D-α-Hydroxyglutaric Acid

D-α-Hydroxyglutaric acid (D-2-HG) is an α-hydroxy acid that is over-produced in the human neurometabolic disease D-2-hydroxyglutaric aciduria (D-2-HGA). It is normally synthesized from 2-ketoglutarate (2-KG) by hydroxyacid-oxoacid transhydrogenase (HOT), although defects in HOT are not known to be associated with D-2-HGA. Instead, type I D-2-HGA involves mutations in D-2-hydroxyglutarate dehydrogenase, which converts D-2-HG back to 2-KG. Type II D-2-HGA results from gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), causing it to supplement HOT in converting 2-KG to D-2-HG. In bacteria, this α-hydroxy acid may be synthesized from oxalate and propionyl-coenzyme A by an α-hydroxyglutaric acid synthetase.

D-α-羟基戊二酸（D-2-HG）是一种α-羟基酸，在人类神经代谢疾病D-2-羟基戊二酸尿症（D-2-HGA）中过度产生。它通常由羟酸-酮酸转氢酶（HOT）从2-酮戊二酸（2-KG）合成，尽管HOT缺陷不被认为与D-2-HGA有关。相反，I型D-2-HGA涉及D-2-羟基戊二酸脱氢酶的突变，该酶将D-2-HG转化为2-KG。II型D-2-HGA是由异柠檬酸脱氢酶2（IDH2）中的功能增强突变导致的，它使其在将2-KG转化为D-2-HG的过程中辅助HOT。在细菌中，这种α-羟基酸可以通过α-羟基戊二酸合成酶从草酸和丙酰辅酶A合成。