Life Glow Plus Super Life Glow Life Glow Basic Bone Dense Calcium Taheebo Life Tea Germanium Colloidal Minerals Methyl Sulfonyl Methane Transfer Factor Immune Egg	Vibrant Life Home Web All VL Products Family Of Three Chelation Formulas Oral Chelation Ingredient Comparisons The Wednesday Letter Karl Loren Viewpoints Frequently Asked Questions Testimonials Free Radicals Central Page For 18 Web Sites	Vibrant Life Home Page Shopping Cart	Separate Search Page or search below
Navigation Help	Karl Loren Background	Ingredients Technical	Write To Karl Loren	Table Of Contents

S-adenosyl methionine

[SAMe]

There are reports about S-adenosyl methionine with Abstracts, applying to humans and being "Review Articles."  There is very little information about "SAM" available, and as far as I know this substance has not been commercially available except through channels importing it from Italy at extremely high prices (well over $1,000 per pound!).

You should explore the technical qualities of Microhydrin as an alternative which will probably give comparable results at less cost and which is currently available from this web site.  Click Here to read about Microhydrin.

Top

HealthGate Documents

Record 2 from database: MEDLINE
Return  To Top

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 3 from database: MEDLINE
Return  To Top

Title

Regulation of methionine synthesis in Escherichia coli.

Author

Weissbach H; Brot N

Address

Roche Research Center, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.

Source

Mol Microbiol, 1991 Jul, 5:7, 1593-7

Abstract

The biosynthesis of methionine in Escherichia coli is under complex regulation. The repression of the biosynthetic pathway by methionine is mediated by a repressor protein (MetJ protein) and S-adenosyl-methionine which functions as a corepressor for the MetJ protein. Recently, a new regulatory locus, metR, has been identified. The MetR protein is required for both metE and metH gene expression, and functions as a transactivator of transcription of these genes. MetR is a unique prokaryotic transcription activator in that it possesses a leucine zipper motif, first described for eukaryotic DNA-binding proteins. The transcriptional activity of MetR is modulated by homocysteine, the metabolic precursor of methionine. Finally, it is known that vitamin B12 can repress expression of the metE gene. This effect is mediated by the MetH holoenzyme, which contains a cobamide prosthetic group.

Language of Publication

English

Unique Identifier

92048475

MeSH Heading (Major)

Escherichia coli|*GE; Gene Expression Regulation, Bacterial|*; Methionine|BI/*GE

MeSH Heading

Bacterial Proteins|GE; Base Sequence; Homocystine|ME; Leucine Zippers; Molecular Sequence Data; Trans-Activators|GE; Vitamin B 12|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0950-382X

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (metE gene product); 0 (metR gene product); 0 (Bacterial Proteins); 0 (Trans-Activators); 462-10-2 (Homocystine); 68-19-9 (Vitamin B 12); 7005-18-7 (Methionine)

Record 4 from database: MEDLINE
Return  To Top

Title

Genomic abnormalities in hepatocarcinogenesis. Implications for a chemopreventive strategy.

Author

Pascale RM; Simile MM; Feo F

Address

Istituto di Patologia Generale dell' Universita di Sassari, Italy.

Source

Anticancer Res, 1993 Sep-Oct, 13:5A, 1341-56

Abstract

Carcinogenesis is a complex process characterized by the cumulative activation of various oncogenes and the inactivation of suppressor genes. Epigenetic mechanisms are also involved. Mutational activation of ras family genes occurs in most spontaneous or carcinogen-induced liver tumors, in susceptible mice, and less frequently in preneoplastic lesions. This suggests a pathogenetic role of these changes in hepatic carcinogenesis, in the mouse. Overexpression of various growth-related genes occurs in preneoplastic tissue during rat liver carcinogenesis, but mutational activation of protooncogenes, notably of ras family genes, seems to be a late and rare event, while c-myc amplification is a late but frequent event in both rodent and human carcinogenesis. However, mutation of the suppressor p53 gene has been found in relatively early preneoplastic lesions in rat liver, and it may be frequently seen in human hepatocellular carcinomas. The possibility that this mutation is involved in the initiation stage of liver carcinogenesis is an attractive hypothesis which needs further evaluation. DNA hypomethylation is involved in carcinogenesis, but the mechanisms underlying this effect are still elusive. Hypomethylation of growth-related genes is associated with their overexpression and this could favor overgrowth of preneoplastic liver tissue. Decrease in S-adenosyl methionine/S-adenosylhomocysteine (SAM/SAH) ratio occurs in the liver of rats fed a methyl deficient diet, which is a carcinogenic treatment, and in preneoplastic liver tissue, developing in initiated/promoted rats fed an adequate diet. The role of low SAM/SAH ratio in carcinogenesis is substantiated by the tumor chemopreventive effect of lipotropic compounds. Treatment with exogenous SAM prevents the development of preneoplastic and neoplastic lesions in rat liver. This is associated with recovery of SAM/SAH ratio, DNA methylation and inhibition of growth-related gene expression. SAM effect on prenoplastic cell growth is abolished by 5-azacytidine, a hypomethylating agent, indicating the involvement of DNA methylation. The possibility that in SAM-treated rats, methylation and inhibition of the expression of growth-related genes is implicated in growth restraint is attractive and should be further evaluated. Modulation of rat liver carcinogenesis by influencing gene expression through DNA methylation or other epigenetic mechanisms could be a new approach to chemoprevention of these tumors.

