支链酮酸脱氢酶激酶缺乏症
中文名称
通路描述
支链酮酸脱氢酶激酶缺乏症 (BCKDKD) 是由于支链酮酸脱氢酶激酶 (BCKDK) 突变引起的神经系统疾病 (Joshi 等人，2006; Novarino 等人，2012; Garcia-Cazorla 等人，2014; Tangeraas 等人，2023)。BCKDK 是支链酮酸脱氢酶复合物 (BCKDH) 的负调控因子，该复合物负责支链氨基酸衍生物的氧化脱羧。BCKDK 依赖性对酶 BCKDHA 的 E1 alpha 亚基中丝氨酸残基的磷酸化使 BCKDH 失活 (Popov 等人，1992; Li 等人，2004; Wynn 等人，2004)。BCKDK 失活突变与智力发育受损、小脑发育不全和自闭症相关 (Joshi 等人，2006; Novarino 等人，2012; Garcia-Cazorla 等人，2014; Tangeraas 等人，2023)。与 BCKDK 抑制 BCKDH 活性的作用一致，BCKDK 失活突变导致 BCKDH 活性升高，血浆、组织和尿液中的 BCAAs 减少 (Joshi 等人，2006; Novarino 等人，2012)。BCKDK 缺乏症的症状在通过富含 BCAAs 的饮食补充小鼠模型中得到缓解 (Joshi 等人，2006; Novarino 等人，2012)。
英文描述
Branched-chain ketoacid dehydrogenase kinase deficiency Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurological disorder that arises due to mutations in branched-chain ketoacid dehydrogenase kinase (BCKDK) (Joshi et al 2006; Novarino et al, 2012; Garcia-Cazorla et al, 2014; Tangeraas et al, 2023). BCKDK is a negative regulator of the branched-chain ketoacid dehydrogenase complex (BCKDH), the enzyme responsible for oxidative decarboxylation of branched-chain amino acid derivatives. BCKDK-dependent phosphorylation of serine residues in the E1 alpha subunit of the enzyme BCKDHA inactivates the BCKDH (Popov et al, 1992; Li et al, 2004; Wynn et al, 2004).
Inactivating mutations of BCKDK are associated with impaired intellectual development, microencephaly and autism (Joshi et al 2006; Novarino et al, 2012; Garcia-Cazorla et al, 2014; Tangeraas et al, 2023). Consistent with the role of BCKDK in inhibiting BCKDH activity, inactivating mutations in BCKDK result in higher levels of BCKDH activity and reduced BCAAs in plasma, tissues and urine in mouse models, patients and cell lines (Joshi et al, 2006; Novarino et al, 2012). Symptoms of BCKDK deficiency are alleviated in mouse models by dietary supplementation with a BCAA-enriched diet (Joshi et al, 2006; Novarino et al, 2012).
Inactivating mutations of BCKDK are associated with impaired intellectual development, microencephaly and autism (Joshi et al 2006; Novarino et al, 2012; Garcia-Cazorla et al, 2014; Tangeraas et al, 2023). Consistent with the role of BCKDK in inhibiting BCKDH activity, inactivating mutations in BCKDK result in higher levels of BCKDH activity and reduced BCAAs in plasma, tissues and urine in mouse models, patients and cell lines (Joshi et al, 2006; Novarino et al, 2012). Symptoms of BCKDK deficiency are alleviated in mouse models by dietary supplementation with a BCAA-enriched diet (Joshi et al, 2006; Novarino et al, 2012).
所含基因
4 个基因