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Methionine

Here are scientific studies relating to the amino acid methionine, and its cousin, S-adenosyl-L-methionine.

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HealthGate Documents

Record 1 from database: MEDLINE
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Title

The biochemistry of endogenous organosulphur compounds.

Author

James SP

Address

School of Biochemistry, University of Birmingham, UK.

Source

Drug Metabol Drug Interact, 1988, 6:3-4, 167-82

Abstract

The role and metabolism of methionine and cysteine in mammals are described. An outline of the history of glutathione, of its function in maintaining the thiol status of the cell and of its protective action against oxidative stress, is given. The importance of glutathione reductase, glutathione peroxidases, glutathione-S-transferases in endogenous metabolism and of gamma-glutamyltranspeptidase is described. The relationship between cysteine and glutathione is considered together with the inter-organ translocation of glutathione and its metabolism.

Language of Publication

English

Unique Identifier

90151143

MeSH Heading (Major)

Cysteine|*ME; Glutathione|*ME; Methionine|*ME; Sulfur|*ME

MeSH Heading

Animal; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0792-5077

Country of Publication

ENGLAND

CAS Registry/EC Number

4371-52-2 (Cysteine); 70-18-8 (Glutathione); 7005-18-7 (Methionine); 7704-34-9 (Sulfur)

Record 2 from database: MEDLINE
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Title

Methioninase: a therapeutic for diseases related to altered methionine metabolism and transmethylation: cancer, heart disease, obesity, aging, and Parkinson's disease.

Author

Hoffman RM

Address

AntiCancer, Incorporated, San Diego, CA 92111, USA. all@anticancer.com

Source

Hum Cell, 1997 Mar, 10:1, 69-80

Abstract

Methionine metabolism and transmethylation are central to the metabolism and differentiation of all known cells. In enkaryotic organisms, methionine metabolism and transmethylation are of paramount importance in modification and regulation of proteins, lipids, and nucleic acids. The differential methylation of genes regulates their expression in the myriad of cells in eukaryotic organisms. Disruption and abnormalities in methionine metabolism and transmethylation seems to be associated with the major diseases of mankind, including cancer, heart disease, aging, obesity, and Parkinson's disease. In this review, we describe how aberrant and abnormal methionine metabolism and transmethylation are related to these major diseases. Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases.

Language of Publication

English

Unique Identifier

97378448

MeSH Heading (Major)

Aging|*/ME; Heart Diseases|*ET; Methionine|*ME; Neoplasms|DT/*ET/ME; Obesity|*ET; Parkinson Disease|*ET; Sulfhydrases|PD/*TU

MeSH Heading

Animal; Drug Interactions; Drug Therapy, Combination; Human; Methylation; Recombinant Proteins|PD/TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0914-7470

Country of Publication

JAPAN

CAS Registry/EC Number

EC 4.4. (Sulfhydrases); EC 4.4.1.11 (L-methionine gamma-lyase); 0 (Recombinant Proteins); 7005-18-7 (Methionine)

Record 3 from database: MEDLINE
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Title

Methionine metabolism: a window on carcinogenesis?

Author

Gatton-Umphress TL; Weber KA; Seidler NW

Address

University of Health Sciences, Kansas City, Mo.

Source

Hosp Pract (Off Ed), 1993 Sep 30, 28:9A, 83-5, 89-90

Abstract

Recent experimental evidence links changes in methionine metabolism to the onset and progression of cancer. Aberrant methylation reactions and polyamine synthesis may alter genome stability, gene expression, and cell proliferation.

Language of Publication

English

Unique Identifier

94013160

MeSH Heading (Major)

Methionine|*ME; Neoplasms|DI/*ET/ME

MeSH Heading

Cell Transformation, Neoplastic|ME; DNA Damage; DNA Repair; Human; Oncogene Proteins|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

8750-2836

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Oncogene Proteins); 7005-18-7 (Methionine)

Record 4 from database: MEDLINE
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Title

Methionine sulfoxide and the oxidative regulation of plasma proteinase inhibitors.

Author

Swaim MW; Pizzo SV

Address

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.

Source

J Leukoc Biol, 1988 Apr, 43:4, 365-79

Abstract

The sensitivity of methionine residues to oxidation is a mechanism by which many proteins, including plasma proteinase inhibitors, may be oxidatively inactivated. Much evidence suggests that methionine oxidation and concurrent losses of protein activity not only occur widely in living systems but are physiologic, homeostatic processes. Neutrophils, macrophages and other leukocytes secrete large quantities of powerful oxidants at sites of inflammation and may readily bring about methionine oxidative inactivation of proteins. In particular, oxidation of proteinase inhibitors may favorably alter the proteinase-antiproteinase balance to facilitate tissue remodeling and protection from invading organisms. Leukocyte-mediated inhibitor oxidation also appears to regulate local immunosuppressive activity. Pathophysiologic processes such as emphysema and rheumatoidal disease involve derangements of these homeostatic mechanisms.

Language of Publication

English

Unique Identifier

88171127

MeSH Heading (Major)

Methionine|*AA/ME; Peptide Peptidohydrolases|*BL; Protease Inhibitors|*BL

MeSH Heading

alpha 1-Antitrypsin|BL; alpha-Macroglobulins|ME; Animal; Binding Sites; Human; Leukocytes|EN; Oxidation-Reduction; Smoke; Trypsin Inhibitors|BL/ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0741-5400

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.4.- (Peptide Peptidohydrolases); 0 (alpha 1-Antitrypsin); 0 (alpha-Macroglobulins); 0 (Protease Inhibitors); 0 (Trypsin Inhibitors); 454-41-1 (methionine sulfoxide); 7005-18-7 (Methionine)

Record 5 from database: MEDLINE
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Title

PET for diagnosis of malignant lymphoma of the scalp: comparison of [11C]methyl-L-methionine and [18F]fluoro-2-deoxygluc ose.