Language of Publication

English

Unique Identifier

94058075

MeSH Heading (Major)

Adenoma|*GE/PC; Carcinoma, Hepatocellular|*GE/PC; Deoxyadenosines|*AI; DNA, Neoplasm|*ME; Genes, ras|*GE; Liver Neoplasms|*GE/PC; Point Mutation|*GE; Precancerous Conditions|*GE/PC; S-Adenosylmethionine|*PD; Thionucleosides|*AI

MeSH Heading

Animal; Gene Expression Regulation, Neoplastic|DE; Genes, myc|GE; Genes, p53|GE; Methylation; Mice; Mice, Inbred Strains; Rats; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0250-7005

Country of Publication

GREECE

CAS Registry/EC Number

0 (Deoxyadenosines); 0 (DNA, Neoplasm); 0 (Thionucleosides); 2457-80-9 (5'-methylthioadenosine); 29908-03-0 (S-Adenosylmethionine)

Record 5 from database: MEDLINE
Return  To Top

Title

Mammalian small molecule methyltransferases: their structural and functional features.

Author

Fujioka M

Address

Department of Biochemistry, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Japan.

Source

Int J Biochem, 1992 Dec, 24:12, 1917-24

Abstract

Structural and functional features of mammalian S-adenosyl-methionine-dependent small molecule methyltransferases are reviewed. The methyltransferases have similar protomer molecular weights in the range of 25,000-35,000. Two common sequence motifs are found in all enzymes of known sequence. Whereas the kinetic mechanisms may be different, the methyltransferases in the free form bind S-adenosylmethionine. Most, if not all, of mammalian small molecule methyltransferases appear to have vicinal thiols in a catalytically important area of the enzyme.

Language of Publication

English

Unique Identifier

93114475

MeSH Heading (Major)

Methyltransferases|CH/*ME

MeSH Heading

Amino Acid Sequence; Animal; Human; Molecular Sequence Data; S-Adenosylmethionine|ME; Sequence Homology, Amino Acid

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0020-711X

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 2.1.1. (Methyltransferases); 29908-03-0 (S-Adenosylmethionine)

Record 6 from database: MEDLINE
Return  To Top

Title

Chemoattractant receptors on phagocytic cells.

Author

Snyderman R; Pike MC

Source

Annu Rev Immunol, 1984, 2:, 257-81

Abstract

Chemoattractant receptors on leukocytes can trigger a number of cellular responses, including the cytoskeletal reorganization, changes in cell shape, directed motility, lysosomal enzyme secretion, and activation of the respiratory burst. The dose of chemoattractants required to induce motility-related functions is generally at least ten-fold smaller than the dose required to initiate secretory and respiratory burst activities. This finding and other pharmacological evidence clearly indicate that the two types of functions (i.e. motility and secretion) are regulated differently and can be divergently modified by drugs. The affinity of the oligopeptide chemoattractant receptor on polymorphonuclear leukocytes and macrophages is heterogeneous and dynamically regulated by guanine nucleotides and prior agonist exposure. High- and low-affinity forms of the oligopeptide receptor have been identified by direct binding studies. Our data suggest that low doses of agonists can initiate interconversion of low- and high-affinity states of that portion of chemoattractant receptors regulated by guanine nucleotides. On the other hand, high doses of agonists sufficient to induce chemotactic desensitization, lysosomal enzyme secretion, and the respiratory burst lead to the formation of a new population of high-affinity receptors. These binding sites are insensitive to the effects of guanine nucleotides and appear to be rapidly internalized. Transmethylation reactions mediated by S-adenosyl methionine are required for the activation of a phospholipase and release of arachidonate from leukocytes by chemotactic factors. We suggest that release of arachidonate from membrane phospholipid activates and translocates a cytosolic but loosely membrane-associated protein kinase C into the membrane and that this kinase participates in stimulus-response coupling of chemoattractant receptors.

