Griffith Research Institute for Drug Discovery, Griffith University, Nathan, 4111, Brisbane, Queensland, Australia.
Chem Biol Interact. 2023 Sep 25;383:110679. doi: 10.1016/j.cbi.2023.110679. Epub 2023 Aug 18.
ALDH4A1 genes encode mitochondrial enzymes of delta-1-pyrroline-5-carboxylate metabolism, generating glutamate from either proline or ornithine. Analyses were undertaken of several vertebrate and invertebrate genomes using reported human and mouse ALDH4A1 amino acid sequences. ALDH4A1 sequences and structures were highly conserved, including residues involved in catalysis, coenzyme binding and enzyme structure, previously reported for mouse and human ALDH4A1. The human ALDH4A1 gene contained 15 coding exons and was more highly expressed in human liver and kidney cortex. Vertebrate ALDH4A1 mitochondrial leader sequences exhibited diverse sequences. Phylogeny studies supported the appearance of the ALDH4A1 gene in invertebrate evolution which has been conserved and retained throughout subsequent vertebrate evolution as a single ALDH4A1 gene. Exceptions included polyploidy observed for the Atlantic salmon (Salmo salar) and African toad (Xenopus laevis) genes. An examination of ALDH4A1 sequences from related Drosophila species supported the appearance of a second ALDH4A gene (ALDH4A2) and time dependent evolutionary changes over the past 50 million years for both genes.
ALDH4A1 基因编码线粒体 δ-1-吡咯啉-5-羧酸代谢的酶，可将脯氨酸或鸟氨酸转化为谷氨酸。利用报道的人类和小鼠 ALDH4A1 氨基酸序列，对几种脊椎动物和无脊椎动物的基因组进行了分析。ALDH4A1 序列和结构高度保守，包括先前报道的与小鼠和人类 ALDH4A1 相关的催化、辅酶结合和酶结构的残基。人类 ALDH4A1 基因包含 15 个编码外显子，在人类肝脏和肾脏皮质中表达水平较高。脊椎动物 ALDH4A1 线粒体前导序列表现出不同的序列。系统发育研究支持 ALDH4A1 基因在无脊椎动物进化中的出现，该基因在随后的脊椎动物进化中一直保持保守和保留，作为单个 ALDH4A1 基因存在。例外情况包括大西洋鲑（Salmo salar）和非洲爪蟾（Xenopus laevis）基因的多倍体观察。对相关果蝇物种的 ALDH4A1 序列的检查支持了第二个 ALDH4A 基因（ALDH4A2）的出现，以及这两个基因在过去 5000 万年中随时间发生的进化变化。
