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Title
Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease.

Author
Heafield MT; Fearn S; Steventon GB; Waring RH; Williams AC; Sturman SG

Source
Neurosci Lett, 1990 Mar, 110:1-2, 216-20

Abstract
Elevated plasma cysteine to sulphate ratios were found in patients with Motor neurone disease (MND), Parkinson's disease (PD) and Alzheimer's disease (AD). Cysteine and sulphate were measured by colourimetric methods. Following recent discovery of a defect in sulphoxidation and sulphation of xenobiotics in these diseases, this finding confirms that endogenous sulphur metabolism is disturbed.The mean cysteine:sulphate ratios (x 10(3] in fasting early morning plasma were 506, 521 and 477 for MND, PD and AD whereas it was 96 for normal controls (P less than 0.001).This excess of cysteine thiol groups may interfere with neural protein function. The deficiency of sulphate ions may lead to reduced xenobiotic detoxification.

Title
Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo.

Author
Bella DL; Hirschberger LL; Hosokawa Y; Stipanuk MH

Source
Am J Physiol, 1999 Feb, 276:2 Pt 1, E326-35

Abstract
Little is known about mechanisms of regulation of cysteine dioxygenase (CDO), gamma-glutamylcysteine synthetase (GCS), and cysteine-sulfinate decarboxylase (CSDC) in response to diet. Enzyme activity and Western and Northern or dot blot analyses were conducted on liver samples from rats fed a basal low protein diet or diets with graded levels of protein or methionine for 2 wk. Higher levels of CDO activity and CDO protein but not of CDO mRNA were observed in liver of rats fed methionine or protein-supplemented diets, indicating that CDO activity is regulated by changes in enzyme concentration.Lower concentrations of the heavy or catalytic subunit of GCS (GCS-HS) mRNA and protein, as well as a lower activity state of GCS-HS in rats fed methionine- or protein-supplemented diets, indicated that dietary regulation of GCS occurs by both pretranslational and posttranslational mechanisms.Lower CSDC activity, CSDC protein concentration, and CSDC mRNA concentration were found in rats fed the highest level of protein, and regulation appeared to involve changes in mRNA concentration. Regulation of key enzymes of cysteine metabolism in response to diet determines the use of cysteine for synthesis of its essential metabolites.

Title
High levels of dietary protein or methionine have different effects on cysteine metabolism in rat hepatocytes.

Author
Bella DL; Stipanuk MH

Source
Adv Exp Med Biol, 1996, 403:, 73-84

Abstract
This study clearly indicates that relatively high levels of both CDO and CSAD activity are needed for substantial taurine synthesis and that protein and methionine supplementation, at equimolar sulfur amino acid levels, are not equivalent in terms of their effects on cysteine catabolic enzyme activities and cysteine metabolism in hepatocytes. Evidence for a reciprocal regulation of cysteine catabolism (or CDO activity) and GSH synthesis (or gamma-glutamylcysteine synthetase activity) in rat liver was also obtained. Although very high levels of protein and methionine were fed in this study, previous studies with lower levels of protein or methionine showed similar changes in cysteine metabolism. Several questions regarding regulation of cysteine metabolism remain unanswered. Beyond sulfur amino acid availability, animals fed high protein diets appear to have other signals for regulation of CDO and CSAD activities. These signals may be related to the different hormonal and metabolic state of these animals. Furthermore, little is known about the molecular mechanisms involved in the observed changes in CDO and CSAD activities. The association between CDO activity and CDO protein has not been evaluated. Jerkins and Steele, using immunochemical detection and quantification of CSAD protein in rat liver, showed that changes in CSAD protein concentration were correlated to changes in CSAD activity. The exact mechanisms or direct effectors which bring about changes in CDO and CSAD activities have yet to be determined. Further exploration of these potential regulatory mechanisms needs to be conducted to better understand the response of cysteine sulfinate-dependent cysteine catabolism to high levels of dietary protein or sulfur amino acids.

