Accumulation of d -2-hydroxyglutarate (D-2-HG) and/or l -2-hydroxyglutarate (L-2-HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge gathered on 2-hydroxyglutaric acidurias (2-HGA), since the description of the first patients in 1980.

2021年1月12日 · D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) into 2-oxoglutarate, and genetic D-2-HGDH deficiency leads...

2016年9月16日 · In addition to synthesis, 2-HG levels are regulated by a pair of dehydrogenases that convert 2-HG back to α-KG (i.e. l-2-HGDH and d-2-HGDH). Mutations in these enzymes manifest as the hydroxyglutaric acidurias, devastating inherited metabolic diseases with symptoms including epilepsy and cerebellar ataxia ( 8 9 , 10 11 ).

2021年1月12日 · This work reports the crystal structures of human D-2-HGDH in apo form and in complexes with D-2-HG, D-malate, D-lactate, L-2-HG, and 2-oxoglutarate, respectively. D-2-HGDH comprises a FAD-binding domain, a substrate-binding domain, and a …

L-2-hydroxyglutaric aciduria (L-2-HGA), a neurometabolic disorder caused by mutations in the L-2 hydroxyglutarate dehydrogenase (L-2-HGDH) gene, presents with psychomotor retardation, cerebellar ataxia, extrapyramidal symptoms, macrocephaly and seizures.

我们可以证明hD2HGDH是一种FAD依赖性蛋白，它能够催化D-2HG和D-乳酸分别氧化为α-酮戊二酸和丙酮酸。 获得了这两种变体作为载脂蛋白，因此具有催化活性。 FAD的添加无法恢复变体的酶活性，表明辅因子结合位点被单个氨基酸替代所损害。 进一步的分析表明，两种变体均形成聚集体，这些聚集体显然无法结合FAD辅助因子。 由于D-2-羟基戊二酸尿症也可能是由于ETF或其下游电子受体ETF-泛醌氧化还原酶的功能丧失而引起的，因此ETF可以充当还原的hD2HGDH的同 …

Chiral 2-hydroxyglutarates (2-OHG) are important molecular signatures of their specific biochemical pathways and inborn errors of metabolism, for both healthy and diseased biological cells. For example, the TCA cycle of a cancer cell showing the buildup of 2 …

2021年1月13日 · 该工作揭示了人源FAD依赖的D-2-羟戊二酸脱氢酶（D-2-HGDH）对底物特异性识别和催化反应的分子机制，阐述了D-2-HGDH突变体在遗传学疾病D-2-羟戊二酸尿酸症发生中的作用。 2-羟戊二酸（2-HG）是正常细胞代谢过程中一些酶促反应的副产物，根据连有羟基的第二位碳原子的手性不同，分为D型和L型。 体内2-HG的过度积累会导致2-羟基戊二酸尿症（2-HGA），并与多种恶性肿瘤相关。 人线粒体中存在二种功能酶—D-和L-2-HG脱氢酶（D-和L …

2012年3月6日 · Accumulation of D-2-hydroxyglutarate (D-2-HG) and/or L-2-hydroxyglutarate (L-2-HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge...

2012年3月6日 · Accumulation of d -2-hydroxyglutarate (D-2-HG) and/or l -2-hydroxyglutarate (L-2-HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge gathered on 2-hydroxyglutaric acidurias (2-HGA), since the description of the first patients in 1980.