Author

Tsuyuguchi N; Hakuba A; Okamura T; Ochi H; Suzuki T; Sunada I

Address

Department of Neurosurgery, Osaka City University Medical School, Japan.

Source

J Comput Assist Tomogr, 1997 Jul-Aug, 21:4, 590-3

Abstract

A 43-year-old woman was admitted with a tumor mass in her forehead. Two months previously, a lump in her breast had been diagnosed as mastopathy. Palpation revealed an elastically hard immobile tumor mass in her forehead. MRI detected a tumoral lesion of generally uniform contrast involving frontal subcutaneous, cranial, and intracranial regions. PET demonstrated more intensive and wider accumulation of [11C]methyl-L-methionine (Met) than of [18F]fluoro-2-deoxyglucose (FDG). Biopsy of the forehead mass was performed, which was diagnosed as B-cell-type malignant lymphoma. The tumor mass in the forehead then shrank spontaneously, as confirmed by palpation and MRI. The tumor mass in the left breast was totally extirpated and histologically diagnosed as B-cell-type malignant lymphoma, like the tumor mass in the forehead. Postoperatively, chemotherapy (VEPA) was performed. Although FDG accumulation had not been detected, postchemotherapy PET demonstrated slight Met accumulation, suggesting the presence of a residual tumor. PET served well to detect the lesion and evaluate therapeutic efficacy in malignant lymphoma. Met-PET was more sensitive to malignant lymphoma than FDG-PET.

Language of Publication

English

Unique Identifier

97359847

MeSH Heading (Major)

Carbon Radioisotopes|*DU; Deoxyglucose|*AA/DU; Fluorine Radioisotopes|*DU; Lymphoma|*RI/TH; Methionine|*AA/DU; Scalp|PA/RA/*RI; Skin Neoplasms|*RI/TH; Tomography, Emission-Computed|*MT

MeSH Heading

Adult; Case Report; Combined Modality Therapy; Comparative Study; Female; Human; Magnetic Resonance Imaging; Tomography, X-Ray Computed

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

ISSN

0363-8715

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Carbon Radioisotopes); 0 (Fluorine Radioisotopes); 10332-17-9 (methionine methyl ester); 154-17-6 (Deoxyglucose); 29702-43-0 (fludeoxyglucose F 18); 7005-18-7 (Methionine)

Record 6 from database: MEDLINE
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Title

Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity.

Author

Watkins D; Rosenblatt DS

Address

Centre for Human Genetics, McGill University, Montreal, Quebec, Canada.

Source

Am J Med Genet, 1989 Nov, 34:3, 427-34

Abstract

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.

Language of Publication

English

Unique Identifier

90086914

MeSH Heading (Major)

Homocystinuria|*EN/GE; Methionine|BL/*DF; Methyltransferases|*DF; Tetrahydropteroylglutamate Methyltransferase|*DF/GE; Vitamin B 12|*AA/BL/TU

MeSH Heading

Adult; Anemia, Megaloblastic|ET; Cells, Cultured; Female; Fibroblasts|EN; Genetic Complementation Test; Human; Infant; Infant, Newborn; Male; Nervous System Diseases|ET; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0148-7299

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 2.1.1. (Methyltransferases); EC 2.1.1.13 (Tetrahydropteroylglutamate Methyltransferase); 13422-55-4 (mecobalamin); 68-19-9 (Vitamin B 12); 7005-18-7 (Methionine)

Record 7 from database: MEDLINE
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Title

Plasma homocysteine and methionine tolerance in early-onset vascular disease.

Author

Brattström L; Israelsson B; Hultberg B

Address

Department of Neurology, University Hospital, Lund, Sweden.

Source

Haemostasis, 1989, 19 Suppl 1:, 35-44

Abstract

In three different studies we tested the hypothesis that early-onset vascular disease is associated with impaired homocysteine metabolism which could contribute to the development of arteriosclerosis and thrombosis. In patients with occlusive vascular disease before the age of 60, a post-methionine load increase of plasma homocysteine exceeding the highest value for comparable healthy control subjects was found in 1 of 21 with myocardial infarction (5%), 14 of 37 with aorto-iliac disease (38%), and 17 of 53 with cerebrovascular disease (32%). This might indicate heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency. Concentrations of serum vitamin B12 and red cell folate had an important modulating effect on plasma homocysteine concentrations in the fasting state.

Language of Publication

English

Unique Identifier

90034427

MeSH Heading (Major)

Homocysteine|*BL; Methionine|*PK; Vascular Diseases|*BL

MeSH Heading

Drug Tolerance; Human; Risk Factors

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0301-0147

Country of Publication

SWITZERLAND

CAS Registry/EC Number

454-28-4 (Homocysteine); 7005-18-7 (Methionine)

Record 8 from database: MEDLINE
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Title

The influence of ethanol on hepatic transmethylation.

Author

Barak AJ; Beckenhauer HC

Address

Liver Study Unit, Veterans Administration Medical Center, Omaha, NE 68105.