Language of Publication

English

Unique Identifier

86025932

MeSH Heading (Major)

Chemotactic Factors|*PH; Chemotaxis, Leukocyte|*; Macrophages|*PH; Neutrophils|*PH; Receptors, Immunologic|*PH

MeSH Heading

Animal; Cell Movement; Complement 5|PH; Guanine Nucleotides|PH; Human; Leukotriene B4|PH; Macromolecular Systems; Membrane Lipids|PH; Methylation; Protein Binding; Protein Kinase C|PH; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0732-0582

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 2.7.1.- (Protein Kinase C); 0 (Chemotactic Factors); 0 (Complement 5); 0 (Guanine Nucleotides); 0 (Macromolecular Systems); 0 (Membrane Lipids); 0 (Receptors, Immunologic); 71160-24-2 (Leukotriene B4); 80295-54-1 (Complement 5a)

Record 7 from database: MEDLINE
Return  To Top

Title

Antidepressants. A comparative review of the clinical pharmacology and therapeutic use of the 'newer' versus the 'older' drugs.

Author

Rudorfer MV; Potter WZ

Address

Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland.

Source

Drugs, 1989 May, 37:5, 713-38

Abstract

Supplementing but not supplanting the original series of tricyclic and monoamine oxidase (MAO) inhibitor compounds, a new generation of antidepressant medications has been developed and marketed throughout the past decade. Constituting a more diverse group of drugs than the standard agents, the newer drugs in general have more selective acute biochemical actions (reuptake blockade of a single neurotransmitter, inhibition of 1 subtype of MAO), enabling more precise targeting of symptoms and avoiding common antidepressant-associated side effects, especially anticholinergic and cardiovascular effects. Moreover, a number of recent additions to this group, such as bupropion and ademetionine (S-adenosyl-methionine), incorporate novel mechanisms of action, challenging previous concepts of how antidepressants work, and offering opportunities for research into the pathophysiology of mood disorders. Caution in prescribing the newer antidepressants must be applied, however, as recent experience, e.g. with nomifensine, suggests that unforeseen toxicities may not appear until a medication has been in use for several years.

Language of Publication

English

Unique Identifier

89305272

MeSH Heading (Major)

Antidepressive Agents|CL/*PD/TU; Depressive Disorder|*DT

MeSH Heading

Animal; Comparative Study; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Antidepressive Agents)

Record 8 from database: MEDLINE
Return  To Top

Title

Neuropharmacology of S-adenosyl-L-methionine.

Author

Baldessarini RJ

Address

Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

Source

Am J Med, 1987 Nov 20, 83:5A, 95-103

Abstract

The metabolite S-adenosyl-L-methionine (SAMe), when prepared as the stable p-toluene-sulfonate complex of its sulfate salt and given parenterally in high doses, appears to have mood-elevating effects in depressed adults. The material is remarkably well tolerated when given by injection or intravenous infusion for this purpose, even in elderly or demented patients. Assuming that the toluene sulfonate component is inert, SAMe appears to have central neuropharmacologic effects after systemic injection in high doses. Nevertheless, the functional consequences of these remain unclear and, indeed, the ability of exogenous SAMe to reach the brain, and especially neuronal cytoplasm, is limited. SAMe has small effects on monoamine metabolism and, after injection, appears to have effects on the microviscosity of cell membranes that may be related to stimulation of phospholipid synthesis. The recent introduction of an orally administered form of SAMe for use in the treatment of osteoarthritis promises to stimulate further study of SAMe in disease-associated depression, major depressive disorder, and other neuropsychiatric conditions.

Language of Publication

English

Unique Identifier

88074429

MeSH Heading (Major)

Affect|*DE; S-Adenosylmethionine|*PD/PK/TU

MeSH Heading

Administration, Oral; Animal; Catecholamines|ME; Cell Membrane|ME; Depressive Disorder|DT; Human; Infusions, Intravenous; Phospholipids|ME; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0002-9343

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Catecholamines); 0 (Phospholipids); 29908-03-0 (S-Adenosylmethionine)

Record 9 from database: MEDLINE
Return  To Top

Title

Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease.

Author

Chawla RK; Bonkovsky HL; Galambos JT

Address

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Source

Drugs, 1990, 40 Suppl 3:, 98-110

Abstract

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.

Language of Publication

English

Unique Identifier

91184037

MeSH Heading (Major)

Liver Diseases|DT/*ME; S-Adenosylmethionine|*ME/PD/TU

MeSH Heading

Animal; Cell Membrane|DE/ME; Depressive Disorder|DT; Human; Methylation

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

29908-03-0 (S-Adenosylmethionine)

Record 10 from database: MEDLINE
Return  To Top

Title

S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism.

Author

Friedel HA; Goa KL; Benfield P

Address

ADIS Drug Information Services, Auckland, New Zealand.

