Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosinase (EC 1.14.18.1)/O2, ceruloplasmin (human type X)/O2, and peroxidase (EC 1.11.1.7)/H2O2 oxidized the endogenous central nervous system alkaloid salsolinol (SAL) at physiological pH. The proximate oxidation product was an electrophilic ortho-quinone (4) which at pH 7.0 rapidly tautomerized. Four major initial products were formed from 4: cis- and trans-1,2,3,4-tetrahydro-1-methyl-4,6,7-isoquinolinetriol (A and B, respectively), 2,3,4-trihydro-1-methyl-7-hydroxy-6-oxyisoquinoline (C), and 1-methyl-6,7-isoquinoline diol (D). Mechanisms describing the formation of these products have been presented. Ortho-quinone 4, formed in the enzyme-mediated reactions, was rapidly attacked by glutathione to yield the 5-S-, 8-S-, and 5,8-bi-S-glutathionyl conjugates of SAL. Preliminary experiments indicated that injection of A, B and C into the CNS of mice evoked profound behavioral effects. Quinone methide C was toxic. The potential role of the oxidation of salsolinol in the neurodegenerative and behavioral effects associated with chronic alcoholism is discussed.
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PMID:Interactions of salsolinol with oxidative enzymes. 165 22

The electrochemical oxidation of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1) has been studied in neutral aqueous solution at a pyrolytic graphite electrode (PGE). Voltammograms of 1 show two closely spaced oxidation peaks, Ia and IIa. At potentials less positive than the peak potential (Ep) for peak Ia, 1 is oxidized to a radical intermediate which dimerizes to give two diastereomers of 5,5'-bi(1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline) (5 and 6). At potentials more positive than Ep for peak Ia the putative radical intermediate is further electrooxidized to a C(5)-centered carbocation which reacts with 1 in an ion-substrate reaction to give 5 and 6 or with water to give, ultimately, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (12). Dimers 5 and 6 give two reversible oxidation peaks at the PGE, the second of which corresponds to peak IIa observed in voltammograms of 1. Because 5 and 6 are easily oxidizable compounds they are only observed as products in the initial stages of the controlled potential electrooxidation of 1. Tyrosinase/O2, human ceruloplasmin/O2, and peroxidase/H2O2 also oxidize 1 to 5, 6, and 12 as the initial products. In the presence of glutathione the electrochemically driven and enzyme-mediated oxidations of 1 result in the formation of 5-S-glutathionyl-1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline as a major product. Central administration of diastereomer 5 or 6 to mice evoked behavioral responses similar to those caused by the opioid analgesics. These behavioral effects, which include spatial disorientation and a characteristic ducklike walk, became most pronounced approximately 3 h after drug administration and continued for about 3 days. Neurotransmitter and related metabolite analyses of whole brain reveal that 5 and 6 cause a general increase in dopaminergic and serotonergic activity and a small but significant decrease in cholinergic activity. These transmitter/metabolite disturbances appear to parallel the time course of the observed behavioral effects. The possible roles of in vivo oxidations of 1, an alkaloid which is elevated in mammalian brain following ethanol consumption, in the addictive, behavioral, and neurodegenerative consequences of chronic alcoholism are discussed.
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PMID:Oxidation chemistry and biochemistry of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline. 173 36

Prealbumin, albumin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, ceruloplasmin, haptoglobin, transferrin, IgG, IgM and IgA were studied in blood serum of healthy donors and of patients with chronic alcoholism by means of cross immuno-electrophoresis and immunodiffusion. Only content of alpha 1-antitrypsin was distinctly altered in blood serum of the patients with alcoholism as compared with normal state, while individual variations in content of the proteins studied were considerably higher in blood serum of the patients. At the same time, distinct dissimilarity of the patterns studied was found between healthy donors and patients with chronic alcoholism when concentration ratios of some positively and negatively charged acute phase proteins were calculated (alpha 1-antitrypsin/albumin, haptoglobin/albumin, haptoglobin/transferrin).
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PMID:[An analysis of blood serum proteins in chronic alcoholism patients by a cross immunoelectrophoresis method]. 277 78

The concentrations of the enzymatically active and immunoreactive ceruloplasmin (CP) were determined in the blood serum of healthy men by means of the spectrophotometric and immuno-electro-photometric methods. Part of the total (immunoreactive) CP (15%), circulated in the blood channel in an enzymatically inactive state. The increase of the time of suffering from chronic alcoholism from 1 to 29 years leads to the growth of the concentrations of CP possessing enzymatic activity and of immunoreactive CP. The share of the enzymatically inactive protein remains practically constant. During acute alcohol intoxication there is a temporal drop of the C1 share in enzymatically active state with a constant concentration of the total protein in the blood serum.
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PMID:[Ceruloplasmin activity and content of the blood of persons with acute and chronic alcoholic intoxication]. 300 32

In the guinea pigs with experimental alcoholism lower ceruloplasmin activity than in normal animals has been found in blood serum. In vitro neither ethanol nor acetaldehyde (10(-6)M--10(-3)M) influenced ceruloplasmin activity. A possible mechanism of ethanol-induced alterations is discussed.
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PMID:Ethanol-induced alterations in ceruloplasmin activity. 653 56

