Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The isoprenoid pathway produces three key metabolites--digoxin (membrane Na(+)-K+ ATPase inhibitor, regulator of neurotransmitter transport, and immunomodulatory agent), dolichol (regulatory of N-glycosylation of proteins), and ubiquinone (free-radical scavenger). The pathway was assessed in systemic lupus erythematosis with neuropsychiatric manifestations, slow viral diseases (subacute sclerosing panencephalitis [SSPE], and Creutzfeldt-Jakob disease [CJD]) and patients with recurrent respiratory infections. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with neurolupus, SSPE, and CJD, and in those with right hemispheric dominance. The tryptophan catabolites were increased and the tyrosine catabolites reduced. In these patients the dolichol and glycoconjugate levels were elevated and lysosomal stability was reduced. The ubiquinone levels were low and free-radical levels increased in these patients. The membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with recurrent respiratory infection and left hemispheric dominance, the reverse patterns and hypodigoxinemia with a downregulated isoprenoid pathway were noticed. The isoprenoid pathway is important in the pathogenesis of neurolupus, CJD, SSPE, and recurrent respiratory infections. Hypothalamic digoxin and chemical hemispheric dominance play an important role in the regulation of immunity.
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PMID:Hypothalamic digoxin, hemispheric dominance, and neuroimmune integration. 1232 97

A family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive compulsive disorder, major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa and healthy aging with longevity is described. The family members had hyposexual behavior, less tendency for spirituality, had no insomnia but a tendency towards increased somnolence, no addictive behaviour, had more bonding and affectionate behavior and were less creative with an average IQ. There was no vascular thrombosis, systemic neoplasm and neuronal degeneration in the index family. All members of the family were left hemispheric dominant. The level of serum digoxin, HMG CoA reductase activity and dolichol was found to be decreased in all with a corresponding increase in RBC Na(+)-K(+) ATPase activity and serum ubiquinone magnesium level. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in serum. Total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, glycolipids, activity of GAG degrading enzymes and glycohydrolases were decreased in serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased while cholesterol : phospholipid ratio of membrane decreased. The activity of free radical scavenging enzymes were increased while the concentration of free radicals decreased significantly. The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed.
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PMID:Familial hypodigoxinemic membrane Na(+)-K(+) ATPase upregulatory syndrome - relation between digoxin status and cerebral dominance. 1239 67

The isoprenoid pathway related cascade was assessed in 15 patients with obsessive compulsive disorder (OCD) and la Tourette's syndrome (TS). The pathway was also assessed in right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals to assess whether hemispheric dominance has any correlation with these disease states. The levels of serum digoxin, HMG CoA reductase activity, and dolichol were found to be decreased in OCD and la Tourette's syndrome as well as in left hemispheric dominant individuals with a corresponding increase in RBC Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. There was an increase in tyrosine and its catabolites, and a reduction in tryptophan and its catabolites in the serum. The total and individual glycosaminoglycan (GAG) fractions, carbohydrate residues of glycoproteins, and the concentration of glycolipids decreased in the serum. The activity of GAG degrading enzymes and glycohydrolases were decreased. The RBC membrane glycoconjugates were increased while the membrane cholesterol:phospholipid ratio was decreased. The activity of free radical scavenging enzymes increased while the concentration of free radicals decreased significantly. On the other hand, there was hyperdigoxinemia and the reverse biochemical patterns in those with right hemispheric dominance. Membrane Na(+)-K+ ATPase stimulation can result in decreased intracellular Ca2+ and increased magnesium levels. Increased levels of dopamine can lead to a tic syndrome, while reduced levels of serotonin and increased dopamine can both lead to obsessive compulsive disorder. Decrease in fucose and sialo-ligands, increased immunosuppressive morphine levels, decreased T-cell calcineurin signal transduction related to decreased intracellular calcium, reduced free radical production, and altered presentation of bacterial glycoconjugate antigens can lead to a hypoimmune response and recurrent respiratory infection in OCD patients. OCD and la Tourette's syndrome are associated with left hemispheric chemical dominance.
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PMID:Hypothalamic digoxin deficiency in obsessive compulsive disorder and la Tourette's syndrome. 1242 21