Source

Alcohol Alcohol, 1988, 23:1, 73-7

Abstract

One of the most important biochemical pathways in the organism is the biosynthesis of methionine from the methylation of homocysteine. Two different reactions are responsible for this methylation, one utilizing N5-methyltetra-hydrofolate as a methylating agent and the other using betaine as the methyl donor. This paper reviews some recent findings in this laboratory, which demonstrate that ethanol-feeding to rats impairs the folate-induced reaction. Our findings also show that this impairment is compensated for through the adaptive increase in the enzyme using betaine in the biosynthesis of methionine. Further studies indicate that the mechanism of action in the impairment may occur through the formation of individual adducts between the folate-induced enzyme (methionine synthetase), its essential cofactors and acetaldehyde, a metabolic product of ethanol. These findings suggest a basis for why rats are more resistant to alcoholic liver injury than humans and may offer a means of protecting against alcoholic liver injury in man.

Language of Publication

English

Unique Identifier

88192777

MeSH Heading (Major)

Alcohol, Ethyl|*PD; Liver|*DE; Methionine|*ME

MeSH Heading

Animal; Human; Rats; S-Adenosylmethionine|ME; Tetrahydropteroylglutamate Methyltransferase|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0735-0414

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 2.1.1.13 (Tetrahydropteroylglutamate Methyltransferase); 29908-03-0 (S-Adenosylmethionine); 64-17-5 (Alcohol, Ethyl); 7005-18-7 (Methionine)

Record 9 from database: MEDLINE
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Title

Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease?

Author

Regland B; Gottfries CG

Address

Department of Geriatrics and Rehabilitation, Uddevalla Hospital, Rosenhäll, Sweden.

Source

Med Hypotheses, 1992 May, 38:1, 11-9

Abstract

This is a presentation of the hypothesis of a pathogenetic mechanism common to the dementia seen in Alzheimer's disease (AD), Down's Syndrome (DS) and the acquired immunodeficiency syndrome (AIDS). As there is experimental evidence of defective DNA repair capacity in AD and DS, unrepaired damage to DNA occurs in these diseases and may lead to complete breakdown of cellular function and ultimate cell death. Cobalamin and folate are coordinated in a vulnerable key position in the synthesis of DNA and S-adenosylmethionine (SAM). Cobalamin/folate deficiency, a significant feature in senile dementia of Alzheimer type and in AIDS-related dementia complex, will result in concomitant slowed synthesis of DNA and SAM. The enzyme cystathionine-beta-synthetase (CBS) has been localized to the chromosome band 21q22.3. Owing to gene dosage, CBS activity is increased in trisomy 21. As a consequence, cobalamin/folate metabolism is inhibited, which leads to slowing of DNA and SAM synthesis in DS patients. Amyloidosis is a hallmark of AD and DS brain neuropathology and recent experimental findings support the view that amyloid or amyloid precursors stimulate DNA synthesis, which is in agreement with the hypothesis presented in this paper. In summary, demented patients with cobalamin/folate deficiency, trisomy 21 and human immunodeficiency virus (HIV) infection display a simultaneous downregulation of DNA and SAM synthesis, which may indicate a pathway common to the dementia seen in AD, DS and AIDS.

Language of Publication

English

Unique Identifier

92310301

MeSH Heading (Major)

Alzheimer's Disease|PA/*PP; AIDS Dementia Complex|PA/*PP; Dementia|ET/PA/*PP; Down Syndrome|PA/*PP; DNA|*BI; Methionine|*BI

MeSH Heading

Amyloidosis|ET/PA/PP; Cell Death; DNA Repair; DNA Replication; Human; Models, Biological

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0306-9877

Country of Publication

ENGLAND

CAS Registry/EC Number

7005-18-7 (Methionine); 9007-49-2 (DNA)

Record 10 from database: MEDLINE
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Title

Methionine deprivation regulates the translation of functionally-distinct c-Myc proteins.

Author

Hann SR

Address

Department of Cell Biology, Vanderbilt Univeristy, School of Medicine, Nashville, Tennessee 37232-2175, USA.

Source

Adv Exp Med Biol, 1995, 375:, 107-16

Abstract

Numerous studies have demonstrated a critical role for the c-myc gene in the control of cellular growth. Alterations of the c-myc gene have been found associated with many different types of tumors in several species, including humans. The increased synthesis of one of the major forms of c-Myc protein, c-Myc 1, upon methionine deprivation provides a link between the regulation of oncogenes and the nutritional status of the cell. While deregulation or overexpression of the other major form, c-Myc 2, has been shown to cause tumorigenesis, the synthesis of c-Myc 1 protein is lost in many tumors. This suggests that the c-Myc 1 protein is necessary to keep the c-Myc 2 protein "in check" and prevent certain cells from becoming tumorigenic. Indeed, we have shown that overproduction of c-Myc 1 can inhibit cell growth. We have also shown that c-Myc 1 and 2 proteins have a differential molecular function in the regulation of transcription through a new binding site of Myc/Max heterodimers. We have also recently identified new translational forms of the c-Myc protein which we term delta-c-Myc. These proteins arise from translational initiation at downstream start sites which yield N-terminally-truncated c-Myc proteins. Since these proteins lack a significant portion of the transactivation domain of c-Myc, they behave as dominant-negative inhibitors of the full-length c-Myc 1 and 2 proteins. The synthesis of delta-c-Myc proteins is also regulated during cell growth and is repressed by methionine deprivation. Therefore, the synthesis of c-Myc 1 and delta-c-Myc proteins are reciprocally regulated by methionine availability. We have also found some tumor cell lines which synthesize high levels of the delta-c-Myc proteins. Taken together, our data suggest that c-Myc function is dependent on the levels of these different translational forms of c-Myc protein which are regulated by the nutritional status of the cell during growth. Numerous reports have demonstrated a fundamental and diverse role for the myc gene in cellular events, including proliferation, differentiation and apoptosis (Cole 1986; Spencer and Groudine 1991; Askew et al. 1991; Evan et al. 1992). This is dramatically illustrated by the frequent occurrence of a variety of tumors in many species having alterations of myc genes and the transduction of c-myc sequences by retroviruses (Spencer and Groudine 1991).4+ Eisenman 1990).(ABSTRACT TRUNCATED AT 400 WORDS)