Source

Drugs, 1989 Sep, 38:3, 389-416

Abstract

S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to virtually all body tissues and fluids. It is of fundamental importance in a number of biochemical reactions involving enzymatic transmethylation, contributing to the synthesis, activation and/or metabolism of such compounds as hormones, neurotransmitters, nucleic acids, proteins, phospholipids and certain drugs. The administration of a stable salt of SAMe, either orally or parenterally, has been shown to restore normal hepatic function in the presence of various chronic liver diseases (including alcoholic and non-alcoholic cirrhosis, oestrogen-induced and other forms of cholestasis), to prevent or reverse hepatotoxicity due to several drugs and chemicals such as alcohol, paracetamol (acetaminophen), steroids and lead, and to have antidepressant properties. In all of these studies SAMe has been very well tolerated, a finding of great potential benefit given the well-known adverse effects of tricyclic antidepressants with which it has been compared in a few trials. Thus, with its novel mechanisms of action and good tolerability, SAMe is an interesting new therapeutic agent in several diverse disease conditions, but its relative value remains to be determined in appropriate comparisons with other treatment modalities in current use.

Language of Publication

English

Unique Identifier

90032426

MeSH Heading (Major)

S-Adenosylmethionine|ME/*PD/TU

MeSH Heading

Affective Disorders|DT; Animal; Clinical Trials; Comparative Study; Double-Blind Method; Human; Liver Diseases|DT

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

29908-03-0 (S-Adenosylmethionine)

Record 11 from database: MEDLINE
Return  To Top

Title

Review article: S-adenosyl-L-methionine--a new therapeutic agent in liver disease?

Author

Osman E; Owen JS; Burroughs AK

Address

University Department of Medicine, Royal Free Hospital and School of Medicine, London, UK.

Source

Aliment Pharmacol Ther, 1993 Feb, 7:1, 21-8

Abstract

The established biochemical effects of exogenous S-Adenosyl-L-Methionine (SAMe) are diverse and are still being explored in liver disease. Putative therapeutic effects could be exerted via different mechanisms. The established deficiency of SAMe synthetase in cirrhosis could by bypassed by exogenous SAMe, leading to increased levels of sulphur-containing amino acids and glutathione which would protect against oxidant stress and drug-induced hepatotoxicity (for example, paracetamol). Furthermore SAMe could act by improving membrane fluidity, and thus potentially improve or restore the function of receptors, enzymes and transporters in the cell surface. Membrane fluidity is known to be affected by alterations in cell membrane lipid composition in chronic liver disease. Very few therapeutic agents are effective for the symptomatic or specific treatment of chronic liver disease. SAMe has established biochemical and biophysical effects which in pilot studies ameliorate symptoms and biochemical parameters of cholestasis. Moreover, abnormalities in liver function tests (including transaminase values) also improve. Before SAMe can be considered as an established therapy for patients with hepatic disease, long-term controlled clinical trials of SAMe are needed to assess the benefit for patients' symptoms, well being, histological changes and progression of liver disease.

Language of Publication

English

Unique Identifier

93176922

MeSH Heading (Major)

Liver Diseases|*DT; S-Adenosylmethionine|*TU

MeSH Heading

Animal; Female; Human; Pregnancy

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0269-2813

Country of Publication

ENGLAND

CAS Registry/EC Number

29908-03-0 (S-Adenosylmethionine)

Record 12 from database: MEDLINE
Return  To Top

Title

Metabolism of exogenous S-adenosyl-L-methionine in patients with liver disease.

Author

Kaye GL; Blake JC; Burroughs AK

Address

Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital, London, UK.

Source

Drugs, 1990, 40 Suppl 3:, 124-8

Abstract

S-Adenosyl-L-methionine (SAMe) is an important methyl group donor for many biochemical reactions. It is widespread in body tissues, including the liver, and is metabolised via 3 main metabolic pathways: transmethyltion, trans-sulphuration and amino-propylation. In chronic liver disease these pathways are impaired, the major abnormality being a reduction in SAMe-synthetase activity. Exogenous SAMe may overcome the effects of impaired SAMe-synthetase activity. Exogenous SAMe is stable in digestive juices and, although well absorbed orally, bioavailability is reduced because of a significant first pass effect in the liver. Dose-dependent peak plasma levels are achieved within 3 to 6 hours of oral administration and plasma levels approach baseline after 24 hours. Volumes of distribution are small. The metabolism of exogenous SAMe appears to follow the known pathways of endogenous SAMe metabolism and the initial data suggest that the process is largely unaffected in patients with chronic liver disease.

Language of Publication

English

Unique Identifier

91184029

MeSH Heading (Major)

Liver Diseases|*ME; S-Adenosylmethionine|*ME/PK

MeSH Heading

Animal; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

29908-03-0 (S-Adenosylmethionine)

Record 13 from database: MEDLINE
Return  To Top

Title

Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis.

