Abstract
S-adenosyl-L-methionine (SAM) is the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. SAM level in the organism decreases with aging and restoring the original levels through exogenous supplementation is an important tool for the improvement of many vital functions. Indeed, SAM deficiency may contribute to the onset of several diseases, i.e. depression, liver diseases, osteoarthritis and senile neurological disorders such as Alzheimer’s and Parkinson’s diseases. Recent evidences indicate that SAM may have an involvement in oxidative stress, a process which typically involves an alteration of cellular sulfur amino acids homeostasis. SAM is not only the principal methyl donor, but also a precursor of glutathione, the major endogenous antioxidant, whose role in counteracting oxidative stress is well known. In this review we will highlight the role of SAM not just as a methyl-donor but also as a regulator of different metabolic pathways involved in the antioxidant response in brain related disorders.
Highlights
The interaction between environmental and genetic factors plays a fundamental role in inducing and modulating the aging processes towards brain disorders
Specific nutritional factors have particular impact on one-carbon metabolism, which is a complex biochemical pathway regulated by the presence of folate, vitamin B12 and B6 and leading to the production of S-adenosyl-L-methionine (SAM), the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA
This metabolism involves three interrelated biochemical pathways: folate cycle, transsulfuration pathway and methionine cycle. These three metabolic sequences were first combined and correlated in 1964 by Laster’s group [1,2,3] giving the integrated point of view of transmethylation and transsulfuration pathways, linking sulfur amino acid metabolism to the provision of methyl groups for many biochemical processes. Normal functioning of this metabolic cycle is essential for growth and development and impairment of this metabolism; transmethylation efficiency is associated with many diseases like cardiovascular diseases [4,5], liver diseases [6,7,8,9], neural tube defects [10] and brain diseases [11,12,13,14,15,16]
Summary
Andrea Fuso, Maria d’Erme, Niccolò Miraglia, Sara Martire, Sigfrido Scarpa, Luciana Mosca3* 1Department of Surgery “P. Valdoni”, Sapienza University, Roma, Italy 2CERC/S: Lucia Foundation, Roma, Itay 3Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University, Roma, Italy; 4Gnosis S.p.A, Desio, MB, Italy Andrea Fuso, Maria d’Erme, Niccolò Miraglia, Sara Martire, Sigfrido Scarpa, Luciana Mosca3* 1Department of Surgery “P. Valdoni”, Sapienza University, Roma, Italy 2CERC/S: Lucia Foundation, Roma, Itay 3Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University, Roma, Italy; 4Gnosis S.p.A, Desio, MB, Italy
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