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

Measurements were taken of the activity of glutamate dehydrogenase (GDH) and the levels of transmitter amino acids in anatomically dissected regions of cervical and lumbar spinal cord in eight patients dying with amyotrophic lateral sclerosis (ALS) and in 11 neurologically normal controls. GDH activity was considerably increased in lateral and ventral white matter and in the dorsal horn of the ALS cervical spinal cord, but normal in the ventral horn and the dorsal columns. Similar, although less pronounced, GDH changes were found in the lumbar enlargement. The mean concentrations of aspartate and glutamate were reduced in all regions of ALS spinal cord investigated. Taurine concentrations were significantly increased in several subdivisions of cervical spinal cord, but normal in lumbar regions. Glycine levels were significantly reduced in lumbar ventral and dorsal horns. There was no striking change in spinal cord GABA levels in our ALS patients. It is suggested that the reduced levels of glutamate and aspartate as well as the elevated GDH activity in the spinal cord of ALS patients may reflect an overactivity of the neurons releasing these potentially excitotoxic amino acids and thus may be causally related to the spinal neuro-degenerative changes characteristic of ALS.
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PMID:Amyotrophic lateral sclerosis: glutamate dehydrogenase and transmitter amino acids in the spinal cord. 168 99

A 44-year-old patient died from amyotrophic lateral sclerosis (ALS) after nine years of heavy exposure to cadmium (Cd) in a nickel cadmium (Ni-Cd) battery factory. Two years after starting work he and co-workers had experienced pruritus, loss of smell, nasal congestion, nosebleeds, cough, shortness of breath, severe headaches, bone pain, and proteinuria. Upper back pain and muscle weakness progressed to flaccid paralysis. EMG findings were consistent with motor neuron disease. Cd impairs the blood-brain barrier, reduces levels of brain copper-zinc (Cu-Zn) superoxide dismutase (SOD), and enhances excitoxicity of glutamate via up-regulation of glutamate dehydrogenase and down-regulation of glutamate uptake in glial cells. High levels of methallothionein, a sign of exposure to heavy metals, have been found in brain tissue of deceased ALS patients. The effects of Cd on enzyme systems that mediate neurotoxicity and motor neuron disease suggest a cause effect relationship between Cd and ALS in this worker.
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PMID:Amyotrophic lateral sclerosis in a battery-factory worker exposed to cadmium. 1137 40

Sporadic Amyotrophic Lateral Sclerosis (SALS) is a fatal neurologic disease characterized by degeneration of motor neurons in the spinal cord, brainstem and cortex. While familial cases of ALS exist, the sporadic form accounts for the majority of adult-onset cases. It has been hypothesized that the neurodegenerative mechanisms underlying SALS might arise from glutamate-mediated excitotoxicity and mitochondrial dysfunction. Studies on autopsied SALS spinal cord and brain have reported decreased cytochrome oxidase activity, decreased astrocytic glutamate-transporter protein, and alterations of glutamate levels and glutamate metabolizing enzyme activities. We conjectured that if alterations in glutamate metabolism and cytochrome oxidase activity occur in the SALS central nervous system these alterations may also be manifested in peripheral tissues such as platelets in living SALS patients. In this study we compared the activities of cytochrome oxidase, citrate synthase, glutamate dehydrogenase and glutaminase in platelets from SALS and control subjects. We found that there were no differences in any of the enzyme activities measured between the two groups. Our data argue against generalized ubiquitous biochemical alterations of these enzymes in SALS patients.
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PMID:Unaltered cytochrome oxidase, glutamate dehydrogenase and glutaminase activities in platelets from patients with sporadic amyotrophic lateral sclerosis--a study of potential pathogenetic mechanisms in neurodegenerative diseases. 1145 96

One of the hypotheses in amyotrophic lateral sclerosis (ALS) indicates on excitatory amino acids as the cause of neuronal death. Changes in their concentration in the tissues and body fluids may be the consequence of a defect in their transport, as well as abnormal activities of glutamate metabolizing enzymes. Abnormal synthesis/degradation of these enzymes and/or influence of activators/inhibitors should be taken into account. The activity of enzymes of glutamate metabolism of rat spinal cord in vitro in the presence of serum and cerebrospinal fluid (CSF) of 20 patients with ALS and 20 healthy controls was tested. In the presence of serum of the ALS patients glutaminase was significantly stimulated, instead of being inhibited; the inhibition of GABA aminotransferase, glutamate decaboxylase and aspartate aminotransferase was less evident than in the controls, glutamate dehydrogenase lost its activity more than in control conditions, the inhibition of glutamine synthetase was comparable to that when normal serum was applied. The activity of the enzymes in the presence of CSF of ALS patients was generally similar to that of normal CSF, except of glutaminase which was stimulated and GABA aminotransferase, which was inhibited stronger than in the presence of normal CSF. This study indicates, that changes in glutamate concentration in tissues and body fluids in ALS may be caused, at least partly, by abnormalities in the activity of glutamate metabolism enzymes, which are in turn induced by neurotoxic agents present in body fluids of ALS patients.
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PMID:[Neurotoxic activity of serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients against some enzymes of glutamate metabolism]. 1173 83