The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin. Digoxin is a steroidal glycoside and could be synthesised by the isoprenoid pathway. The other metabolites of the isoprenoid pathway are cholesterol, dolichol and ubiquinone. We have tried to find out the extent of incorporation of 14C acetate into digoxin in rat brain. The effects of digoxin administration on the rat brain was also studied. The results show that the percentage incorporation of 14C acetate into digoxin is low but detectable. The maximum incorporation was observed for cholesterol, followed by dolichol and finally ubiquinone. The histopathological changes observed after digoxin administration were focal degeneration of the ganglion cells in the cerebrum and cerebellum. The carbohydrate components of the glycoproteins were reduced and the concentration of serotonin, dopamine, and epinephrine showed a significant increase. The role of digoxin in mediating neuronal cell death is discussed.
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PMID:Studies on digoxin--14C-acetate incorporation in to digoxin and degenerative changes in the brain in rats administered digoxin. 1256 15

The hypothalamus produces digoxin, an endogenous membrane Na+-K+ ATPase inhibitor and regulator of neurotransmission. Digoxin being a steroidal glycoside, is synthesised by the isoprenoid pathway. In view of the reports of elevated digoxin levels in metabolic syndrome X with high body mass index, the isoprenoid pathway mediated biochemical cascade was assessed in individuals with high and low body mass index. It was also assessed in individuals with differing hemispheric dominance to find out the relationship between digoxin status, body mass index and hemispheric dominance. The isoprenoid pathway metabolites, tryptophan / tyrosine catabolic patterns and membrane composition were assessed. In individuals with high body mass index an upregulated isoprenoid pathway with increased HMG CoA reductase activity, serum digoxin and dolichol levels and low ubiquinone levels were observed. The RBC membrane Na+-K+ ATPase activity and serum magnesium levels were decreased. The tyrosine catabolites (dopamine, morphine, epinephrine and norepinephrine) were reduced and the tryptophan catabolites (serotonin, quinolinic acid, strychnine and nicotine) were increased. There was an increase in membrane cholesterol : phospholipid ratio and a reduction in membrane glycoconjugates in individuals with high body mass index. The reverse patterns were seen in individuals with low body mass index. The patterns in individuals with high body mass index and low body mass index correlated with right hemispheric dominance and left hemispheric dominance respectively. Hemispheric dominance and digoxin status regulates the differential metabolic pattern observed in individuals with high and low body mass index.
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PMID:Hypothalamic digoxin and regulation of body mass index. 1257 94

The isoprenoid pathway produces 3 key metabolites: digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). The pathway was assessed in patients with human male infertility (oligospermia and decreased motility). It was also studied for comparison in patients with right hemispheric, left hemispheric, and bihemispheric dominance. The results of the study showed that the isoprenoid pathway was upregulated with increased digoxin synthesis in all 3 groups of patients. There was also a reduction in membrane Na(+)-K(+) ATPase activity and serum magnesium levels. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites. The dolichol and glycoconjugate levels increased and lysosomal stability was reduced with increased serum lysosomal enzymes in all 3 groups. The ubiquinone levels were low and free radicals increased. The cholesterol:phospholipid ratio increased and glycoconjugate was reduced in the membrane of these patients. This pattern correlated with those in right hemispheric dominance. The significance of these factors in the pathogenesis of human male infertility is discussed.
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PMID:Isoprenoid pathway dysfunction in human male infertility. 1262 48

The present study assessed the biochemical differences of free radical metabolism and mitochondrial function between right hemispheric dominant and left hemispheric dominant individuals. The following parameters were measured: (1) plasma HMG CoA reductase activity, (2) isoprenoid metabolites--digoxin and ubiquinone, (3) plasma magnesium and RBC membrane Na(+)-K+ ATPase activity; (4) lipid peroxidation products--malondialdehyde, hydroperoxides and conjugated dienes, and NO, (5) reduced glutathione, and (6) activity of superoxide dismutase, catalase, GSH peroxidase, and GSH reductase. The results showed that right hemispheric dominant individuals had (i) increased plasma HMG CoA reductase activity and elevated digoxin levels, (ii) decreased plasma magnesium and RBC membrane Na(+)-K+ ATPase activity, (iii) reduced ubiquinone levels, (iv) with increased levels of lipid peroxidation products and NO, (v) decreased levels of reduced glutathione and free radical scavenging enzymes, and (vi) increased tryptophan and reduced tyrosine levels. Left hemispheric dominant individuals had the opposite patterns. Right hemispheric dominance represents a hyperdigoxinemic state with membrane sodium-potassium ATPase inhibition and increased lipid peroxidation. Left hemispheric dominance represents the reverse pattern with hypodigoxinemic/membrane sodium-potassium ATPase stimulation and decreased lipid peroxidation. Cerebral dominance can regulate mitochondrial function and free radical metabolism.
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PMID:Hypothalamic digoxin, cerebral dominance, and mitochondrial function/free radical metabolism. 1265 94

The hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor and regulator of neurotransmission, digoxin. Digoxin, a steroidal glycoside, is synthesized by the isoprenoid pathway. In view of the reports of elevated digoxin levels in metabolic syndrome X with high body mass index, the isoprenoid-mediated pathway biochemical cascade was assessed in individuals with high and low body mass index. It was also assessed in individuals with differing hemispheric dominance to find out the relationship among digoxin status, body mass index, and hemispheric dominance. The isoprenoid pathway metabolites, tryptophan/tyrosine catabolic patterns, glycoconjugate, and free radical metabolism, as well as membrane composition, were assessed. In individuals with high body mass index, an upregulated isoprenoid pathway with increased digoxin levels, increased glycoconjugates, and dolichol levels, reduced lysosomal stability, low ubiquinone levels with increased free radical generation, and increased membrane cholesterol:phospholipid ratio were observed. The reverse patterns were seen in individuals with a low body mass index. The patterns in individuals with a high body mass index and low body mass index correlated with right hemispheric dominance and left hemispheric dominance, respectively. Hemispheric dominance and digoxin status regulated the differential metabolic pattern observed in individuals with high and low body mass index. Hypothalamic digoxin/cerebral dominance can regulate the metabolic/endocrine function, as well as the structure/function of cellular organalle.
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PMID:Hypothalamic digoxin, hemispheric chemical dominance, and endocrine/metabolic/cellular regulation. 1265 95

The role of the isoprenoid pathway in gastrointestinal and hepatic diseases, and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with (i) acid peptic disease, (ii) ulcerative colitis, (iii) gallstones, (iv) cryptogenic cirrhosis liver, (v) Reye's syndrome, (vi) mesenteric artery occlusion, (vii) irritable bowel syndrome, and (viii) in individuals with right hemispheric, left hemispheric, and bihemispheric dominance: 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; 2. tryptophan/tyrosine catabolic patterns; 3. free radical metabolism; 4. glycoconjugate metabolism; and 5. membrane composition. In patients with gastrointestinal and hepatic disease there were elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites in the serum. There was an increase in cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in these groups of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. An upregulated isoprenoid pathway and hyperdigoxinemia is characteristic of gastrointestinal and hepatic disease and in right hemispheric chemical dominance. Right hemispheric chemical dominance is important in deciding the predisposition to gastrointestinal and hepatic disease.
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PMID:Hypothalamic digoxin, cerebral chemical dominance, and regulation of gastrointestinal/hepatic function. 1269 Oct 2

The present study assessed the biochemical differences in lipid metabolism between right hemispheric dominant and left hemispheric dominant individuals. The HMG CoA reductase activity and the serum isoprenoidal metabolities--digoxin, dolichol, and ubiquinone--were studied. The results showed that right hemispheric dominant individuals had (i) increased HMG CoA reductase activity, (ii) elevated serum digoxin levels, (iii) reduced serum ubiquinone levels, (iv) increased serum tryptophan and reduced tyrosine, (v) increased serum dolichol levels, and (vi) decreased RBC membrane Na(+)-K+ ATPase activity and serum magnesium levels. Left hemispheric dominant individuals had the opposite patterns. Right hemispheric dominance represents a hyperdigoxinemic state with membrane sodium-potassium ATPase inhibition and an upregulated isoprenoid pathway. Left hemispheric dominance represents the reverse pattern with hypodigoxinemia/membrane sodium-potassium ATPase stimulation and a downregulated isoprenoid pathway. Cerebral dominance can regulate lipid metabolism.
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PMID:Hypothalamic digoxin, cerebral dominance, and lipid metabolism. 1269 Oct 3


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