Author

Almasio P; Bortolini M; Pagliaro L; Coltorti M

Address

Clinica Medica R, Università di Palermo, Italy.

Source

Drugs, 1990, 40 Suppl 3:, 111-23

Abstract

Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.

Language of Publication

English

Unique Identifier

91184028

MeSH Heading (Major)

Cholestasis, Intrahepatic|*DT/ET; S-Adenosylmethionine|PH/*TU

MeSH Heading

Animal; Bile Acids and Salts|AE/BL; Bilirubin|BL; Female; Human; Pregnancy; Pregnancy Complications|DT; 1-Naphthylisothiocyanate|TO

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Bile Acids and Salts); 29908-03-0 (S-Adenosylmethionine); 551-06-4 (1-Naphthylisothiocyanate); 635-65-4 (Bilirubin)

Record 14 from database: MEDLINE
Return  To Top

Title

Structure and function of DNA methyltransferases.

Author

Cheng X

Source

Annu Rev Biophys Biomol Struct, 1995, 24:, 293-318

Abstract

In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. In eukaryotes, DNA methylation has been implicated in the control of several cellular processes, including differentiation, gene regulation, and embryonic development. Structural work on HhaI DNA methyltransferase demonstrates that the substrate nucleotide is completely flipped out of the helix during the modification reaction and has provided much insight into the enzymatic properties of S-adenosyl-L-methionine (SAM)-dependent DNA-modifying enzymes. Structural comparison of three enzymes, HhaI C5-cytosine methyltransferase, TaqI N6-adenine methyltransferase, and catechol O-methyltransferase, reveals a striking similarity in protein folding and indicates that many SAM-dependent methyltransferases have a common catalytic-domain structure. This feature permits the prediction of tertiary structure for other DNA, RNA, protein, and small-molecule methyltransferases from their amino acid sequences, including the eukaryotic CpG methyltransferases.

Language of Publication

English

Unique Identifier

95392155

MeSH Heading (Major)

Adenine|*ME; Cytosine|*ME; DNA|*ME; Methyltransferases|*CH/*ME

MeSH Heading

Amino Acid Sequence; Binding Sites; Catechol O-Methyltransferase|CH/ME; DNA (Cytosine-5-)-Methyltransferase|CH/ME; Methylation; Molecular Sequence Data; Protein Conformation; S-Adenosylmethionine|ME; Site-Specific DNA Methyltransferase (Cytosine-Specific)|CH/ME; Site-Specific DNA-Methyltransferase (Adenine-Specific)|CH/ME; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

1056-8700

Country of Publication

UNITED STATES

Record 15 from database: MEDLINE
Return  To Top

Title

Interaction of alcohol with other drugs and nutrients. Implication for the therapy of alcoholic liver disease.

Author

Lieber CS

Address

Section of Liver Disease and Nutrition, Bronx Veterans Affairs Medical Center, New York.

Source

Drugs, 1990, 40 Suppl 3:, 23-44

Abstract

Two decades of research in ethanol metabolism have culminated in the molecular elucidation of an ethanol-inducible cytochrome P450 (P450IIE1) which is not only involved with ethanol metabolism and ethanol tolerance, but also with the activation of a number of xenobiotics. The unique ability of P450IIE1 to activate xenobiotic agents now appears to be responsible for the increased susceptibility of the heavy drinker to hepatotoxic industrial solvents, commonly used drugs, over-the-counter medications and chemical carcinogens. It also explains some of the interaction of ethanol with nutritional factors, such as hepatic vitamin A: enhanced microsomal degradation of retinoids (together with hepatic mobilisation) promotes depletion. Treatment, however, is complicated by the fact that ethanol also enhances the toxicity of excess vitamin A. All pathways of ethanol metabolism result in the production of acetaldehyde, the toxicity of which has been reviewed (Lieber 1982). New aspects discussed here include the formation of acetaldehyde-protein adducts and an associated immune response that may play a pathogenic role. Also discussed are the implications of ethanol-induced alterations in microtubules, mitochondria and plasma membranes, as they relate, in part, to accompanying acetaldehyde-induced toxicity, to the production of free radicals or to lipid peroxidation-mediated injury associated with glutathione depletion. There is also depletion of S-adenosyl-L-methionine (SAMe). Administration of synthetic SAMe results in a partial correction of the SAMe depletion and a consequent restoration of glutathione levels. Other beneficial effects of SAMe include a significant attenuation of the increase in plasma aspartate transaminase and glutamate dehydrogenase activities. Mitochondrial damage, including giant forms, documented by light and electron microscopy, is also attenuated by SAMe. Thus, the new understanding of the pathophysiology of alcohol-induced liver damage has led to more successful therapy with drugs and nutritional factors.