Title
Sulphoxidation and sulphation capacity in patients with primary biliary cirrhosis

Author
Davies MH; Ngong JM; Pean A; Vickers CR; Waring RH; Elias E

Source
J Hepatol, 1995 May, 22:5, 551-60

Abstract
We have previously reported an association of impaired S-oxidation with primary biliary cirrhosis. In order to confirm and further define this relationship, we retested S-oxidation capacity via three metabolic pathways and sulphation capacity via a fourth pathway. Metabolism of S-carboxymethyl-L-cysteine is polymorphic -20% of healthy individuals being poor S-oxidisers. We found 26% with primary biliary cirrhosis were poor S-oxidisers, compared with 36% with other liver disease and 25% of healthy controls. Differences were not statistically significant. S-oxidation of ranitidine is dependent upon flavin mono-oxygenases. We showed a non-significant trend toward less S-oxide in primary biliary cirrhosis and other liver disease, compared with healthy controls, with no significant difference between disease groups. Conversion of cysteine to sulphate depends predominantly on cysteine dioxygenase. Impaired activity may be reflected by decreased plasma sulphate and elevated cysteine. We found that the plasma cysteine: sulphate ratio was significantly elevated not only in primary biliary cirrhosis (p < 0.0001), but also in other liver disease (p < 0.0001), compared with healthy individuals. Sulphation capacity was studied by analysing paracetamol metabolism. Paracetamol sulphate and sulphate: glucuronide ratio were reduced in primary biliary cirrhosis compared with normal individuals, (p < 0.05).A trend towards less sulphate in primary biliary cirrhosis compared other liver disease was not significant (p = 0.42). We conclude that although sulphation and some sulphoxidation pathways are impaired in primary biliary cirrhosis, we can currently find no evidence to substantiate the hypothesis that primary biliary cirrhosis is a disease specifically associated with poor S-oxidation, as assessed via these metabolic pathways.

Title
Abnormal sulphur oxidation in systemic lupus erythematosus

Author
Gordon C; Bradley H; Waring RH; Emery P

Source
Lancet, 1992 Jan, 339:8784, 25-6

Abstract
S-carboxy-L-methylcysteine was used to assess the activity of the S-oxidation pathway of sulphur metabolism in 35 patients with systemic lupus erythematosus (SLE); 25 (71%) showed impaired sulphoxidation and 21 (60%) produced virtually no sulphoxides, compared with 17 (36%) and 2 (4%), respectively, of 47 healthy controls. The substrate/product ratio of cysteine oxygenase (plasma cysteine/sulphate) was significantly higher in SLE patients than in controls (median [interquartile range] 362 [224-588] vs 65 [44-111]; p less than 0.00001). The alternative pathway of sulphur metabolism, S-methylation, catalysed by thiolmethyltransferase, was not impaired in the SLE patients. There is a biochemical difference in sulphur metabolism between SLE and rheumatoid arthritis, since both pathways are impaired in the latter disorder.

Title
Increased prevalence of poor sulphoxidation in patients with rheumatoid arthritis: effect of changes in the acute phase response and second line drug treatment.

Author
Emery P; Bradley H; Gough A; Arthur V; Jubb R; Waring R

Source
Ann Rheum Dis, 1992 Mar, 51:3, 318-20

Abstract
A minority of normal subjects have an impaired ability to oxidise sulphur, which is associated with an increased risk of side effects when they receive sulphur containing drugs. In 114 patients with rheumatoid arthritis a greatly increased prevalence of poor sulphoxidation was found in 82 (72%) patients compared with 70/200 (35%) healthy controls, 45/121 (37%) controls matched for age, and 4/35 (11%) of the normal aged general population. In a longitudinal study of 37 patients there was no significant alteration in sulphoxidation status after the introduction of a second line drug or with marked changes in the acute phase response. It seems, therefore, that the poor sulphoxidation status in patients with RA is not an epiphenomenon and may be an important factor in determining the clinical features of rheumatoid disease.