The repeated intake of a great amount of ethanol is followed by functional and organic changes in the body. The intestinal absorption of alcohol is accompanied by an increased absorption of Gram negative bacteria endotoxins in the portal blood. In the liver, endotoxins stimulate CD14 receptors on the membrane of Kupffer cells, with a secondary inflammatory liver response, consisting in the secretion of proinflammatory cytokines and acute phase proteins. Simultaneously, alcohol metabolism in the hepatocytes by alcohol dehydrogenase, microsomal enzymes and catalase pathways determines a large production of ROS (reactive oxygen species), with secondary oxidative aggression on all liver cells: hepatocytes, Kupffer cells, endothelial sinusoidal cells, hepatic stellate cells and liver s lymphocytes. The oxidative aggression, as well as the intermediary products of the alcohol metabolism, cause a structural change of the antigenic structures of the liver and of the released proteins, that induces an immune response on the both pathways (humoral and cellular). The pathophysiological mechanisms and the paraclinical characteristics of the ethanol-induced liver failure are well known, so we were interested to study the patients with chronic alcoholism, but no clinical or paraclinical sign of liver failure, in order to describe the liver's protective mechanisms. For this reason, 153 patients with chronic alcoholism were divided into four test lots, in order to determine: the activity and the serum level of ceruloplasmin, plasma level of MDA (malondialdehyde), lactic and pyruvic acids, serum level of transferrin, alpha1-antitrypsin, CRP (C reactive protein), C3 fraction of the complement, IgA, IgG, IgM, IL-1beta, IL-6 and IL-8, cytosolic level of the cytochrome c in the circulating leukocytes. An immunophenotype study (as normal markers) on the peripheral blood lymphocytes was performed, too. The results demonstrate an important oxidative aggression induced by three sources: the alcohol metabolism in the hepatocytes, activated Kupffer cells and activated neutrophils that have infiltrated the liver, due to the chemoattractant effect of IL-8. This aggression induces apoptosis and necrosis of the liver cells. The major liver protective factor is, in our opinion, IL-6, due to its important antioxidant, antiapoptotic and proregenerative demonstrated actions. This protective effect of IL-6 is accompanied by antioxidant and antiprotease actions of ceruloplasmin, alpha1-antitrypsin and transferrin. We consider that an increased serum level of IL-6 accompanied by a decreased level of IL-1beta signify that antiapoptotic, antioxidant and proregenerative liver mechanisms prevail against proapoptotic and necrotic mechanisms. On the other hand, the ethanol-induced apoptosis of leukocytes (especially of the B cells) is very important, probably due to the absence of IL-6 protective action on these cells. The apoptosis of the circulating leukocytes is proved by their significant increase of the cytochrome c cytosolic level. The ethanol-induced liver immune response is predominantly cellular, as proved by the decreased ratio T helper (CD4+)/T cytotoxic (CD8+) in the peripheral blood. It is very important to observe that these significant immunologic changes appear before clinical or paraclinical signs of hepatic failure start. All these parameters were investigated in three groups of patients: chronic alcoholics, chronic alcoholics in the first 24 hours of the withdrawal and chronic alcoholics with acute alcohol intoxication, so the aggression types and the protective mechanisms were measured and differentiated in each "ethanolic status".
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PMID:Ethanol-induced dysfunction of hepatocytes and leukocytes in patients without liver failure. 1629 18

A 58-year-old patient, without any notable medical history, except for alcoholism and treated hypertension, developed anemia and leukopenia with macrocytosis. Folate deficiency was diagnosed and subsequently treated. Despite folate supplementation, the hematological parameters did not normalize. Further diagnosis investigations were led to search for uncommon etiologies of anemia and leukoneutropenia. We diagnosed severe copper deficiency on the basis of decreased plasma levels of copper and ceruloplasmin. Copper supplementation improved blood counts within three months. This case illustrates hematological disorders due to copper deficiency, initially masked by an associated folate deficiency. The copper deficiency etiology was not identified in this case.
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PMID:[An uncommon etiology of anemia: copper deficiency]. 2390 80

Oral cancer with high incidence rates is occurring in many countries including in India, Pakistan, Bangladesh, Sri Lanka and Taiwan. Smoking, alcoholism, and betel nut chewing are considered to be the main risk factors for oral cancer. Further, deaths from oral cancer have increased year by year. Although several oral cancer-associated biomarkers have been reported, very few useful biomarkers have been applied for early diagnosis. Therefore, the investigation of oral cancer-specific biomarkers is urgently needed. We previously investigated N-glycomes of oral cancer cells and patient plasma. We found that both mRNA levels of FUT8 and core-fucosylated glycoproteins increase in cases of oral cancer relative to normal cases. In this study we aim to discover novel core-fucosylated glycoprotein biomarkers for oral cancer diagnosis with glycoproteomic approaches. First, forty plasma samples obtained from the Human Bioinformation Bank of NCKUH were subjected to AAL (Aleuria aurantia lectin) affinity chromatography. Core-fucosylated proteins were collected and applied for LC-MS/MS followed by electrophoresis. Fourteen proteins were identified, and expression levels of proteins in plasma were verified by western blot. Expression levels of some glycoproteins were elevated in the oral cancer group, including ceruloplasmin, haptoglobin, and leucin-rich alpha-2-glycoprotein 1 (LRG1). However, levels of some glycoproteins decreased in the cancer group, including apolipoprotein A-I (apo A-I) and apolipoprotein A-IV (apo A-IV). Via ELISA analysis, we found that apo A-IV and apo A-IV/total protein ratios were decreased in plasma accompanied with cancer stages. The LRG1/total protein ratio was found to increase while plasma levels of LRG1 were not found to differ between the oral cancer plasma and normal groups. An ROC curve analysis reveals strong diagnosis performance when combining apo A-IV levels and LRG1/total protein ratios. Taken together, apo A-IV and LRG1, given their strong performance in detecting oral cancer, can serve as useful biomarkers and may be used as a useful tool for oral cancer screening and early diagnosis.
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PMID:Glycoproteomic identification of novel plasma biomarkers for oral cancer. 3098 19