Language of Publication

English

Unique Identifier

91184030

MeSH Heading (Major)

Alcohol, Ethyl|*ME; Drugs|*ME; Hepatitis, Alcoholic|DT/*ME/PP; Microsomes, Liver|DE/EN/*ME

MeSH Heading

Animal; Dietary Proteins|ME; Drug Interactions; Human; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Vitamin A|ME; Vitamin E|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0012-6667

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Dietary Proteins); 0 (Drugs); 11103-57-4 (Vitamin A); 1406-18-4 (Vitamin E); 64-17-5 (Alcohol, Ethyl)

Record 16 from database: MEDLINE
Return  To Top

Title

GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect.

Author

Fernández Checa JC; Kaplowitz N; García Ruiz C; Colell A; Miranda M; Marí M; Ardite E; Morales A

Source

Am J Physiol, 1997 Jul, 273:1 Pt 1, G7-17

Abstract

Mitochondria generate reactive oxygen species (ROS) as byproducts of molecular oxygen consumption in the electron transport chain. Most cellular oxygen is consumed in the cytochrome-c oxidase complex of the respiratory chain, which does not generate reactive species. The ubiquinone pool of complex III of respiration is the major site within the respiratory chain that generates superoxide anion as a result of a single electron transfer to molecular oxygen. Superoxide anion and hydrogen peroxide, derived from the former by superoxide dismutase, are precursor of hydroxyl radical through the participation of transition metals. Glutathione (GSH) in mitochondria is the only defense available to metabolize hydrogen peroxide. A small fraction of the total cellular GSH pool is sequestered in mitochondria by the action of a carrier that transports GSH from the cytosol to the mitochondrial matrix. Mitochondria are not only one of the main cellular sources of ROS, they also are a key target of ROS. Mitochondria are subcellular targets of cytokines, especially tumor necrosis factor (TNF); depletion of GSH in this organelle renders the cell more susceptible to oxidative stress originating in mitochondria. Ceramide generated during TNF signaling leads to increased production of ROS in mitochondria. Chronic ethanol-fed hepatocytes are selectively depleted of GSH in mitochondria due to a defective operation of the carrier responsible for transport of GSH from the cytosol into the mitochondrial matrix. Under these conditions, limitation of the mitochondrial GSH pool represents a critical contributory factor that sensitizes alcoholic hepatocytes to the prooxidant effects of cytokines and prooxidants generated by oxidative metabolism of ethanol. S-adenosyl-L-methionine prevents development of the ethanol-induced defect. The mitochondrial GSH carrier has been functionally expressed in Xenopus laevis oocytes microinjected with mRNA from rat liver. This critical carrier displays functional characteristics distinct from other plasma membrane GSH carriers, such as its ATP dependency, inhibitor specificity, and the size class of mRNA that encode the corresponding carrier, suggesting that the mitochondrial carrier of GSH is a gene product distinct from the plasma membrane transporters.

Language of Publication

English

Unique Identifier

97396313

MeSH Heading (Major)

Ethanol|*PD; Glutathione|*ME; Mitochondria|DE/*ME; Oxidative Stress|*PH; Tumor Necrosis Factor|PD/*PH

MeSH Heading

Animal; Biological Transport; Cytosol|ME; Human; Liver|DE/ME; Mitochondria, Liver|DE/ME; Models, Biological; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Ubiquinol-Cytochrome-c Reductase|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0002-9513

Country of Publication

UNITED STATES

Record 17 from database: MEDLINE
Return  To Top

Title

Rules of molecular geometry for predicting carcinogenic activity of unsubstituted polynuclear aromatic hydrocarbons.

Author

Flesher JW; Myers SR

Address

Department of Pharmacology, Albert B. Chandler Medical Center, University of Kentucky, Lexington 40536.

Source

Teratog Carcinog Mutagen, 1991, 11:1, 41-54

Abstract

The rules of molecular geometry for predicting carcinogenic activity of polynuclear aromatic hydrocarbons (PAH) have been applied to a series of 50 unsubstituted PAH, and predicted carcinogenic activity is in good agreement with the results of testing for complete carcinogenic activity in mice and/or rats. The rules were developed from a knowledge of the center or centers of highest chemical or biochemical reactivity and are consistent with a unified hypothesis which states that the first step in the metabolic activation of unsubstituted PAH is the biochemical introduction of a methyl group. This bioalkylation reaction 1) takes place between certain PAH and S-adenosyl-L-methionine and is catalyzed by cytosolic methyltransferase, 2) offers a means of probing for centers of reactivity in PAH, 3) provides a biochemical link between unsubstituted preprocarcinogens of aromatic type ArX and alkyl-substituted procarcinogens of aromatic type ArCH2X (where X = H), and 4) makes it possible to include compounds of both aromatic types, in a consistent theory of aromatic hydrocarbon activation which incorporates alkyl substitution. The present study reveals that there are structural determinants of carcinogenicity.