Language of Publication

English

Unique Identifier

95373361

MeSH Heading (Major)

Methionine|AD/*DF; Proto-Oncogene Proteins c-myc|*GE/PH; Translation, Genetic|*

MeSH Heading

Animal; Base Sequence; Gene Expression Regulation; Genes, myc; Human; Molecular Sequence Data; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-2598

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Proto-Oncogene Proteins c-myc); 7005-18-7 (Methionine)

Record 11 from database: MEDLINE
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Title

S-adenosyl-L-methionine synthetase and methionine metabolism deficiencies in cirrhosis.

Author

Mato JM; Alvarez L; Ortiz P; Mingorance J; Durán C; Pajares MA

Address

Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.

Source

Adv Exp Med Biol, 1994, 368:, 113-7

Abstract

Methionine metabolism impairment in human liver disease has been related with an alteration in SAM-synthetase. This deficiency is produced by a post-translational event since human liver cirrhosis presents normal levels of SAM-synthetase mRNA in spite of a more than 50% diminution in its activity. A series of different experiments on the structure and activity of this enzyme have provided strong evidence that SAM-synthetase is regulated by reduced/oxidized glutathione ratio. Restoration of glutathione levels by the addition of S-adenosyl-methionine or glutathione esters in various experimental conditions (buthionine sulfoximine and carbon tetrachloride intoxication) resulted in a normalization of the SAM-synthetase diminution caused by the toxics and an attenuation of the morfological alteration produced in the liver, including fiber production. This findings might have pharmacological implications in the treatment of liver diseases, since the possible beneficial effect of long term administration of SAM could include a reduction of fiber production.

Language of Publication

English

Unique Identifier

95259561

MeSH Heading (Major)

Liver Cirrhosis|DT/EN/*ME/PA; Methionine|*DF/ME; Methionine Adenosyltransferase|*DF

MeSH Heading

Animal; Human; Liver Cirrhosis, Experimental|DT/EN/ME/PA; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-2598

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 2.5.1.6 (Methionine Adenosyltransferase); 7005-18-7 (Methionine)

Record 12 from database: MEDLINE
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Title

Oxidation of methionyl residues in proteins: tools, targets, and reversal.

Author

Vogt W

Address

Max Planck Institut für experimentelle Medizin, Göttingen, Germany.

Source

Free Radic Biol Med, 1995 Jan, 18:1, 93-105

Abstract

Methionine (Met) is one of the most readily oxidized amino acid constituents of proteins. It is attacked by H2O2, hydroxyl radicals, hypochlorite, chloramines, and peroxynitrite, all these oxidants being produced in biological systems. The oxidation product, Met sulfoxide, can be reduced back to Met by Met sulfoxide reductase. Numerous proteins lose functional activity by Met oxidation. However, functional activation of proteins by Met oxidation has also been observed. Functional changes by Met oxidation in a given protein appear to have pathophysiological significance in some cases. Considering the reversibility of Met oxidation and the functional changes associated with the oxidation, it seems possible that Met oxidation/reduction in proteins may be one means to control homeostasis in biological systems.

Language of Publication

English

Unique Identifier

95203764

MeSH Heading (Major)

Methionine|AA/*CH/ME; Proteins|*CH

MeSH Heading

alpha 1-Antitrypsin|CH; Complement 5|CH; Free Radicals; Hormones|CH; Human; Oxidation-Reduction; Oxidoreductases|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0891-5849

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1. (Oxidoreductases); EC 1.- (methionine sulfoxide reductase); 0 (alpha 1-Antitrypsin); 0 (Complement 5); 0 (Free Radicals); 0 (Hormones); 0 (Proteins); 454-41-1 (methionine sulfoxide); 7005-18-7 (Methionine)

Record 13 from database: MEDLINE
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Title

Methyl donors in the diet and responses to chemical carcinogens.

Author

Rogers AE

Address

Boston University School of Medicine, Department of Pathology and Laboratory Medicine, Mallory Institute of Pathology, MA 02118.

Source

Am J Clin Nutr, 1995 Mar, 61:3 Suppl, 659S-665S

Abstract

Dietary deficiency of labile methyl donors (choline and methionine) increases spontaneous and chemically induced hepatocarcinogenesis in rats. Chemical carcinogenesis in the colon, mammary gland, esophagus, and pancreas also may be increased. The mechanism of the dietary effect is not known but may be related to reduced methylation of DNA and RNA, hyperplasia of target cells, increased peroxidative damage, and altered carcinogen or promoter metabolism. Folate deficiency also is associated with increased carcinogenesis, an effect that may be mediated through participation in methyl metabolism; this has been less extensively studied. Deficiency of these three nutrients also may play a role in the elevated cancer risk in humans that is associated with ethanol intake.

Language of Publication

English

Unique Identifier

95185441

MeSH Heading (Major)

Carcinogens|*TO; Choline Deficiency|*CO; Folic Acid Deficiency|*CO; Methionine|*DF; Neoplasms|*ET

MeSH Heading

Animal; Diet; Human; Liver Neoplasms, Experimental|ET; Methylation

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0002-9165

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Carcinogens); 7005-18-7 (Methionine)

Record 14 from database: MEDLINE
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Title

Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis.

