Role of sulfur chirality in the chemical processes of biology

Bentley, Ronald

doi:10.1039/b418284g

Cited by 469 publications

(252 citation statements)

References 97 publications

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“…Referring to the stereochemical configurations of the sulfur and the alfa-carbon, respectively, SAM exists in two diastereoisomeric forms respect to its sulfonium ion, the S, S-and the R, S-SAM. Only the S, S-form is the biologically active, whereas in mammals there is a minor content of the R, S-SAM [31][32] from low to undetectable levels in many tissues, ranging from 1.5 and 3% of total SAM in mouse liver and rat brain, respectively [33][34]. This contrasts with the spontaneous S, S-SAM racemization to R,S-form occurring under physiological conditions.…”

Section: Sam Structure and Stabilitycontrasting

confidence: 43%

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Cavallaro¹,

Fuso²,

D’Erme³

et al. 2016

Int J Clin Nutr Diet

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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. Role of S-adenosylmethionine in the Modulation of Oxidative StressRelated Neurodegeneration Review ArticleOpen Access IntroductionThe interaction between environmental and genetic factors plays a fundamental role in inducing and modulating the aging processes towards brain disorders. Among environmental factors, diet and nutritional lifestyle have a key role in brain health through the alteration of the intake or the bioavailability of metabolites and cofactors. 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 (among other metabolites) 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 [6-9], neural tube defects [10] and brain diseases [11][12][13][14][15][16]. One-carbon metabolism alterations, low methylation and oxidative stress are all linked to Late Onset Alzheimer's Disease (LOAD) [17][18][19][20][21][22][23][24] Moreover, wide confirmed reports underline the role of SAM dependent reactions in age related neurodegeneration also showi...

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Section: Sam Structure and Stabilitycontrasting

confidence: 43%

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Cavallaro¹,

Fuso²,

D’Erme³

et al. 2016

Int J Clin Nutr Diet

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“…Additionally, besides sulforaphane, there are a number of pharmacologically relevant drugs [42], which have in their structure a sulfinyl group including the proton pump inhibitor esomeprazole [43], the vigilance promoting armodafinyl [44] , 37 and the anti-inflammatory sulindac [45].…”

Section: Chemical Synthesismentioning

confidence: 99%

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity

Elhalem

Recio

Werner

et al. 2014

European Journal of Medicinal Chemistry

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“…Chiral sulfoxides play a significant role in pharmaceuticals and in organic synthesis, as functionalized substances and as important chiral auxiliaries (3,11,15). In addition, there is a growing demand for green catalytic processes (19,27), and therefore there is a continuous search for novel and betterperforming biocatalysts.…”

Section: Discussionmentioning

confidence: 99%

“…As natural products, chiral sulfoxides possess a wide range of biological activities, from flavor and aroma precursor activities to antimicrobial properties. In addition, they are efficient auxiliaries that lead to essential asymmetric transformations (3,11). Furthermore, one of the most significant applications of chiral sulfoxides is in the pharmaceutical industry (3).…”

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confidence: 99%

Rapid Methods for High-Throughput Detection of Sulfoxides

Shainsky

Derry

Leichtmann‐Bardoogo

et al. 2009

Appl Environ Microbiol

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Enantiopure sulfoxides are prevalent in drugs and are useful chiral auxiliaries in organic synthesis. The biocatalytic enantioselective oxidation of prochiral sulfides is a direct and economical approach for the synthesis of optically pure sulfoxides. The selection of suitable biocatalysts requires rapid and reliable high-throughput screening methods. Here we present four different methods for detecting sulfoxides produced via whole-cell biocatalysis, three of which were exploited for high-throughput screening. Fluorescence detection based on the acid activation of omeprazole was utilized for high-throughput screening of mutant libraries of toluene monooxygenases, but no active variants have been discovered yet. The second method is based on the reduction of sulfoxides to sulfides, with the coupled release and measurement of iodine. The availability of solvent-resistant microtiter plates enabled us to modify the method to a high-throughput format. The third method, selective inhibition of horse liver alcohol dehydrogenase, was used to rapidly screen highly active and/or enantioselective variants at position V106 of toluene ortho-monooxygenase in a saturation mutagenesis library, using methyl-p-tolyl sulfide as the substrate. A success rate of 89% (i.e., 11% false positives) was obtained, and two new mutants were selected. The fourth method is based on the colorimetric detection of adrenochrome, a back-titration procedure which measures the concentration of the periodate-sensitive sulfide. Due to low sensitivity during whole-cell screening, this method was found to be useful only for determining the presence or absence of sulfoxide in the reaction. The methods described in the present work are simple and inexpensive and do not require special equipment.The growing demand for green catalytic processes has increased the utilization of enzymes as industrial biocatalysts for the synthesis of fine chemicals (6,19,20). As a consequence, there is a continuous search for novel or improved biocatalysts. In order to find an appropriate candidate for a process, various sources of enzymes must be screened for activity (23). Therefore, a sensitive, reproducible, accurate, and simple highthroughput screening method is a key prerequisite for the development of biocatalytic processes on an industrial scale (32, 39).Screening systems are divided into three different classes. The first class contains assays applicable to testing growing or resting microbial colonies for enzymatic activity directly on agar plates (23), for example, detection of epoxide hydrolase activity on butane oxide by use of safranin O. Oxidation of the 1,2-diol product by Escherichia coli modified the membrane potential and led to accumulation of the red dye in the colonies producing active enzyme (34). In another study, the spontaneous oxidation of substituted catechols to brown-red quinones was used to screen random libraries of whole cells expressing toluene monooxygenases (TMOs) for regioselective oxidation of substituted phenols (12, 30). The positive cl...

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Role of sulfur chirality in the chemical processes of biology

Cited by 469 publications

References 97 publications

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity

Rapid Methods for High-Throughput Detection of Sulfoxides

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