S-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver. More than 40 methyl transfers from SAM are known, to various substrates such as nucleic acids, proteins, lipids and secondary metabolites. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase. SAM was first discovered by Giulio Cantoni in 1952.
Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a polycation at physiological pH. Spermine is associated with nucleic acids and is thought to stabilize helical structure, particularly in viruses. It functions as an intracellular free radical scavenger to protect DNA from free radical attack. Spermine is the chemical primarily responsible for the characteristic odor of semen.
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). Class II methyltransferases contain a SET domain, which are exemplified by SET domain histone methyltransferases, and class III methyltransferases, which are membrane associated. Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. SAM is the classical methyl donor for methyltransferases, however, examples of other methyl donors are seen in nature. The general mechanism for methyl transfer is a SN2-like nucleophilic attack where the methionine sulfur serves as the leaving group and the methyl group attached to it acts as the electrophile that transfers the methyl group to the enzyme substrate. SAM is converted to S-Adenosyl homocysteine (SAH) during this process. The breaking of the SAM-methyl bond and the formation of the substrate-methyl bond happen nearly simultaneously. These enzymatic reactions are found in many pathways and are implicated in genetic diseases, cancer, and metabolic diseases. Another type of methyl transfer is the radical S-Adenosyl methionine (SAM) which is the methylation of unactivated carbon atoms in primary metabolites, proteins, lipids, and RNA.
The enzyme adenosylmethionine decarboxylase catalyzes the conversion of S-adenosyl methionine to S-adenosylmethioninamine. Polyamines such as spermidine and spermine are essential for cellular growth under most conditions, being implicated in many cellular processes including DNA, RNA and protein synthesis. S-adenosylmethionine decarboxylase (AdoMetDC) plays an essential regulatory role in the polyamine biosynthetic pathway by generating the n-propylamine residue required for the synthesis of spermidine and spermine from putrescein. Unlike many amino acid decarboxylases AdoMetDC uses a covalently bound pyruvate residue as a cofactor rather than the more common pyridoxal 5'-phosphate. These proteins can be divided into two main groups which show little sequence similarity either to each other, or to other pyruvoyl-dependent amino acid decarboxylases: class I enzymes found in bacteria and archaea, and class II enzymes found in eukaryotes. In both groups the active enzyme is generated by the post-translational autocatalytic cleavage of a precursor protein. This cleavage generates the pyruvate precursor from an internal serine residue and results in the formation of two non-identical subunits termed alpha and beta which form the active enzyme.
Spermine synthase is an enzyme that converts spermidine into spermine. This enzyme catalyses the following chemical reaction
In enzymology, a 3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a 6-O-methylnorlaudanosoline 5'-O-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a 7-methylxanthosine synthase is an enzyme that catalyzes the chemical reaction
In enzymology, an anthranilate N-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a cyclopropane-fatty-acyl-phospholipid synthase is an enzyme that catalyzes the chemical reaction
In enzymology, a putrescine N-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a (RS)-norcoclaurine 6-O-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a (S)-scoulerine 9-O-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a theobromine synthase is an enzyme that catalyzes the chemical reaction
In enzymology, a tRNA (uracil-5-)-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a sym-norspermidine synthase is an enzyme that catalyzes the chemical reaction
Caffeine synthase is a methyltransferase enzyme involved in the caffeine biosynthesis pathway. It is expressed in tea species, coffee species, and cocoa species. The enzyme catalyses the following reactions:
A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most aromatic polyamines are crystalline solids at room temperature.
Homospermidine synthase (EC 2.5.1.44) is an enzyme with systematic name putrescine:putrescine 4-aminobutyltransferase (ammonia-forming). This enzyme catalyses the following chemical reaction
BpsA is a single-module non-ribosomal peptide synthase (NRPS) located in the cytoplasm responsible for the process of creating branched-chain polyamines, and producing spermidine and spermine. It has a singular ligand in its structure involved with Fe3+ and PLIP interactions. As seen by its EC number, it is a transferase (2) that transfers an alkyl or aryl group other than methyl groups (5) (2.5.1). BpsA was first discovered in the archaea Methanococcus jannaschii and thermophile Thermococcus kodakarensis and since then has been used in a variety of applications such as being used as a reporter, researching phosphopantetheinyl transferase (PPTase), and for NRPS domain recombination experiments it can be used as a model. Both (hyper)thermophilic bacteria and euryarchaeotal archaea seem to conserve BpsA and orthologs as branches chains polyamines are crucial for survival. There is also a second type of BpsA also known as Blue-pigment indigoidine synthetase that produces the pigment indigoidine and is found in organisms like Erwinia chrysanthemi. However, not much seems to be known about this variant except that it is a synthase, and it does not yet appear to be classified under an EC number.