Author

Pisi E; Marchesini G

Address

Istituto di Clinica Medica Generale e Terapia Medica, Università di Bologna, Italy.

Source

Drugs, 1990, 40 Suppl 3:, 65-72

Abstract

The liver is actively involved in the metabolism of the sulphur-containing essential amino acid, methionine. Methionine is transformed into S-adenosyl-L-methionine (SAMe) and then into sulphur-containing metabolites (cysteine, taurine and glutathione) via the trans-sulphuration pathway. Liver disease may affect the trans-sulphuration pathway and decrease the clearance of methionine, which leads to increased fasting methionine concentrations in blood and reduced formation of cysteine and glutathione. There is evidence that this defect, located at the level of SAMe-synthetase, may cause nutritional defects and contribute to negative nitrogen balance whenever non-essential sulphur-containing amino acids are not supplied in adequate amounts. In addition, cirrhotic patients may be at increased risk of hepatotoxicity after treatment with substances which are detoxified via glutathione. The SAMe-synthetase block may be overcome by administration of oral or intravenous SAMe, which improves the fasting amino acid profile and increases the hepatic glutathione concentration. Controlled studies on long term SAMe treatment in patients with cirrhosis are needed to confirm this possible beneficial effect.

Language of Publication

English

Unique Identifier

91184034

MeSH Heading (Major)

Liver Cirrhosis|DT/*ME; Methionine|*ME/PK

MeSH Heading

Amino Acids|BL; Human; S-Adenosylmethionine|TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amino Acids); 29908-03-0 (S-Adenosylmethionine); 7005-18-7 (Methionine)

Record 15 from database: MEDLINE
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Title

Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part I. Biochemical implications.

Author

Mato JM; Corrales F; Martin-Duce A; Ortiz P; Pajares MA; Cabrero C

Address

Departamento de Metabolismo, Nutrición y Hormonas, Fundación Jiménez Diaz, Madrid, Spain.

Source

Drugs, 1990, 40 Suppl 3:, 58-64

Abstract

The energy-dependent conversion of methionine to S-adenosyl-L-methionine (SAMe) is catalysed by S-adenosyl-L-methionine synthetase (SAMe-synthetase) in the liver. In the hepatocyte, an equilibrium exists between the high and low molecular weight forms of SAMe-synthetase, which consist of a tetramer and a dimer, respectively, of a 48.5 kilodalton subunit. The 2 enzymic forms differ in their affinity for methionine and sensitivity to inhibition by pyrophosphate; 2 of the sulfhydryl groups of SAMe-synthetase have been identified as essential for the normal functioning of the enzyme. In patients with liver cirrhosis, a marked reduction in the utilisation of the high molecular weight SAMe-synthetase and displacement of the equilibrium occur, the molecular mechanism of which has yet to be established. This loss of activity is associated with a delay in methionine clearance and impairment of the trans-sulphuration pathway, which normally eliminates excess methionine by oxidising homocysteine to sulphate anion. It is hypothesised that in normal liver function the essential sulfhydryl groups of SAMe-synthetase are protected from oxidation by glutathione, a by-product of the trans-sulphuration pathway. However, glutathione levels are reduced in liver cirrhosis, and this may result in increased oxidation of the essential sulfhydryl groups, and consequent inactivation of the enzyme. Thus, the trans-sulphuration pathway may play an important role in the maintenance of normal SAMe-synthetase activity.

Language of Publication

English

Unique Identifier

91184033

MeSH Heading (Major)

Liver|*ME/PH; Liver Diseases|*ME; Methionine|*ME; Methionine Adenosyltransferase|*BI/ME; S-Adenosylmethionine|*ME

MeSH Heading

Human; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 2.5.1.6 (Methionine Adenosyltransferase); 29908-03-0 (S-Adenosylmethionine); 7005-18-7 (Methionine)

Record 16 from database: MEDLINE
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Title

Chemoattractant receptor affinity reflects its ability to transduce different biological responses.

Author

Snyderman R

Source

Agents Actions Suppl, 1983, 12:, 323-36

Abstract

The oligopeptide chemotactic factor receptor in human PMN membranes exists in two affinity states which are in part interconvertible and regulated by guanine nucleotides. In whole cells, only one affinity of the receptor can be seen, presumably due to the high intracellular levels of guanine nucleotides as well as rapidly ongoing cellular processes which allow the detection of only a single affinity state. There is strong evidence to suggest that the affinity of the chemoattractant receptor in whole PMNs can be modified by agents which alter the physical state of the PMN membrane. The average affinity of the oligopeptide chemotactic factor receptor can be enhanced by aliphatic alcohols which decrease membrane microviscosity. Under these conditions, chemotactic responsiveness of PMNs is enhanced but 0(2-) production and secretion initiated by chemoattractants is markedly depressed. When the affinity of the receptor is lowered as in the case of amphotericin B, chemotaxis is depressed but lysozyme secretion is enhanced. These data indicate that the transduction mechanisms for certain biological responses initiated by the chemoattractant receptor are heterogeneous. It can be hypothesized that the particular transduction pathway initiated by chemoattractant receptor occupancy is reflected by the affinity state of the receptor. The higher affinity state initiates chemotactic signals whereas the lower affinity state initiates 0(2-) production and secretion. By altering the affinity of the receptor using pharmacological means one may be able to modify the biological activity of human PMNs.

