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)

Carnitine deficiency can be defined as a decrease of intracellular carnitine, leading to an accumulation of acyl-CoA esters and an inhibition of acyl-transport via the mitochondrial inner membrane. This may cause disease by the following processes. A. Inhibition of the mitochondrial oxidation of long-chain fatty acids during fasting causes heart or liver failure. The latter may cause encephalopathy by hypoketonaemia, hypoglycaemia and hyperammonaemia. B. Increased acyl-CoA esters inhibit many enzymes and carriers. Long-chain acyl-CoA affects mitochondrial oxidative phosphorylation at the adenine nucleotide carrier, and also inhibits other mitochondrial enzymes such as glutamate dehydrogenase, carnitine acetyltransferase and NAD(P) transhydrogenase. C. Accumulation of triacylglycerols in organs increases stress susceptibility by an exaggerated response to hormonal stimuli. D. Decreased mitochondrial acetyl-export lowers acetylcholine synthesis in the nervous system. Primary carnitine deficiency can be defined as a genetic defect in the transport or biosynthesis of carnitine. Until now only defects at the level of carnitine transport have been discovered. The most severe form of primary carnitine deficiency is the consequence of a lesion of the carnitine transport protein in the brush border membrane of the renal tubules. This defect causes cardiomyopathy or hepatic encephalopathy usually in combination with skeletal myopathy. In a patient with cardiomyopathy and without myopathy, we found that carnitine transport at the level of the small intestinal epithelial brush border was also inhibited. The patient was cured by carnitine supplementation. Muscle carnitine increased, but remained too low. This suggests that carnitine transport in muscle is also inhibited. Carnitine transport in fibroblasts was normal, which disagrees with literature reports for similar patients.
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PMID:Primary carnitine deficiency. 219 96

The behavior of the principal NADPH-consuming pathways, fatty acid synthesis (-ATP-citrate lyase), transhydrogenase, glutamate dehydrogenase, glutathione reductase, NADPH-cytochrome c reductase and mitochondrial and cytoplasmic thioredoxin reductases were studied during the development of the heart, brain and liver of the rat. The liver is the tissue with highest NADPH-consuming activities. Transhydrogenase activity is highest in the heart; it undergoes two steep increases of activity, one at birth and another between 15 and 25 days. Liver cytoplasmic glutathione reductase activity increases mainly at birth. The activities in heart and brain are lower and the brain enzyme activity slightly increases throughout development. Liver NADPH-cytochrome c reductase activity greatly increases at weaning. The heart activity is the lowest, no changes taking place in the developmental period. Heart mitochondrial and brain cytoplasmic thioredoxin reductases undergo increases in activity at birth. The ratios of NADPH-producing/NADPH-consuming activities are constant in all tissues studied, and oscillate between congruent to 4 in fetuses to congruent to 2 in adults, the only exception being the adult heart ratio (congruent to 23). This otherwise constancy confirms that both processes are closely correlated.
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PMID:Development of NADPH-consuming pathways in heart, brain and liver of the rat. 640 38

L-Threonine, a kind of essential amino acid, has numerous applications in food, pharmaceutical, and aquaculture industries. Fermentative l-threonine production from glucose has been achieved in Escherichia coli. However, there are still several limiting factors hindering further improvement of l-threonine productivity, such as the conflict between cell growth and production, byproduct accumulation, and insufficient availability of cofactors (adenosine triphosphate, NADH, and NADPH). Here, a metabolic modification strategy of two-stage carbon distribution and cofactor generation was proposed to address the above challenges in E. coli THRD, an l-threonine producing strain. The glycolytic fluxes towards tricarboxylic acid cycle were increased in growth stage through heterologous expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and citrate synthase, leading to improved glucose utilization and growth performance. In the production stage, the carbon flux was redirected into l-threonine synthetic pathway via a synthetic genetic circuit. Meanwhile, to sustain the transaminase reaction for l-threonine production, we developed an l-glutamate and NADPH generation system through overexpression of glutamate dehydrogenase, formate dehydrogenase, and pyridine nucleotide transhydrogenase. This strategy not only exhibited 2.02- and 1.21-fold increase in l-threonine production in shake flask and bioreactor fermentation, respectively, but had potential to be applied in the production of many other desired oxaloacetate derivatives, especially those involving cofactor reactions.
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PMID:Two-stage carbon distribution and cofactor generation for improving l-threonine production of Escherichia coli. 3025 40