纤维蛋白溶解
中文名称
通路描述
纤维蛋白聚集体中的交联多聚体被纤溶酶（一种丝氨酸蛋白酶）分解为可溶性多肽。纤溶酶可由其无活性前体纤溶原生成，并通过两种机制被招募至纤维蛋白聚集体部位：一是与纤维蛋白聚集体表面的组织型纤溶原激活物（tPA）相互作用；二是与细胞表面的尿激酶型纤溶原激活物（uPA）相互作用。第一种机制被认为是血管内溶解血栓的主要机制。第二种机制虽然能介导血栓溶解，但通常主要参与组织重塑、细胞迁移和炎症反应。血栓溶解受两种机制共同调节：首先，高效的纤溶酶激活和纤溶作用仅在聚集体表面或细胞膜上形成的复合物中发生，游离在血液中的蛋白质作为催化剂效率低下且迅速失活。其次，纤溶原激活物和纤溶酶本身均被特定的丝蛋白（serpins）灭活，这些丝蛋白与丝氨酸蛋白酶结合形成稳定的酶促无活性复合物。
英文描述
Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD Mutations in either of the protein subunits of the E1 decarboxylase subcomplex of BCKDH are associated with Maple Syrup Urine Disease 1 (MSUD1).
Mutations of residues in BCKDHA that participate in subunit associations or that form part of the hydrophobic core destabilize the overall assembly of BCKDH and are associated with classic Maple Syrup Urine Disease 1A (Aevarsson et al, 2000; reviewed in Straus et al, 2020; Biswas et al, 2019). Mutations of BCKDHA with less drastic effects on structural stability of the overall BCKDH complex are generally associated with intermediate or intermittent forms of MSUD, and are not annotated in this pathway (reviewed in Strauss et al, 2020)
Mutations in BCKDHB appear to be causative in 35% of MSUD cases(reviewed in Strauss et al, 2020). Classic Maple Syrup Disease 1B is associated with severe loss-of-function mutations in BCKDHB that destabilize the protein interaction interfaces and compromise structural integrity of the complex (reviewed in Straus et al, 2020; Biswas et al, 2019). Less detrimental mutations in BCKDHB are not annotated in this pathway and are generally associated with intermediate or intermittent forms of MSUD (reviewed in Strauss et al, 2020).
Mutations of residues in BCKDHA that participate in subunit associations or that form part of the hydrophobic core destabilize the overall assembly of BCKDH and are associated with classic Maple Syrup Urine Disease 1A (Aevarsson et al, 2000; reviewed in Straus et al, 2020; Biswas et al, 2019). Mutations of BCKDHA with less drastic effects on structural stability of the overall BCKDH complex are generally associated with intermediate or intermittent forms of MSUD, and are not annotated in this pathway (reviewed in Strauss et al, 2020)
Mutations in BCKDHB appear to be causative in 35% of MSUD cases(reviewed in Strauss et al, 2020). Classic Maple Syrup Disease 1B is associated with severe loss-of-function mutations in BCKDHB that destabilize the protein interaction interfaces and compromise structural integrity of the complex (reviewed in Straus et al, 2020; Biswas et al, 2019). Less detrimental mutations in BCKDHB are not annotated in this pathway and are generally associated with intermediate or intermittent forms of MSUD (reviewed in Strauss et al, 2020).
所含基因
3 个基因