Language of Publication

English

Unique Identifier

83175104

MeSH Heading (Major)

Methionine|*AA; N-Formylmethionine|*AA/ME; Neutrophils|*ME; Oligopeptides|*ME; Receptors, Cell Surface|DE/*ME

MeSH Heading

Alcohols|PD; Amphotericin B|PD; Animal; Comparative Study; Guanine Nucleotides|PD; Human; In Vitro; Kinetics; Lysosomes|DE/EN; Membrane Fluidity|DE

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0379-0363

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (chemotactic peptide receptor); 0 (Alcohols); 0 (Guanine Nucleotides); 0 (Oligopeptides); 0 (Receptors, Cell Surface); 1397-89-3 (Amphotericin B); 4289-98-9 (N-Formylmethionine); 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine); 7005-18-7 (Methionine)

Record 17 from database: MEDLINE
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Title

Dynamics of human neutrophil receptors for the chemoattractant fmet-leu-phe.

Author

Gallin JI; Seligmann BE; Fletcher MP

Source

Agents Actions Suppl, 1983, 12:, 290-308

Abstract

Neutrophils contain an intracellular pool of binding sites for the chemoattractant fmet-leu-phe with the same density as specific granules. This pool of receptors appears to be translocated to the plasma membrane during degranulation and may be important for receptor renewal during chemotaxis. Scatchard analyses of fmet-leu-phe binding to neutrophils and isolated plasma membranes are nonlinear and calculated Hill coefficients of binding to these fractions were about 0.67, suggesting negative cooperativity and/or heterogeneity of receptors. Some of the features of the nonlinear Scatchard curves may reflect heterogeneity of binding among cells since binding of fmet-leu-phe-lys-fluorescein to cells is heterogeneous when simultaneously monitored in the fluorescence activated cell sorter with a fluorescent probe of membrane potential. Following addition of a chemoattractant cells showing a depolarization have more chemoattractant associated with them than cells showing no change of membrane potential or a hyperpolarization. The cell associated chemoattractant is largely in a displaceable pool on the cells showing depolarization while it is in a nondisplaceable pool in the cells that either do not respond or show a hyperpolarization. Studies of the adaptation of human neutrophils responsiveness to fmet-leu-phe elicited membrane potential changes indicate that fmet-leu-phe stimulated decreases in receptor affinity accompany such adaptation. This decreased affinity appears to involve heterogeneity and/or negative cooperative interaction of receptors. The dynamics of chemoattractant receptors that have been reviewed provide further insights for studying the concepts behind the spatial and temporal mechanisms by which cells respond and adapt to a gradient of chemoattractant.

Language of Publication

English

Unique Identifier

83175102

MeSH Heading (Major)

Methionine|*AA; N-Formylmethionine|*AA/ME; Neutrophils|*PH; Oligopeptides|*ME; Receptors, Cell Surface|*ME

MeSH Heading

Adaptation, Physiological; Cell Membrane|PH; Chemotaxis, Leukocyte; Comparative Study; Cytoplasmic Granules|PH; Fluorescent Dyes; Human; In Vitro; Kinetics

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0379-0363

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (chemotactic peptide receptor); 0 (Fluorescent Dyes); 0 (Oligopeptides); 0 (Receptors, Cell Surface); 4289-98-9 (N-Formylmethionine); 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine); 7005-18-7 (Methionine)

Record 18 from database: MEDLINE
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Title

Biochemistry of sulfur-containing amino acids.

Author

Cooper AJ

Source

Annu Rev Biochem, 1983, 52:, 187-222

Abstract

The literature on sulfur amino acid metabolism is too vast for a short chapter to cover in great depth. I attempt here a brief overview with references to many specialized review articles. This review emphasizes aspects of sulfur amino acid metabolism elucidated in the last ten years, in particular aspects not generally covered in biochemistry texts, e.g. transaminative pathways of methionine metabolism. A selected list of reviews is given in references 1-15. References to reviews on glutathione are covered in the chapter by A. Meister in this volume (1a).

Language of Publication

English

Unique Identifier

83307233

MeSH Heading (Major)

Cysteine|*ME; Homocysteine|*ME; Methionine|AA/*ME; S-Adenosylmethionine|*ME

MeSH Heading

Adenosine|AA/ME; Amino Acid Metabolism, Inborn Errors|ME; Animal; Human; Oxidoreductases|ME; Structure-Activity Relationship; Sulfur|ME; Sulfurtransferases|ME; Support, U.S. Gov't, P.H.S.; Thionucleosides|ME; Thiosulfate Sulfurtransferase|ME

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0066-4154

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1. (Oxidoreductases); EC 1.8.- (thiosulfate reductase); EC 2.8.1 (Sulfurtransferases); EC 2.8.1.1 (Thiosulfate Sulfurtransferase); EC 2.8.1.2 (3-mercaptopyruvate sulphurtransferase); 0 (Thionucleosides); 2457-80-9 (5'-methylthioadenosine); 29908-03-0 (S-Adenosylmethionine); 4371-52-2 (Cysteine); 454-28-4 (Homocysteine); 58-61-7 (Adenosine); 583-92-6 (2-keto-4-methylthiobutyric acid); 7005-18-7 (Methionine); 7704-34-9 (Sulfur)

Record 19 from database: MEDLINE
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Title

Diseases of sulphur metabolism: implications for the methionine-homocysteine cycle, and vitamin responsiveness.

