RGD Reference Report - S-adenosylmethionine in liver health, injury, and cancer. - Rat Genome Database

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S-adenosylmethionine in liver health, injury, and cancer.

Authors: Lu, SC  Mato, JM 
Citation: Lu SC and Mato JM, Physiol Rev. 2012 Oct;92(4):1515-42. doi: 10.1152/physrev.00047.2011.
RGD ID: 7242425
Pubmed: PMID:23073625   (View Abstract at PubMed)
PMCID: PMC3698976   (View Article at PubMed Central)
DOI: DOI:10.1152/physrev.00047.2011   (Journal Full-text)

S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AHCYHumanmethionine cycle/metabolic pathway   TAS  RGD 
AMD1Humanmethionine cycle/metabolic pathway   TAS  RGD 
AhcyRatmethionine cycle/metabolic pathway   ISOAHCY (Homo sapiens) RGD 
AhcyMousemethionine cycle/metabolic pathway   ISOAHCY (Homo sapiens) RGD 
Amd1Ratmethionine cycle/metabolic pathway   ISOAMD1 (Homo sapiens) RGD 
Amd1Mousemethionine cycle/metabolic pathway   ISOAMD1 (Homo sapiens) RGD 
BHMTHumanmethionine cycle/metabolic pathway   TAS  RGD 
BhmtRatmethionine cycle/metabolic pathway   ISOBHMT (Homo sapiens) RGD 
BhmtMousemethionine cycle/metabolic pathway   ISOBHMT (Homo sapiens) RGD 
GNMTHumanmethionine cycle/metabolic pathway   TAS  RGD 
GnmtRatmethionine cycle/metabolic pathway   ISOGNMT (Homo sapiens) RGD 
GnmtMousemethionine cycle/metabolic pathway   ISOGNMT (Homo sapiens) RGD 
MAT1AHumanmethionine cycle/metabolic pathway   TAS  RGD 
MAT2AHumanmethionine cycle/metabolic pathway   TAS  RGD 
MAT2BHumanmethionine cycle/metabolic pathway   TAS  RGD 
MTRHumanmethionine cycle/metabolic pathway   TAS  RGD 
Mat1aRatmethionine cycle/metabolic pathway   ISOMAT1A (Homo sapiens) RGD 
Mat1aMousemethionine cycle/metabolic pathway   ISOMAT1A (Homo sapiens) RGD 
Mat2aRatmethionine cycle/metabolic pathway   ISOMAT2A (Homo sapiens) RGD 
Mat2aMousemethionine cycle/metabolic pathway   ISOMAT2A (Homo sapiens) RGD 
Mat2bRatmethionine cycle/metabolic pathway   ISOMAT2B (Homo sapiens) RGD 
Mat2bMousemethionine cycle/metabolic pathway   ISOMAT2B (Homo sapiens) RGD 
MtapRatmethionine cycle/metabolic pathway   ISOMTAP (Homo sapiens) RGD 
MtapMousemethionine cycle/metabolic pathway   ISOMTAP (Homo sapiens) RGD 
MtrRatmethionine cycle/metabolic pathway   ISOMTR (Homo sapiens) RGD 
MtrMousemethionine cycle/metabolic pathway   ISOMTR (Homo sapiens) RGD 
SMSHumanmethionine cycle/metabolic pathway   TAS  RGD 
SRMHumanmethionine cycle/metabolic pathway   TAS  RGD 
SmsMousemethionine cycle/metabolic pathway   ISOSMS (Homo sapiens) RGD 
SmsRatmethionine cycle/metabolic pathway   ISOSMS (Homo sapiens) RGD 
SrmRatmethionine cycle/metabolic pathway   ISOSRM (Homo sapiens) RGD 
SrmMousemethionine cycle/metabolic pathway   ISOSRM (Homo sapiens) RGD 
SRMHumanspermidine metabolic pathway  TAS  RGD 
SrmRatspermidine metabolic pathway  ISOSRM (Homo sapiens) RGD 
SrmMousespermidine metabolic pathway  ISOSRM (Homo sapiens) RGD 
SMSHumanspermine metabolic pathway  TAS  RGD 
SmsRatspermine metabolic pathway  ISOSMS (Homo sapiens) RGD 
SmsMousespermine metabolic pathway  ISOSMS (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ahcy  (adenosylhomocysteinase)
Amd1  (adenosylmethionine decarboxylase 1)
Bhmt  (betaine-homocysteine S-methyltransferase)
Gnmt  (glycine N-methyltransferase)
Mat1a  (methionine adenosyltransferase 1A)
Mat2a  (methionine adenosyltransferase 2A)
Mat2b  (methionine adenosyltransferase 2 non-catalytic beta subunit)
Mtap  (methylthioadenosine phosphorylase)
Mtr  (5-methyltetrahydrofolate-homocysteine methyltransferase)
Sms  (spermine synthase)
Srm  (spermidine synthase)

Genes (Mus musculus)
Ahcy  (S-adenosylhomocysteine hydrolase)
Amd1  (S-adenosylmethionine decarboxylase 1)
Bhmt  (betaine-homocysteine methyltransferase)
Gnmt  (glycine N-methyltransferase)
Mat1a  (methionine adenosyltransferase 1A)
Mat2a  (methionine adenosyltransferase 2A)
Mat2b  (methionine adenosyltransferase 2 non-catalytic beta subunit methionine)
Mtap  (methylthioadenosine phosphorylase)
Mtr  (5-methyltetrahydrofolate-homocysteine methyltransferase)
Sms  (spermine synthase)
Srm  (spermidine synthase)

Genes (Homo sapiens)
AHCY  (adenosylhomocysteinase)
AMD1  (adenosylmethionine decarboxylase 1)
BHMT  (betaine--homocysteine S-methyltransferase)
GNMT  (glycine N-methyltransferase)
MAT1A  (methionine adenosyltransferase 1A)
MAT2A  (methionine adenosyltransferase 2A)
MAT2B  (methionine adenosyltransferase 2 non-catalytic beta subunit)
MTR  (5-methyltetrahydrofolate-homocysteine methyltransferase)
SMS  (spermine synthase)
SRM  (spermidine synthase)


Additional Information