Hayward B E, Bonthron D T
Human Genetics Unit, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, UK.
Eur J Biochem. 1998 Oct 1;257(1):85-91. doi: 10.1046/j.1432-1327.1998.2570085.x.
Ketohexokinase (fructokinase, KHK) catalyses the phosphorylation of fructose to fructose-l-phosphate. It thereby initiates the intracellular catabolism of a large proportion of dietary carbohydrate. Although found at high level in liver, renal cortex and small intestine, fructokinase activity has also been known for many years to be present at lower levels in most other tissues. We previously found that there appeared to be two isoforms of human KHK, and have now investigated the molecular basis for this in human, rat and mouse. Cloning of the human KHK gene, on chromosome 2p23.2-2p23.3, shows that it has nine exons, spanning 14 kb. An intragenic duplication has resulted in two similar 135-bp exons (designated 3a and 3c), separated by a short intron. Exon 3a and exon 3c are mutually exclusively spliced into KHK mRNA. This exon-intron structure and the pattern of alternative splicing are conserved in both the rat and mouse, suggesting distinct conserved functions for the two KHK isoforms. The alternative splicing is also tissue specific, since in both rat and human, tissues expressing high levels of KHK (liver, kidney and duodenum) utilise exclusively the 3c exon, while other tissues use only 3a. Furthermore, comparison of human foetal and adult tissues indicates a developmental splicing shift from use of exon 3a to exon 3c.
己酮糖激酶（果糖激酶，KHK）催化果糖磷酸化生成1-磷酸果糖。由此启动了大部分膳食碳水化合物的细胞内分解代谢。尽管在肝脏、肾皮质和小肠中含量较高，但多年来人们也知道果糖激酶活性在大多数其他组织中的水平较低。我们之前发现人类KHK似乎有两种同工型，现在我们对人类、大鼠和小鼠中这种现象的分子基础进行了研究。位于2号染色体p23.2 - p23.3区域的人类KHK基因克隆显示，它有9个外显子，跨度为14 kb。基因内重复产生了两个相似的135 bp外显子（命名为3a和3c），中间由一个短内含子隔开。外显子3a和外显子3c相互排斥地剪接到KHK mRNA中。这种外显子 - 内含子结构和可变剪接模式在大鼠和小鼠中都是保守的，这表明两种KHK同工型具有不同的保守功能。可变剪接也是组织特异性的，因为在大鼠和人类中，表达高水平KHK的组织（肝脏、肾脏和十二指肠）只使用外显子3c，而其他组织只使用3a。此外，人类胎儿组织和成人组织的比较表明存在从使用外显子3a到外显子3c的发育性剪接转变。