Title
Genetic factors influencing the outcome of early arthritis--the role of sulphoxidation status

Author
Emery P; Bradley H; Arthur V; Tunn E; Waring R

Source
Br J Rheumatol, 1992 Jul, 31:7, 449-51

Abstract
A minority of individuals have an impaired ability to oxidize sulphur. An increased prevalence of this poor S-oxidation capacity has been observed in patients with established rheumatoid arthritis (RA). The role of this enzyme system in the development of disease was studied by testing the S-oxidation capacity of 54 patients with recent onset symmetrical poly-arthritis, who were followed up at 1 and 4 years. Those patients with persistent disease at 1 year had a prevalence of poor S-oxidation of 69%. At 4 years 74% of those with a diagnosis of RA were poor S-oxidizers compared to 31% of those who were asymptomatic (P less than 0.01). A defective ability to oxidize sulphur appears to predispose to persistent clinical disease.

Title
Structural organization and tissue-specific expression of the gene encoding rat cysteine dioxygenase.

Author
Tsuboyama N; Hosokawa Y; Totani M; Oka J; Matsumoto A; Koide T; Kodama H

Address
Department of Chemistry, Kochi Medical School, Japan.

Source

Gene, 1996 Nov, 181:1-2, 161-5

Abstract
Cysteine dioxygenase (CDO) is a key enzyme involved in the metabolism of L-cysteine. Genomic clones containing the 5'-flanking sequence of the rat CDO gene were isolated and characterized. The CDO gene spanned about 15 kb, and comprised 5 exons. All boundaries between the exons and introns matched the GT/AG rule. The major transcription start point (tsp) was A at 213 bp upstream from the ATG codon. The 5'-flanking region contained a TATA-box-like sequence and putative cis-acting regulatory elements. The 3' end of CDO was polyadenylated at several sites. Northern blots of RNA from rat tissues revealed the highest CDO mRNA level in the liver. Significant levels were observed in the kidney, lung and brain, implying tissue-specific differences in CDO promoter function.

Title
Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus.

Author
Perry TL; Norman MG; Yong VW; Whiting S; Crichton JU; Hansen S; Kish SJ

Source
Ann Neurol, 1985 Oct, 18:4, 482-9

Abstract
We describe neurochemical abnormalities found in the brains of 2 patients with autopsy-confirmed Hallervorden-Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. gamma-Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden-Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden-Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.

Title
Metabolism of L-cysteine in guinea pig liver.

Author
Hosaki Y; Nishina H; Ubuka T

Source
Acta Med Okayama, 1986 Feb, 40:1, 11-5

Abstract
The metabolism of L-cysteine in guinea pig liver was studied. Guinea pig liver contained 0.45 +/- 0.05 (mean +/- SD) mumol of cysteine, 0.180 +/- 0.080 mumol of 3-mercaptolactate-cysteine disulfide [S-(2-hydroxy-2-carboxyethylthio)cysteine, HCETC], and 8.082 +/- 0.516 mumol of reduced glutathione per g of fresh tissue. The taurine content was 0.912 +/- 0.158 mumol per g of fresh liver. Cysteine dioxygenase (EC 1.13.11.20) activity was several-fold lower than cysteine aminotransferase (EC 2.6.1.3) activity. Lactate dehydrogenase (EC 1.1.1.27) activity was about 10-fold higher than 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2) activity. These results indicate that the oxidative metabolism of L-cysteine in the guinea pig liver is not as active as in the rat liver and that L-cysteine, at least in part, is metabolized via the transaminative pathway, in which 3-mercaptopyruvate is partly reduced to 3-mercaptolactate and is utilized to form HCETC.

Title
Metabolism of cysteine, cysteinesulfinate and cysteinesulfonate in rats fed adequate and excess levels of sulfur-containing amino acids.

