cell Mol Life Sci. 2003 Sep;60(9):2009-16. doi: 10.1007/s00018-003-3287-1.
Alcohol dehydrogenases (ADHs) of the MDR type (medium-chain dehydrogenases/reductases) have diverged into two evolutionary groups in eukaryotes: a set of 'constant' enzymes (class III) typical of basal enzymes, and a set of 'variable' enzymes (remaining classes) suggesting 'evolving' forms. The variable set has larger overall variability, different segment variability, and variability also in functional segments. Using a major aldehyde dehydrogenase (ALDH) from cod liver and fish ALDHs deduced from the draft genome sequence of Fugu rubripes (Japanese puffer fish), we found that ALDHs form more complex patterns than the ADHs. Nevertheless, ALDHs also group into 'constant' and 'variable' sets, have separate segment variabilities, and distinct functions. Betaine ALDH (class 9 ALDH) is 'constant,' has three segments of variability, all non-functional, and a limited fish/human divergence, reminiscent of the ADH class III pattern. Enzymatic properties of fish betaine ALDH were also determined. Although all ALDH patterns are still not known, overall patterns are related to those of ADH, and group separations may be distinguished. The results can be interpreted functionally, support ALDH isozyme distinctions, and assign properties to the multiplicities of the ADH and ALDH enzymes.
多药耐药型（中链脱氢酶/还原酶）酒精脱氢酶（ADHs）在真核生物中已分化为两个进化组：一组是基础酶典型的“恒定”酶（III类），另一组是表明“进化”形式的“可变”酶（其余类别）。可变组具有更大的整体变异性、不同的片段变异性以及功能片段的变异性。利用来自鳕鱼肝的一种主要醛脱氢酶（ALDH）以及从红鳍东方鲀（日本河豚）基因组草图序列推导的鱼类ALDHs，我们发现ALDHs形成的模式比ADHs更复杂。然而，ALDHs也分为“恒定”和“可变”组，具有各自独立的片段变异性和不同的功能。甜菜碱ALDH（9类ALDH）是“恒定”的，有三个可变片段，均无功能，且鱼类/人类的差异有限，这让人联想到ADH III类模式。我们还测定了鱼类甜菜碱ALDH的酶学性质。尽管并非所有的ALDH模式都已明确，但总体模式与ADH的模式相关，并且可以区分组间差异。这些结果可以从功能上进行解释，支持ALDH同工酶的区分，并为ADH和ALDH酶的多样性赋予特性。
