第09章物质代谢的联系及调节2013-Fen-ban.pptVIP

* Regulation of gene expression by class I hormones. Steroid hormones readily gain access to the cytoplasmic compartment of target cells. Glucocorticoid hormones (solid triangles) encounter their cognate receptor in the cytoplasm, where it exists in a complex with heat shock protein 90 (hsp). Ligand binding causes dissociation of hsp and a conformational change of the receptor. The receptor?ligand complex then traverses the nuclear membrane and binds to DNA with specificity and high affinity at a glucocorticoid response element (GRE). This event triggers the assembly of a number of transcription coregulators (+ ), and enhanced transcription ensues. By contrast, thyroid hormones and retinoic acid directly enter the nucleus, where their cognate receptors are already bound to the appropriate response elements with an associated transcription repressor complex (? ). This complex, which consists of molecules such as N-CoR or SMRT in the absence of ligand, actively inhibits transcription. Ligand binding results in dissociation of the repressor complex from the receptor, allowing an activator complex to assemble. The gene is then actively transcribed. 2．调节细胞酶含量也可通过改变酶蛋白降解速度 通过改变酶蛋白分子的降解速度，也能调节酶的含量。 溶酶体 蛋白酶体 —— 释放蛋白水解酶，降解蛋白质 —— 泛素识别、结合蛋白质； 蛋白水解酶降解蛋白质 proteosome lysosome 内、外环境改变 机体相关组织分泌激素 激素与靶细胞上的受体(receptor)结合 靶细胞产生生物学效应，适应内外环境改变 激素作用机制： 二、激素通过作用特异受体调节代谢过程 (组织、效应特异性) 激素分类 Ι 膜受体激素:(亲水性)胰岛素、生长激素、促甲状腺激素、 甲状旁腺素 等蛋白质内激素，生长因子等肽类 及肾上腺素等儿茶酚胺类激素。 Ⅱ 胞内受体激素：（疏水性）类固醇激素、甲状腺素、 1,25(OH)2-维生素D3 等 按激素受体在细胞的部位不同 1．膜受体激素信号通过跨膜受体传递调节细胞代谢 激素作用方式： 2．激素-胞内受体复合物可影响基因转录调节细胞代谢 甲状腺激素 糖皮质激素 Glucocorticoid response element (GRE) Thyroid hormone response element (TRE) 受体 受体 （一）糖、脂和蛋白质代谢在不同饥饿状态有不同改变 糖原消耗 血糖趋于降低 胰岛素分泌减少 胰高血糖素分泌增加 引起一系列的代谢变化 1.短期饥饿时脂肪动员增加而减少糖的利用 三、机体通过神经系统及神经-体液途径整体调节体内物质代谢 （1～3天） （1）脂代谢变化 脂肪动员加强，酮体生成增多 （2）糖代谢变化 （3）蛋白质代谢变化 肌蛋白质分解加强，氨基酸(Ala,Gln)异生成糖 肝糖异生加强，(aa’、乳酸、甘油) 组织对葡萄糖利用降低（心、