Author
Stipanuk MH; Rotter MA Address

Source
J Nutr, 1984 Aug, 114:8, 1426-37

Abstract
The oxidation of cysteine, cysteinesulfinate and cysteinesulfonate labeled with 14C in the 1- and 3-positions was studied in rats that had been fed diets with adequate or excess cysteine. Consumption of excess cysteine for 5 or 10 days resulted in an increase in hepatic cysteine dioxygenase activity and a decrease in hepatic cysteinesulfinate decarboxylase activity but had no effect on the oxidation of the C-1 or C-3 of cysteine, cysteinesulfinate or cysteinesulfonate. When the labeled compounds were administered by intraperitoneal injection, 41% of cysteine, 100% of cysteinesulfinate and 37% of cysteinesulfonate were oxidized over an 8-hour period. The percentage of the oxidized cysteine, cysteinesulfinate and cysteinesulfonate that was converted to taurine was calculated to be 83, 70 and 100%, respectively. When these same compounds were administered intragastrically, the relative flux to taurine was lower for all compounds; 41% of the oxidized cysteine, none of the cysteinesulfinate and 11% of the oxidized cysteinesulfonate appeared to be converted to taurine. Metabolism of intragastrically administered cysteine may be more indicative of what happens to dietary cysteine, whereas metabolism of intraperitoneally administered cysteine and cysteinesulfinate may be more indicative of liver metabolism and of the metabolism of endogenous cysteine and cysteinesulfinate.

Title
Pathways of cysteine metabolism in MND/ALS.

Author
Pean A; Steventon GB; Waring RH; Foster H; Sturman S; Williams AC Address School of Biochemistry, University of Birmingham, Edgbaston, UK.

Source
J Neurol Sci, 1994 Jul, 124 Suppl:, 59-61

Abstract
Analysis of plasma from MND/ALS patients has shown no significant differences in metabolism of cysteine derivatives, although a sub-set of the population has raised glutamate values. Cysteine dioxygenase was found to have reduced activity in vitro, consistent with previous findings of a high plasma cysteine/sulphate ratio.

Title
Expression and localization of cysteine dioxygenase mRNA in the liver, lung, and kidney of the rat.

Author
Shimada M; Koide T; Kuroda E; Tsuboyama N; Hosokawa Y; Watanabe M Address Department of Anatomy, Osaka Medical College, Japan.

Source
Amino Acids, 1998, 15:1-2, 143-50

Abstract
The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied by in situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions. Title Liver enzyme abnormalities in Parkinson's disease. Author Tanner CM Address Clinical Center for Parkinson's Disease and Movement Disorders, San Jose, California. Source Geriatrics, 1991 Aug, 46 Suppl 1:, 60-3 Abstract If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies.

Title
Abnormal liver enzyme-mediated metabolism in Parkinson's disease: a second look.

Author
Tanner CM Address Clinical Center for Parkinson's Disease and Movement Disorders, San Jose, CA 95128.

Source
Neurology, 1991 May, 41:5 Suppl 2, 89-91; discussion 92

Abstract
If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies.

Title
The genetic origin of responses to drugs.

Author
Waring RH; Emery P Address School of Biochemistry, University of Birmingham, UK.

Source
Br Med Bull, 1995 Apr, 51:2, 449-61

Abstract
Individual variation in drug metabolism has been extensively investigated. Population studies have shown that there is a wide range in metabolising ability for all detoxification pathways; the distributions may be unimodal (Gaussian) or polymodal, with subsets of individuals who differ from the majority. These may be poor metabolisers (PM) or extensive metabolisers (EM). In many cases, these phenotypes can be linked with the genotype. Frequently the PM phenotype is more susceptible to drug toxicity, while the EM phenotype requires increased dosage for therapeutic benefit. In some cases, phenotypes or genotypes appear to have increased susceptibility to clinical disease. These ideas are discussed for the cytochrome P-450 isozymes, FMO system, cysteine dioxygenase-linked oxidations, glucuronidation, sulphation, acetylation, glutathione conjugation and methylation pathways.

Title
Plasma cysteine, cystine, and glutathione in cirrhosis.

