RGD Reference Report - Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid. - Rat Genome Database

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Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid.

Authors: Nieman, KM  Rowling, MJ  Garrow, TA  Schalinske, KL 
Citation: Nieman KM, etal., J Biol Chem 2004 Oct 29;279(44):45708-12. Epub 2004 Aug 30.
RGD ID: 1359070
Pubmed: PMID:15347642   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M408664200   (Journal Full-text)

The hepatic enzyme glycine N-methyltransferase (GNMT) plays a major role in the control of methyl group and homocysteine metabolism. Because disruption of these vital pathways is associated with numerous pathologies, understanding GNMT control is important for evaluating methyl group regulation. Recently, gluconeogenic conditions have been shown to modulate homocysteine metabolism and treatment with glucocorticoids and/or all-trans-retinoic acid (RA)-induced active GNMT protein, thereby leading to methyl group loss. This study was conducted to determine the effect of diabetes, alone and in combination with RA, on GNMT regulation. Diabetes and RA increased GNMT activity 87 and 148%, respectively. Moreover, the induction of GNMT activity by diabetes and RA was reflected in its abundance. Cell culture studies demonstrated that pretreatment with insulin prevented GNMT induction by both RA and dexamethasone. There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine beta-synthase; treatment of diabetic rats with RA prevented cystathionine beta-synthase induction. A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteine S-methyltransferase, whereas the activity of the folate-dependent enzyme methionine synthase was diminished 52%. In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteine S-methyltransferase, whereas methionine synthase activity remained diminished. These results indicate that both a diabetic condition and RA treatment have marked effects on the metabolism of methyl groups and homocysteine, a finding that may have significant implications for diabetics and their potential sensitivity to retinoids.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GnmtRatS-adenosylhomocysteine metabolic process  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GnmtRatglycine binding  TAS  RGD 
GnmtRatS-adenosylmethionine-dependent methyltransferase activity  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GnmtRatfolate metabolic pathway  TAS  RGD 
GnmtRathomocysteine metabolic pathway   IDA  RGD 
GnmtRatmethionine cycle/metabolic pathway   IDA  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Gnmt  (glycine N-methyltransferase)


Additional Information