Plaitakis A, Nicklas W J, Desnick R J
Ann Neurol. 1980 Apr;7(4):297-303. doi: 10.1002/ana.410070403.
Four nicotinamide-adenine dinucleotide phosphate-requiring enzymes were measured in disrupted cultured skin fibroblasts from a 19-year-old patient with juvenile onset of a spinocerebellar and extrapyramidal syndrome. There was marked reduction in the activity of glutamate dehydrogenase (GDH) (22% of mean control activity); GDH activity was also decreased in homogenates of leukocytes from this patient (38% of mean control activity). GDH activity was measured in the leukocytes of two siblings afflicted with adult-onset spinocerebellar syndrome and found to be decreased in both (29% and 31% of mean control activity); an unaffected sibling had normal GDH activity. Mixing experiments with control fibroblast and leukocyte homogenates did not show the presence of a GDH inhibitor in cells from these patients. This allosterically regulated enzyme was stimulated by adenosine 5'-diphosphate (10(-3) M) and inhibited by guanosine 5'-triphosphate (10(-3) M) in both fibroblast and leukocyte homogenates; these changes occurred in equal proportions in the patients and controls. The decreased fibroblast and leukocyte GDH activity persisted at different concentrations of the enzyme's substrates and with successive passages of cultured fibroblasts. GDH may have an important role in the metabolism of glutamate, a putative neurotransmitter in cerebellum, brainstem, and spinal cord. A genetic deficiency of GDH may underlie some forms of spinocerebellar ataxias.
在一名患有少年型脊髓小脑和锥体外系综合征的19岁患者的培养皮肤成纤维细胞匀浆中，检测了四种需要烟酰胺腺嘌呤二核苷酸磷酸的酶。谷氨酸脱氢酶（GDH）活性显著降低（为平均对照活性的22%）；该患者白细胞匀浆中的GDH活性也降低（为平均对照活性的38%）。在两名患有成人型脊髓小脑综合征的同胞的白细胞中检测了GDH活性，发现二者均降低（分别为平均对照活性的29%和31%）；一名未受影响的同胞的GDH活性正常。将对照成纤维细胞和白细胞匀浆进行混合实验，未显示这些患者的细胞中存在GDH抑制剂。在成纤维细胞和白细胞匀浆中，这种别构调节酶受到5'-二磷酸腺苷（10⁻³ M）的刺激，并受到5'-三磷酸鸟苷（10⁻³ M）的抑制；患者和对照中的这些变化比例相同。在不同浓度的该酶底物条件下以及培养的成纤维细胞连续传代后，成纤维细胞和白细胞中降低的GDH活性仍然存在。GDH可能在谷氨酸代谢中起重要作用，谷氨酸是小脑、脑干和脊髓中一种假定的神经递质。GDH的基因缺陷可能是某些形式的脊髓小脑共济失调的基础。