Author
Chawla RK; Lewis FW; Kutner MH; Bate DM; Roy RG; Rudman D

Source
Gastroenterology, 1984 Oct, 87:4, 770-6

Abstract

Plasma contains three forms of cyst(e)ine: cysteine, cystine, and protein-bound cysteine. The former is a thiol and the latter two are disulfides. The levels of all three types of cyst(e)ine, as well as the cysteinyl tripeptide glutathione, were measured in the plasma of 14 normal and 10 cirrhotic individuals. All subjects ate mixed foods. Some cirrhotic patients were studied during nasogastric hyperalimentation with Vivonex (Norwich Eaton Pharmaceuticals, Norwich, N.Y.) as well as during total parenteral nutrition with FreAmine III (American McGaw, Irvine, Calif.); neither formula contains cyst(e)ine. Regardless of the nature of the diet, cirrhotic patients had significantly subnormal values for cysteine, glutathione, and albumin. In addition, the following significant changes were found to be diet-dependent: (a) elevated methionine during Vivonex, (b) subnormal taurine during mixed foods and total parenteral nutrition, (c) depressed protein-bound cysteine during total parenteral nutrition, (d) depressed cyst(e)ine thiol/disulfide ratio during mixed foods, and (e) depressed total thiol during Vivonex and total parenteral nutrition. The data indicate multiple abnormalities in sulfur metabolism in cirrhosis.

Title
Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine.

Author
Ookhtens M; Kaplowitz N

Address
Department of Medicine, School of Medicine, University of Southern California, Los Angeles 90033, USA.

Source
Semin Liver Dis, 1998, 18:4, 313-29

Abstract
The most widely recognized function of reduced glutathione (GSH) is its defense against toxic compounds, whether exogenous, such as electophilic xenobiotics, or endogenous, such as reactive oxygen species, generated during normal oxidative metabolism and/or stress. However another no less significant role of GSH-namely its function as a reservoir and vehicle for packaging and transport of cyst(e)ine-has been receiving increasing attention. Because GSH is relatively more auto-oxidation resistant and stable than cyst(e)ine (CYSH), it serves as the preferred form for storage and transport of the latter especially in the extracellular and relatively much less reduced (than intracellular) milieu, where CYSH oxidizes to cystine (CYSS) rapidly. Over the past two decades, significant work has been going on to delineate the intra- and extrahepatic (interorgan) turnover, transport, and disposal of GSH and define the quantitative role of these processes in interorgan homeostasis of GSH, CYSH, and CYSS. These studies have identified the liver as the central organ of interorgan GSH homeostasis, with sinusoidal GSH efflux as the major determinant of plasma GSH, CYSH, CYSS, and thiol-disulfide status of plasma. This article focuses on the principal components and determinants of interorgan homeostasis of GSH and its breakdown products. It also presents the current state of knowledge under both normal and diseased states.

Title
Distribution of oxidized and reduced forms of glutathione and cysteine in rat plasma.

Author Lash LH; Jones DP

Source
Arch Biochem Biophys, 1985 Aug, 240:2, 583-92

Abstract
The distribution of the glutathionyl moiety between reduced and oxidized forms in rat plasma was markedly different than that for the cysteinyl moiety. Most of the glutathionyl moiety was present as mixed disulfides with cysteine and protein whereas most of the cysteinyl moiety was present as cystine. Seventy percent of total glutathione equivalents was bound to proteins in disulfide linkage. The distribution of glutathione equivalents in the acid-soluble fraction was 28.0% as glutathione, 9.5% as glutathione disulfide, and 62.6% as the mixed disulfide with the cysteinyl moiety. In contrast, 23% of total cysteine equivalents was protein-bound. The distribution of cysteine equivalents in the acid-soluble fraction was 5.9% as cysteine, 83.1% as cystine, and 10.8% as the mixed disulfide with the glutathionyl moiety. A first-order decline in glutathione occurred upon in vitro incubation of plasma and was due to increased formation of mixed disulfides of glutathione with cysteine and protein. This indicates that plasma thiols and disulfides are not at equilibrium, but are in a steady-state maintained in part by transport of these compounds between tissues during the inter-organ phase of their metabolism. The large amounts of protein-bound glutathione and cysteine provide substantial buffering which must be considered in analysis of transient changes in glutathione and cysteine. In addition, this buffering may protect against transient thiol-disulfide redox changes which could affect the structure and activity of plasma and plasma membrane proteins.