Author

Mudd SH

Source

Ciba Found Symp, 1979, :72, 239-58

Abstract

Sixteen inherited human diseases are now recognized, affecting most of the major steps in sulphur metabolism. Studies of patients with three types of homocystinuria have demonstrated unequivocally the major role of cystathionine formation in degradation of homocysteine, and the importance of homocysteine remethylation. Methionine balance studies of normal subjects and of a sarcosine oxidase-deficient subject have shown the predominant role of creatine synthesis in methionine utilization and permitted assessment of the rate of oxidation of the methyl group of methionine. Together, the results demonstrate that once regulatory adjustments have been made the rate of methylneogensis is nicely controlled so that labile methyl groups are made available in amounts just sufficient to meet the needs for methionine. When excess methionine is ingested the four-carbon moiety is diverted into cystathionine, the methyl group is oxidized via sarcosine and the flow of partially oxidized one-carbon units is diverted away from 5-methyltetrahydrofolate toward CO2. Studies of cystathionine synthase-deficient patients demonstrate that the capacity to respond or not to respond to pyridoxine administration is genetically controlled, probably through structural differences in mutant cystathionine synthases. However, the properties of the enzyme crucial in conferring responsiveness have not yet been identified.

Language of Publication

English

Unique Identifier

80245604

MeSH Heading (Major)

Homocysteine|*ME/PH; Metabolism, Inborn Errors|*ME; Methionine|*ME; Pyridoxine|*TU; Sulfur|*ME

MeSH Heading

Adolescence; Cystathionine beta-Synthase|ME; Homocystinuria|DT/EN/GE; Human; Methylation

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0300-5208

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 4.2.1.22 (Cystathionine beta-Synthase); 454-28-4 (Homocysteine); 65-23-6 (Pyridoxine); 7005-18-7 (Methionine); 7704-34-9 (Sulfur)

Record 20 from database: MEDLINE
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Title

Transmethylation hypothesis of schizophrenia: methionine and nicotinic acid.

Author

Nestoros JN; Ban TA; Lehmann HE

Source

Int Pharmacopsychiatry, 1977, 12:4, 215-46

Abstract

The transmethylation hypothesis of schizophrenia was reviewed with considerations that large doses of methionine when combined with a monoamine oxidase inhibitor lead to exacerbation of psychotic symptoms in a significant percentage of chronic schizophrenic patients. It was noted that nicotinic acid in the dosage of 3,000 mg/day can neither prevent nor counteract the psychopathology thus induced.

Language of Publication

English

Unique Identifier

78066284

MeSH Heading (Major)

Methionine|AD/AE/*ME; Nicotinic Acids|*AD; Schizophrenia|ET/*ME

MeSH Heading

Catechol Methyltransferase|ME; Female; Human; Male; Methylation; Methyltransferases|ME; Monoamine Oxidase Inhibitors|AD

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0020-8272

Country of Publication

SWITZERLAND

 

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Record 21 from database: MEDLINE
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Title

Effects on transmethylation by high-dose 6-mercaptopurine and methotrexate infusions during consolidation treatment of acute lymphoblastic leukemia.

Author

Keuzenkamp-Jansen CW; De Abreu RA; Blom HJ; Bökkerink JP; Trijbels JM

Address

Laboratory of Pediatrics, University Hospital St. Radboud, Nijmegen, The Netherlands.

Source

Biochem Pharmacol, 1996 May 3, 51:9, 1165-71

Abstract

6-mercaptopurine (6MP) cytotoxicity is caused by thioguanine and methylthioinosine nucleotides. Thiopurine methylation occurs to a large extent in vivo and in vitro. In this reaction, S-adenosyl-L-methionine (AdoMet), produced from

and ATP, is converted into S-adenosyl-L-homocysteine (AdoHcy) which, in turn, is hydrolyzed into homocysteine. Remethylation of homocysteine into methionine is inhibited by methotrexate (MTX). In cultured lymphoblasts, AdoMet: AdoHcy ratio and DNA methylation decrease after incubation with 6MP. The aim of the present study was to investigate the influence of high-dose 6MP on the methylation capacity in children with acute lymphoblastic leukemia. Five patients received 4 courses with high-dose intravenous MTX (5' g.m-2 in 24 hr) immediately followed by high-dose 6MP (1300 mg.m-2 in 24 hr). Five control patients received high-dose MTX and oral 6MP (25 mg.m -2 daily for 8 weeks). Leucovorin rescue was started at 36 hr in both groups. In the intravenous 6MP group, 6-methylmercaptopurine, its riboside, and 6-methylmercapto-8-hydroxypurine were detectable in plasma in concentrations of 0.3-2.6 muM (6MP steady state levels: 11.6 muM). In red blood cells, mean methylthioinosine nucleotide levels were one third of those of ATP (13.1 nmol/10(8)). AdoHcy levels (10 pmol/10(8)) remained constant in both groups and AdoMet was not detectable ( < 20 pmol/10(8)). In both groups, plasma homocysteine increased and

decreased following administration of MTX. The delay in the recovery of methionine in the intravenous 6MP group after MTX infusion is probably the result of an increased demand on methyl groups during 6MP infusion.

