Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic indicators of glucose and lipid metabolism, i.e. glucose turnover, insulin concentration in plasma, insulin clearance, concentrations of non-esterified fatty acids (NEFA), glycerol and potassium were investigated in nine ewes during three reproductive states in order to examine their importance for development of subclinical ketosis. The increase of insulin in plasma was measured after a continuous 60 min intravenous infusion of glucose (4.9 mmol.min-1). Turnover of glucose and insulin clearance were quantified during a combined euglycemic, hyperinsulinemic clamp. Insulin was consecutively infused in doses of 5 and 10 mU.kg-1.min-1 for about 2 1/2 hours, each. Plasma glucose concentration was adjusted to 5.3 to 5.8 mmol.l-1. The experiments were carried out during non-pregnancy and non-lactation, 4 weeks to 3 days before lambing and 3 to 4 weeks after lambing, each during normo- and hypocalcemia. Hypocalcemia (0.9 to 1.0 mmol Ca2+.l-1) was induced by continuous i.v. infusion of a 5% Na-EDTA solution. Infusion rate was continuously adjusted. The glucose induced increase in plasma insulin concentration was significantly lower during late pregnancy compared to peak lactation and non-pregnancy (46.3, 62.4 and 128 mU.l-1, respectively). The insulin clearance during a hyperinsulinemic clamp with 5 mU.kg-1.min-1 was significantly less during late pregnancy compared to peak lactation and non-pregnancy (3.7, 6.0, 4.8 ml.kg-1.min-1, respectively). The concentrations of NEFA and glycerol in plasma during the infusion of 5 mU insulin.kg-1.min-1 were significantly higher during late pregnancy than during non-pregnancy (NEFA: 0.41, 0.04 mmol.l-1; glycerol: 96, 29 mumol.l-1, respectively). The results showed that insulin responsiveness was significantly reduced in sheep during late pregnancy. The insulin-mediated uptake of glucose by muscle and fat tissues and the insulin-mediated inhibition of lipolysis were significantly reduced during late pregnancy compared to non-pregnancy and lactation. The diminished responsiveness of target tissue towards insulin during late pregnancy predisposed the animals for development of subclinical ketosis. Hypocalcemia exaggerated this situation by its inhibitory effect on hepatic gluconeogenesis and by enhancing insulin resistance of target tissues. The factors which are responsible for the altered responsiveness of target tissues towards insulin during late pregnancy are yet unknown. The potassium concentration in plasma showed a proportional increase with increase of the energy deficit of the target tissues. This effect could have been exerted by a decrease in cellular concentration of ATP and a concomitant reduction of the activity of Na(+)-K(+)-ATPase. The indicators of glucose and lipid metabolism which were examined in this study showed marked individual variation, particularly during late pregnancy. The marked changes of these indicators with reproductive stages as well as their great variation between individual sheep support the assumption that they are of significance for the development of pregnancy toxemia in sheep.
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PMID:[Effect of insulin on glucose and and fat metabolism in ewes during various reproductive states in normal and hypocalcemia]. 941 Jul 23

Fanconi-Bickel syndrome is a rare autosomal-recessive disorder caused by mutations in the SLC2A2 gene coding for the glucose transporter protein 2 (GLUT2). Major manifestations include hepatomegaly, glucose intolerance, post-prandial hypoglycaemia and renal disease that usually presents as proximal tubular acidosis associated with proximal tubule dysfunction (renal Fanconi syndrome). We report a patient harbouring a homozygous mutation of SLC2A2 who presented a dramatic exacerbation of metabolic acidosis in the context of a viral infection, owing to both ketosis and major urinary bicarbonate loss. The kidney biopsy revealed nuclear and cytoplasmic accumulation of glycogen in proximal tubule cells, a lack of expression of GLUT2, and major defects of key proteins of the proximal tubule such as megalin, cubilin and the B2 subunit of H(+)-ATPase. These profound alterations of the transport systems most likely contributed to proximal tubule alterations and profound bicarbonate loss.
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PMID:Acute metabolic acidosis in a GLUT2-deficient patient with Fanconi-Bickel syndrome: new pathophysiology insights. 2516 76

Ketosis is a metabolic state in which the body uses ketones derived from breakdown of fatty acids as the primary mitochondrial fuel source instead of glucose. In recent years an accumulation of evidence for the beneficial effects of the ketotic state on the brain have heightened interest in its potential for use in neurological conditions. The ketogenic diet (KD) induces ketosis and is an effective treatment for medically resistant epilepsy. There is significant comorbidity between epilepsy and bipolar disorder (BD) and both conditions are treated by anti-convulsant drugs. In addition, reports on bipolar disease online fora have highlighted subjective mood stabilization effects associated with the KD. These KD reported effects could be explained if there was a disorder in the conversion of pyruvate into Acetyl-CoA (and subsequent impairment of oxidative phosphorylation) which was bypassed by ketones providing an alternative substrate for oxidative phosphorylation. This is consistent with growing evidence that mitochondrial dysfunction plays a causal role in BD and explains the reported TCA cycle dysfunction and elevated pyruvate levels in BD. Reduced levels of ATP affects the normal operation of the Na, K-ATPase in the brain with differing levels of reduction either leading to reduced neuronal action potential and inhibition of neurotransmitter release (consistent with the depressed state in BD) or increased neuronal resting potential and hyper-excitability (consistent with a [hypo]manic mood state). We hypothesize that the mitochondrial dysfunction is due to a disorder of the Pyruvate Dehydrogenase Complex (PDC) and/or Mitochondrial Carrier Protein (MCP) shuttle which moves intracellular pyruvate into mitochondria. The resultant reduction in ATP generation could explain mood instability and cycling in BD (through mechanisms such as those delineated by Mallakh and Peters). This proposed novel causal pathway could explain mood de-stabilization in BD and the reported positive effects of KD. If true, this hypothesis would suggest that there should be increased research attention to PDC (and in particular the E1 alpha subunit) as potential therapeutic targets and further study of a possible role of KD in BD to improve mood stability. Experimental approaches, such as through a clinical trial of KD on mood stabilization in BD, are required to further investigate this hypothesis.
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PMID:A pyruvate dehydrogenase complex disorder hypothesis for bipolar disorder. 3138 31

Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson's disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone-glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate-glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.
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PMID:Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders. 3209 91