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Hexokinase

内分泌

关键词内分泌 临床研究术语 糖类

词汇介绍

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解析

hexokinase   英 /,heksəu'kaineis/

释    义   n. [生化] 己糖激酶

例    句   Hexokinase (HXK) plays a important role in sugar signaling of plant cell.己糖激酶在植物细胞的信号转导中起着重要的作用。

概述

概述


己糖激酶是一种酶的磷酸化的己糖(六碳糖),己糖形成磷酸盐。己糖激酶具有将无机磷酸基团从ATP转移至底物的能力。不应将己糖激酶与葡萄糖激酶混淆,后者是己糖激酶的特定同工型。所有的己糖激酶都能够使几种己糖磷酸化,但是葡萄糖激酶的底物亲和力降低了50倍,其主要的己糖底物是葡萄糖。己糖(例如葡萄糖)的磷酸化通常将其限制在许多细胞内代谢过程中,例如糖酵解或糖原合成。


哺乳动物己糖激酶的类型


有四种重要的哺乳动物己糖激酶同工酶(EC 2.7.1.1),它们被称为己糖激酶I,II,III和IV或己糖激酶A,B,C和D。己糖激酶I,II和III被称为“低Km”同工酶,因为它对葡萄糖具有很高的亲和力(低于1 mM)。己糖激酶IV(“葡萄糖激酶”)哺乳动物己糖激酶IV,也称为葡萄糖激酶,在动力学和功能上与其他己糖激酶不同。所述的位置磷酸化在亚细胞水平时发生葡糖激酶之间易位细胞质和细胞核的肝细胞。如果该底物的浓度足够高,葡萄糖激酶只能使葡萄糖磷酸化。其葡萄糖的Km比己糖激酶I,II和III高100倍。糖激酶IV为单体,约50kD,与葡萄糖表现出正协同作用,并且不受其产物6-磷酸葡萄糖的变构抑制。己糖激酶IV存在于肝脏,胰腺,下丘脑,小肠以及某些其他神经内分泌细胞中,并在碳水化合物代谢中起重要的调节作用。


与线粒体的联系


己糖激酶I和II可通过与孔蛋白或电压依赖性阴离子通道的特异性结合而物理结合到线粒体外膜的外表面。这种联系使己糖激酶直接进入由线粒体产生的ATP,线粒体是己糖激酶的两种底物之一。线粒体己糖激酶在迅速生长的恶性肿瘤细胞中高度升高,其水平比正常组织高200倍。线粒体结合的己糖激酶已被证明是在肿瘤细胞中有氧代谢的极高糖酵解速率的驱动力。

Type 2 diabetes differentially affects the substrate saturation kinetic attributes of erythrocyte hexokinase and phosphofructokinase复制标题

2型糖尿病不同程度地影响红细胞己糖激酶和磷酸果糖激酶的底物饱和动力学属性

发表时间:2019-09-14

影响指数:2.7

作者: Sunita Bhise

期刊:FEBS Letters

Diabetes is characterized by hyperglycemia with impaired utilization of glucose, which results from either low levels of insulin (type 1 diabetes) or insulin resistance as in type 2 diabetes, ultimately leading to diabetic complications such as retinopathy, nephropathy, cardiomyopathy, and neuropathy starting with micro-and macroangiopathies. More recently it has also been noted that the red blood cells (RBCs) from type 2 diabetic patients show significantly altered characteristics. These include changes in the shape, loss of deformability, and decreased half-life, which leads to fragmentation. The former two changes are believed to be a contributory factor associated with micro- and macroangiopathies. Interactions of spectrin with ATP are believed to be the critical factor controlling deformability of the RBCs. In the RBCs, glycolysis is the only metabolic pathway for ATP generation. The glycolytic flux is tightly controlled by the reactions catalyzed by hexokinase (HK; EC 2.7.1.1), phosphofructokinase (PFK; EC 2.7.1.11), and pyruvate kinase (PK; EC 2.7.1.40), the steps that are virtually irreversible. It has also been reported that the intracellular concentrations of intermediates of glycolysis change significantly in the RBCs of diabetic patients. Additionally, lactic acidosis is a prominent feature of diabetes. In our earlier studies, we have observed that the activities of major enzymes of glycolysis in erythrocytes of type 2 diabetic subjects were significantly altered with remarkable increase in HK and substantial decrease in PFK activity. We also noted that the lactate dehydrogenase (LDH; EC 1.1.1.27) activity in erythrocytes of type 2 diabetic subjects increased with significant alterations in kinetic properties, which is conducive to conversion of pyruvate to lactate leading to lactic acidosis. In view of the above, it was of interest to find out whether the kinetic properties of the two key enzymes, that is, HK and PFK, are also influenced by the diabetic state since this will have bearing on ATP synthesis. The results of these investigations are summarized in the present communication.

译文

糖尿病的特点是高血糖和葡萄糖利用受损,这是由于胰岛素水平低(1型糖尿病)或胰岛素抵抗(如2型糖尿病),最终导致糖尿病并发症,如视网膜病变、肾病、心肌病和以微血管和大血管病变开始的神经病变。最近还注意到,2型糖尿病患者的红细胞(RBCs)表现出显著的变化特征。这些变化包括形状的改变,变形能力的丧失,以及半衰期的缩短,从而导致碎片化。前两种改变被认为是与微血管病和大血管病相关的一个因素。spectrin与ATP的相互作用被认为是控制红细胞变形能力的关键因素。在红细胞中,糖酵解是产生ATP的唯一代谢途径。糖酵解通量受到己糖激酶(HK;EC 2.7.1.1)、磷酸果糖激酶(PFK;ec2.7.1.11)和丙酮酸激酶(PK;ec2.7.1.40)催化的反应的严格控制,这些反应几乎是不可逆的。糖尿病患者红细胞内糖酵解中间产物的浓度也有显著变化。此外,乳酸性酸中毒是糖尿病的一个显著特征。 在我们早期的研究中,我们观察到2型糖尿病患者红细胞糖酵解主要酶的活性显著改变,HK显著升高,PFK活性显著降低。我们还注意到,2型糖尿病受试者红细胞乳酸脱氢酶(LDH;EC 1.1.1.27)活性增加,动力学性质发生显著变化,有利于丙酮酸转化为乳酸导致乳酸酸中毒。鉴于上述情况,我们有兴趣了解两种关键酶(HK和PFK)的动力学特性是否也受糖尿病状态的影响,因为这将影响ATP的合成。本文概述了这些调查的结果。

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