Language of Publication

English

Unique Identifier

91313543

MeSH Heading (Major)

Carcinogens|*; Polycyclic Hydrocarbons|CH/*TO

MeSH Heading

Animal; Models, Molecular; Molecular Structure; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0270-3211

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Carcinogens); 0 (Polycyclic Hydrocarbons)

Record 18 from database: MEDLINE
Return  To Top

Title

DNA modification by methyltransferases.

Author

Cheng X

Source

Curr Opin Struct Biol, 1995 Feb, 5:1, 4-10

Abstract

Enzymatic methylation of DNA plays important roles in both prokaryotes and eukaryotes. Structural study of the HhaI DNA methyltransferase has provided considerable insight into the chemistry of C5-cytosine methylation. The DNA-protein complex reveals a substrate cytosine flipped out of the double helix during the reaction, and a novel two-loop DNA-binding motif used for both sequence recognition and flipping the base. Structural comparison of HhaI C5-cytosine methyltransferase, TaqI N6-adenine methyltransferase, and catechol O-methyltransferase reveals a common catalytic domain structure, which might be universal among S-adenosyl-L-methionine (SAM)-dependent methyltransferases.

Language of Publication

English

Unique Identifier

95292061

MeSH Heading (Major)

DNA|*CH/*ME; Methyltransferases|CH/*PD; Nucleic Acid Conformation|*DE

MeSH Heading

Amino Acid Sequence; Animal; 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

0959-440X

Country of Publication

ENGLAND

Record 19 from database: MEDLINE
Return  To Top

Title

Polyamines in mammalian ageing: an oncological problem, too? A review.

Author

Scalabrino G; Ferioli ME

Source

Mech Ageing Dev, 1984 Aug, 26:2-3, 149-64

Abstract

This review surveys the literature about changes in polyamine contents and levels of activity of the enzymes involved in the polyamine biosynthetic pathway in organs of ageing mammals. The literature about changes in the polyamine levels in physiological fluids in healthy ageing humans is also reviewed. Generally speaking, decreases in the levels of the main polyamines (noticeably putrescine and spermidine) are observed in different mammalian organs with ageing. The polyamine levels in serum and in urine of healthy human beings are also age-related, declining progressively with increasing age. Some major enzymes (i.e., ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) involved in the polyamine biosynthetic pathway show similar trends. Hormonal induction of ornithine decarboxylase activity is strongly reduced in organs of aged animals, as it is in neoplastic organs. There is also some evidence for an age-related decrease in the level of ornithine decarboxylase and its inducibility in mammalian cells cultured in vitro. Some in vitro effects of spermidine and spermine on aged structures or systems are briefly summarized. There is no evidence yet that this generally reduced capacity of mammalian aged organs for polyamine biosynthesis is one of the factors responsible for the well known high incidence of some neoplasias in elderly humans. In view of the typical stimulatory effects of the tumour promoters on polyamine biosynthesis in target tissues and the effects of senescence on the same metabolic pathway, it can be excluded that the ageing process has a tumour promoting effect by itself. However, although the exact mechanism responsible for the increased occurrence of some tumors during mammalian senescence is still obscure, there are enough experimental data (both in humans and in animals) to indicate that the reduced polyamine biosynthetic capacity of aged mammals can account for the slower course of some tumors in elderly patients.

Language of Publication

English

Unique Identifier

85011406

MeSH Heading (Major)

Aging|*; Neoplasms|*ET/ME; Polyamines|*ME

MeSH Heading

Animal; Comparative Study; Human; Male; Ornithine Decarboxylase|ME; Putrescine|ME; Rats; S-Adenosylmethionine Decarboxylase|ME; Spermidine|ME; Spermine|ME; Tissue Distribution

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0047-6374

Country of Publication

SWITZERLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); EC 4.1.1.50 (S-Adenosylmethionine Decarboxylase); 0 (Polyamines); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 71-44-3 (Spermine)

Record 20 from database: MEDLINE
Return  To Top

Title

The formation of internal 6-methyladenine residues in eucaryotic messenger RNA.

Author

Tuck MT

Address

Department of Chemistry, Ohio University, Athens 45701.

