Methylation
One-Carbon Units Metabolism

Author: Gianpiero Pescarmona
Date: 20/05/2010

Description

Methyl Group

Methylation targets are:

  • DNA
  • RNA
  • Proteins
    • Arginine
    • Lysine
  • Lipids
  • Hormones and neurotransmitters
  • Telomere

Methyl Donor

Methyl Transferases

DNA

DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular process. These include, embryonic development, transcription, chromatine structure, X chromosome inactivation, genomic imprinting and chromosome stability. (Robertson 2005 Nat. Rev.)

Methylation contributing to epigenetic inheritance can occur either through DNA methylation or protein methylation
DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. The bulk of mammalian DNA has about 40% of CpG sites methylated but there are certain areas, know as CpG islands which are GC rich (made up of about 65% CG residues) where none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. 1-2% of the human genome are CpG clusters and there is an inverse relationship between CpG methylation and transcriptional activity.

DNA methylation

Azacytidine-induced tumorigenesis of CHEF/18 cells: Correlated DNA methylation and chromosome changes, 1983

RNA

Proteins

Protein methylation is one type of post-translational modification.

Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence.

Identification, Quantification, and System Analysis of Protein N-ε Lysine Methylation in Anucleate Blood Platelets, 2019

charcot+marie+tooth+and+proteins+methylation

Protein Aminoacids Percentage (Width 700 px)

Proteins transferring CH3 to Lysine are older than those transferring to Arginine

DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular process. These include, embryonic development, transcription, chromatine structure, X chromosome inactivation, genomic imprinting and chromosome stability. (Robertson 2005 Nat. Rev.)

Methylation contributing to epigenetic inheritance can occur either through DNA methylation or protein methylation
DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. The bulk of mammalian DNA has about 40% of CpG sites methylated but there are certain areas, know as CpG islands which are GC rich (made up of about 65% CG residues) where none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. 1-2% of the human genome are CpG clusters and there is an inverse relationship between CpG methylation and transcriptional activity.

DNA methylation

Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence. Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylated arginine) or one on both nitrogens (symmetric dimethylated arginine) by peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by lysine methyltransferases. Protein methylation has been most well studied in the histones. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases. Histones which are methylated on certain residues can act epigenetically to repress or activate gene expression. Protein methylation is one type of post-translational modification.

Asimmetric dimethyl arginine

Lipids

Hormones and neurotransmitters

Comments
2024-04-16T22:31:09 - Gianpiero Pescarmona

S-adenosylmethionine: nothing goes to waste, 2004

  • S-adenosylmethionine (SAM or AdoMet) is a biological sulfonium compound known as the major biological methyl donor in reactions catalyzed by methyltransferases. SAM is also used as a source of methylene groups (in the synthesis of cyclopropyl fatty acids), amino groups (in the synthesis of 7,8-diaminoperlagonic acid, a precursor of biotin), ribosyl groups (in the synthesis of epoxyqueuosine, a modified nucleoside in tRNAs) and aminopropyl groups (in the synthesis of ethylene and polyamines). Even though the mechanism of most of these reactions has not been extensively characterized, it is likely that the chemistry at work is mainly driven by the electrophilic character of the carbon centers that are adjacent to the positively charged sulfur atom of SAM. In addition, SAM, upon one-electron reduction, is a source of 5′-deoxyadenosyl radicals, which initiate many metabolic reactions and biosynthetic pathways by hydrogen-atom abstraction. SAM presents a unique situation in which all constituent parts have a chemical use.
2023-12-16T16:37:11 - Gianpiero Pescarmona

Metabolic_Intermediates_in_Tumorigenesis_and_Progression, 2019

Traditional antitumor drugs inhibit the proliferation and metastasis of tumour cells by restraining the replication and expression of DNA. These drugs are usually highly cytotoxic. They kill tumour cells while also cause damage to normal cells at the same time, especially the hematopoietic cells that divide vigorously. Patients are exposed to other serious situations such as a severe infection caused by a decrease in the number of white blood cells. Energy metabolism is an essential process for the survival of all cells, but differs greatly between normal cells and tumour cells in metabolic pathways and metabolic intermediates. Whether this difference could be used as new therapeutic target while reducing damage to normal tissues is the topic of this paper. In this paper, we introduce five major metabolic intermediates in detail, including acetyl-CoA, SAM, FAD, NAD+ and THF. Their contents and functions in tumour cells and normal cells are significantly different. And the possible regulatory mechanisms that lead to these differences are proposed carefully. It is hoped that the key enzymes in these regulatory pathways could be used as new targets for tumour therapy.

2023-12-15T11:39:42 - Gianpiero Pescarmona

Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis, 2023

LPS induced inflammation

One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages, 2019

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