Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 39 normal subjects, 32 neurological controls, 66 patients with progressive ataxic disorders, 32 with multiple system atrophy, 40 with Parkinson's disease, eight with Steele-Richardson-Olszewski syndrome, eight with juvenile Parkinsonism and four with the dystonia-Parkinsonism syndrome. GDH activity was reproducible to within 10% in leukocyte pellets stored at -70 degrees C for up to 9 months, and did not vary with sex or age in control subjects. There was marked variation in the relative proportions of heat stable and heat labile forms of GDH between control subjects and on repeated assay in the same subject. Total leukocyte GDH activity was similar in normal subjects and neurological controls. Mean total GDH activity was reduced in all patient groups by between 15 to 29% compared with controls. Fourteen patients had total GDH activity below 50% of the control mean, but low values were not specific for any one disease (five had ataxic disorders, four Parkinson's disease, three multiple system atrophy, one juvenile Parkinsonism, and one dystonia-Parkinsonism). The heat labile fraction of GDH represented about 20% of total activity in control subjects, and 27% in the patients with reduced total GDH activity. Thus low GDH activity was not disease-specific in this study, and the heat-labile GDH fraction was not selectively affected. "Reduced" leucocyte GDH activity in some patients may represent no more than the lower end of a normal distribution.
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PMID:Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders. 320 97

Recent data from our laboratory have shown a regionally specific increase in lipid peroxidation in postmortem progressive supranuclear palsy (PSP) brain. To extend this finding, we measured activities of mitochondrial enzymes as well as tissue malondialdehyde (MDA) levels in postmortem superior frontal cortex (Brodmann's area 9; SFC) from 14 pathologically confirmed cases of PSP and 13 age-matched control brains. Significant decreases (-39%) in alpha-ketoglutarate dehydrogenase complex/glutamate dehydrogenase ratio and significant increases (+36%) in tissue MDA levels were observed in the SFC in PSP; no differences in complex I or complex IV activities were detected. Together, these results suggest that mitochondrial dysfunction and lipid peroxidation may underlie the frontal metabolic and functional deficits observed in PSP.
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PMID:Frontal lobe dysfunction in progressive supranuclear palsy: evidence for oxidative stress and mitochondrial impairment. 1064 41

Abnormalities in energy metabolism and oxidative stress accompany many neurodegenerative diseases, including progressive supranuclear palsy (PSP). Previously, we showed decreased activities of a mitochondrial enzyme complex, alpha-ketoglutarate dehydrogenase complex (KGDHC), and marked increases in tissue malondialdehyde levels in post-mortem superior frontal cortex from the patients with PSP. The current study demonstrates that KGDHC is also significantly diminished (-58%) in the cerebellum from patients with PSP (n = 14), compared to age-matched control brains (n = 13). In contrast to cortex, markers of oxidative stress, such as malondialdehyde, tyrosine nitration or general protein carbonyl modification, did not increase in cerebellum. Furthermore, the protein levels of the individual components of KGDHC did not decline. The activities of two other mitochondrial enzymes were measured to determine whether the changes in KGDHC were selective. The activity of aconitase, a mitochondrial enzyme with an iron/sulfur cluster, is also significantly diminished (-50%), whereas glutamate dehydrogenase activity is unchanged. The present results suggest that the interaction of metabolic impairment and oxidative stress is region-specific in PSP brain. In cerebellum, reductions in KGDHC occur in the absence of increases in common measures of oxidative stress, and may underlie the metabolic deficits and contribute to pathological and clinical manifestation related to the cerebellum in patients with PSP.
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PMID:Mitochondrial impairment in the cerebellum of the patients with progressive supranuclear palsy. 1174 33