Source

Int J Biochem, 1992 Mar, 24:3, 379-86

Abstract

1. The formation of internal 6-methyladenine (m6A) residues in eucaryotic messenger RNA (mRNA) is a postsynthetic modification in which S-adenosyl-L-methionine (SAM) serves as the methyl donor. 2. Of the methyl groups incorporated into mature mRNA 30-50% occur in m6A residues. 3. Although most cellular and certain viral mRNAs contain at least one m6A residue, some transcripts such as those coding for histone and globin are completely lacking in this modification. 4. 6-Methyladenine residues have also been localized to heterogeneous nuclear RNA (HnRNA), and for the most part these residues are conserved during mRNA processing. 5. In all known cases, the m6A residues are also found in a strict consensus sequence, Gm6AC or Am6AC, within the transcript. 6. Although the biological significance of internal adenine methylation in eucaryotic mRNA remains unclear, a great deal of research has indicated that this modification may be required for mRNA transport to the cytoplasm, the selection of splice sites or other RNA processing reactions.

Language of Publication

English

Unique Identifier

92201447

MeSH Heading (Major)

Adenine|*AA/CH/ME; Eukaryotic Cells|*ME; RNA, Messenger|CH/*ME

MeSH Heading

Animal; Human; Methylation; S-Adenosylmethionine|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0020-711X

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (RNA, Messenger); 29908-03-0 (S-Adenosylmethionine); 443-72-1 (6-methyladenine); 73-24-5 (Adenine)

 

---

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)

[ Home ] [ Up ] [ Dr. Scott M. Grundy ] [ Methionine ] [ Summary And Link Page for data about The Amino Acid Ornithine ] [ SAM --S-adenosyl methionine Research Reports ] [ Phenylalanine ] [ Summary And Link Page for data about The Amino Acid Arginine ]

SUBSCRIBE:  The Wednesday Letter is a free electronic monthly newsletter written and published by Karl Loren.  You can view more than 50 back issues of this publication by clicking here.  The Wednesday Letter subscription list is maintained on a secure server, no name is ever given or sold to anyone, and it is never used except for this Newsletter.  It is automatically published on the Tuesday night just before the first Wednesday of every month.  You can subscribe to this free monthly electronic letter by entering your eMail address and name below.  You will then automatically receive a request for confirmation, sent to whatever address you have entered.  If you do NOT receive this confirmation request, then you will not be subscribed.  There may have been an error with your address and you should resubmit.  The letter is never sent twice to the same address -- so you do not have to worry about a duplicate subscription.  When you receive this confirmation request you must reply to it, or your subscription will not become active.  No one can subscribe your name, and address, without you being notified, and if you get an unwanted notice of subscription you only need to DO NOTHING and the subscription will NOT be active.

REMOVAL:  You can remove yourself from the subscription list in several different ways.  Click here to read about this entire newsletter system.  Every edition of The Wednesday Letter is delivered to your address with YOUR name and address in view on the letter, with a link that allows you to remove THAT name from the subscription list.  If you try to send this removal message from an address different from the one you used to send in your original confirmation, then you will get a warning notice first, sent to the subscription address, asking you to confirm that you want to be removed from the list -- by replying to THAT request for confirmation, you will then be automatically removed.  Thus, no one else can unsubscribe you, from some other computer, without your knowledge.  But, if you send in the unsubscribe notice from the same machine used to receive the Letter, then the removal from the subscription list is automatic.

Personal Message:  When you send a personal message to Karl Loren, you will receive a personal reply as per his instructions.  Karl pledges that every personal message will get a personal answer. When you provide your mail address, we will send you free information including our free catalog and a cassette tape lecture by Karl Loren about heart disease, no charge, by mail, even if outside the US.  You can select particular information you would like to receive, along with the free cassette tape and catalog.

You can reach Vibrant Life in many ways, including by mail to Vibrant Life, 2808 N. Naomi St., Burbank, CA 91504.  Within the US and Canada, use the toll free number:  (800) 523-4521, the local number:  (818) 558-1799, the FAX:  (818) 558-7299, eMail to kimberly@oralchelation.com or any one of the hundreds of message forms throughout the 50 web sites.  Vibrant Life normally ships the same day we get an order.  There are message forms on each of the 100,000+ pages on this and other sites where you can communicate with Vibrant Life.  Check out our companion site, at:  http://www.oralchelation.net where Karl's 2000 page book is published.  Karl Loren is the author and webmaster for this BOOK, as well as for another web site about ORAL CHELATION.  His personal philosophical articles are at PHILOSOPHY. 

Copyright © May 20, 2008 6:24 AM by Karl Loren on behalf of Vibrant Life, ALL RIGHTS RESERVED.  Permission is granted for non-commercial downloading, copying, distribution or redistribution on two conditions:  One, that some form of copyright notice is included in every copy distributed or copied, showing the copyright belonging to Vibrant Life, Burbank, CA, at www.oralchelation.com . The second condition is that the material is not to be used for any purpose contrary to the purposes and objectives of this site.  This permission does not extend to materials on this site which are copyrighted by others.