Title
Oxygen activating nonheme iron enzymes.

Author
Lange SJ; Que L Jr

Address
Department of Chemistry Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, USA.

Source
Curr Opin Chem Biol, 1998 Apr, 2:2, 159-72

Abstract
The past year has witnessed significant advances in the study of oxygen-activating nonheme iron enzymes. Thirteen crystal structures of substrate and substrate analog complexes of protocatechuate 3, 4-dioxygenase have revealed intimate details about changes at the enzyme active site during catalysis. Crystallographic data have established a 2-His-1-carboxylate facial triad as a structural motif common to a number of mononuclear nonheme iron enzymes, including isopenicillin N synthase, tyrosine hydroxylase and naphthalene dioxygenase. The first metrical data has been obtained for the high valent intermediates Q and X of methane monooxygenase and ribonucleotide reductase, respectively. The number of enzymes thought to have nonheme diiron sites has been expanded to include alkene monooxygenase from Xanthobacter strain Py2 and the membrane bound alkane hydroxylase from Pseudomonas oleovorans (AlkB). Finally, synthetic complexes have successfully mimicked chemistry performed by both mono- and dinuclear nonheme iron enzymes, such as the extradiol-cleaving catechol dioxygenases, lipoxygenase, alkane and alkene monoxygenases and fatty acid desaturases.

Title
Evidence of histidine coordination to the catalytic ferrous ion in the ring-cleaving 2,2',3-trihydroxybiphenyl dioxygenase from the dibenzofuran-degrading bacterium Sphingomonas sp. strain RW1.

Author
Bertini I; Capozzi F; Dikiy A; Happe B; Luchinat C; Timmis KN

Address
Department of Chemistry, University of Florence, Italy.

Source
Biochem Biophys Res Commun, 1995 Oct, 215:3, 855-60

Abstract
The 1H NMR spectra of an aromatic ring-cleaving extradiol dioxygenase, 2,2',3-trihydroxybiphenyl dioxygenase of the dibenzofuran-degrading bacterium Sphingomonas sp. strain RW1, are reported. In the catalytically active reduced form of the monomeric enzyme (MW = 32 kDa), three broad strongly downfield shifted signals were observed, two of which disappeared in D2O solution. Their shifts and linewidths are consistent with ring NH and meta-like protons of coordinated histidines. These signals show strong sensitivity to the presence of the substrate. The oxidized form of the enzyme shows no hyperfine shifted signals. It is suggested that the high spin Fe(II) ion present in the active form of the enzyme is coordinated by at least two histidines. This is the first report of hyperfine shifted NMR signals being detected for an extradiol dioxygenase.

Title
Purification and characterization of a cysteine dioxygenase from the yeast phase of Histoplasma capsulatum.

Author
Kumar V; Maresca B; Sacco M; Goewert R; Kobayashi GS; Medoff G

Source
Biochemistry, 1983 Feb, 22:4, 762-8

Abstract
A cysteine dioxygenase, cysteine oxidase (EC 1.13.11.20), has been purified from the cytosolic fraction of yeast phase cells of the dimorphic fungus Histoplasma capsulatum. The cysteine oxidase is an iron-containing dioxygenase with a molecular weight of 10500 (+/- 1500) and is present only in the yeast phase of the fungus. The enzyme is highly specific for L-cysteine, with a Km of 2 X 10(-5) M in vitro. The product of cysteine oxidation is cysteinesulfinic acid, as analyzed by thin-layer chromatography and mass spectroscopy. To our knowledge, this is the first cysteine oxidase isolated from a fungus, and it probably plays an important role in the mycelial to yeast phase transition of H. capsulatum during which redox potential and cysteine levels are crucial factors.

 

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