Language of Publication

English

Unique Identifier

96221547

MeSH Heading (Major)

Antimetabolites, Antineoplastic|AD/PK/*TU; Antineoplastic Agents, Combined|AD/*TU; Leukemia, Lymphocytic, Acute, L1|*DT

MeSH Heading

Child; Erythrocytes|ME; Homocysteine|BL; Human; Methionine|BL; Methotrexate|AD/PK; Methylation; Purine Nucleotides|BL; S-Adenosylhomocysteine|BL; S-Adenosylmethionine|BL; Support, Non-U.S. Gov't; 6-Mercaptopurine|AD/PK

Publication Type

JOURNAL ARTICLE

ISSN

0006-2952

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Antimetabolites, Antineoplastic); 0 (Antineoplastic Agents, Combined); 0 (Purine Nucleotides); 29908-03-0 (S-Adenosylmethionine); 454-28-4 (Homocysteine); 50-44-2 (6-Mercaptopurine); 59-05-2 (Methotrexate); 7005-18-7 (Methionine); 979-92-0 (S-Adenosylhomocysteine)

Record 22 from database: MEDLINE
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Title

Isolation of the murine S100 protein MRP14 (14 kDa migration-inhibitory-factor-related protein) from activated spleen cells: characterization of post-translational modifications and zinc binding.

Author

Raftery MJ; Harrison CA; Alewood P; Jones A; Geczy CL

Address

Immunology Group, Heart Research Institute, Camperdown, New South Wales, Australia.

Source

Biochem J, 1996 May 15, 316 ( Pt 1):, 285-93

Abstract

MRP14 (macrophage migration-inhibitory factor-related protein of molecular mass 14 kDa) is an S100 calcium binding protein constitutively expressed in human neutrophils which may be associated with cellular activation/inflammation. Murine MRP14 expression was up-regulated following concanavalin A activation of spleen cells, and the protein was isolated from conditioned medium in high yield (approx. 500 ng/ml). MRP14 had a mass of 12972 +/- 2 Da by electrospray ionization MS, whereas the theoretical mass derived from the cDNA sequence, after removal of the initiator Met, was 12918 Da, suggesting that the protein was post-translationally modified. We identified four post-translational modifications of MRP14: removal of the N-terminal Met, N-terminal acetylation, disulphide bond formation between Cys79 and Cys90, and 1-methylation of His106; the calculated mass was then 12971.8 Da. Methylation of His106 was further characterized after incubation of spleen cells with L-[methyl-3H]Met during concanavalin A stimulation. Sequential analysis of a peptide (obtained by digestion with Lys C) containing methylated His indicated that > 80% of the label in the cycle corresponded to His106, suggesting that the methyl residue was transferred from S-adenosyl-L-methionine. Comparison of the C18 reverse-phase HPLC retention times of phenylthiocarbamoyl derivatives of a hydrolysed digest peptide of MRP14 with those of standards confirmed methyl substitution on the 1-position of the imidazole ring. MRP14 bound more 85Zn2+ than the same amounts of the 10 kDa chemotactic protein (CP10) or S100 beta. Ca2+ decreased Zn2+ binding in S100 beta but it did not influence binding to MRP14, suggesting that the Zn2+ binding site was distinct from and independent of the two Ca2+ binding domains.

Language of Publication

English

Unique Identifier

96235204

MeSH Heading (Major)

Antigens, Differentiation|CH/*IP/*ME; Calcium-Binding Proteins|CH/*IP/*ME; Gene Expression Regulation|*DE; Lymphocytes|DE/*ME; Protein Processing, Post-Translational|*; Spleen|IM/*ME; Zinc|*ME/PD

MeSH Heading

Acetylation; Amino Acid Sequence; Animal; Cells, Cultured; Chromatography, High Pressure Liquid; Comparative Study; Concanavalin A|PD; Cysteine; Disulfides|AN; Histidine; Human; Lymphocyte Transformation; Methionine|ME; Methylation; Mice; Molecular Sequence Data; Neutrophils|ME; Peptide Fragments|CH/IP; Sequence Homology, Amino Acid; Spectrum Analysis, Mass; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0264-6021

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Antigens, Differentiation); 0 (Calcium-Binding Proteins); 0 (Disulfides); 0 (MRP-14 protein); 0 (Peptide Fragments); 11028-71-0 (Concanavalin A); 4371-52-2 (Cysteine); 7005-18-7 (Methionine); 7006-35-1 (Histidine); 7440-66-6 (Zinc)

Record 23 from database: MEDLINE
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Title

Effect of methionine loading on 5-methyltetrahydrofolate, S-adenosylmethionine and S-adenosylhomocysteine in plasma of healthy humans.

Author

Loehrer FM; Haefeli WE; Angst CP; Browne G; Frick G; Fowler B

Address

Metabolic Unit, University Children's Hospital Basel, Switzerland.

Source

Clin Sci (Colch), 1996 Jul, 91:1, 79-86

Abstract

1. Elevated plasma homocysteine concentration, either in the fasting state or after methionine loading, is an independent risk factor for vascular disease in man. Methionine loading has been used to investigate impaired methionine metabolism, especially of the trans-sulphuration pathway, but most studies have focused on changes in homocysteine. 2. We investigated the effect of methionine excess on total plasma homocysteine, 5-methyltetrahydrofolate (which is the active form of folate in the remethylation of homocysteine to methionine), S-adenosyl-methionine (the first metabolite of methionine) and S-adenosylmethionine) (the demethylated product of S-adenosylmethionine) over 24h in 12 healthy subjects. 3. As well as the expected increase in homocysteine (from 8.0 +/- 1.3 to 32.6 +/- 10.3 mumol/l, mean +/- SD, P < 0.001), S-adenosylmethionine showed a significant transient increase (from 37.9 +/- 25.0 to 240.3 +/- 109.2 nmol/l, P < 0.001), which correlated well with homocysteine (r2 = 0.92, P < 0.001). 5-Methyltetrahydrofolate values decreased significantly (from 23.2 +/- 7.2 to 13.1 +/- 2.9 nmol/l, P < 0.01), and gradually returned to baseline levels