Excess S-adenosylmethionine inhibits methylation via catabolism to adenine

Fukumoto, Kazuhiro; Ito, Kakeru; Saer, Benjamin; Taylor, G.N.; Ye, Shiqi; Yamano, Mayu; Toriba, Yuki; Hayes, Andrew; Okamura, Hitoshi; Fustin, Jean‐Michel

doi:10.1038/s42003-022-03280-5

Cited by 22 publications

(17 citation statements)

References 83 publications

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“…Metabolite quantification by LC-MS/MS was performed by our BioMS technology platform as previously described 13 .…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that circadian rhythms that rely on transcription-translation feedback loops are particularly sensitive to pharmacological or dietary interventions targeting the methyl cycle, and that many mRNAs coding for enzymes involved in 1-carbon metabolism have circadian rhythms 13,[17][18][19] . Together with the fact that NASH and liver fibrosis, both conditions driven by the MCD diet, are exacerbated by circadian misalignments 20 , this intimate link between methyl metabolism and circadian rhythms indicate that the MCD diet may also affect the circadian rhythms of the animal, which perhaps contribute to the pathologies observed in this model.…”

Section: Introductionmentioning

confidence: 99%

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Dietary methionine/choline deficiency affects behavioural and molecular circadian rhythms

Saer,

Taylor,

Hayes

et al. 2024

Preprint

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The feeding/fasting cycles controlled by our circadian clock impose great daily metabolic and physiological changes, and yet investigations into the consequences of metabolic deficiencies, either dietary or genetic, have often ignored the time of day or the circadian time of the animals or subjects. In addition, these deficiencies may themselves disrupt our circadian clock, causing secondary metabolic, physiological and behavioural disorders. Dietary methionine/choline deficiency in rodents is a common model for human non-alcoholic steatohepatitis, but methionine and choline are nutrients essential for many other processes beyond fatty acid synthesis in the liver, including biological methylations and 1-carbon metabolism, regulation of translation notably via the mTOR pathway, phospholipid synthesis, polyamine pathway and glutathione synthesis. We have previously shown that circadian rhythms in many organisms are highly sensitive to deficiency or excesses of 1-carbon metabolites. Using a methionine/choline deficient diet in mice, we illustrate the nutrigenomic crosstalk between circadian rhythms and 1-carbon metabolism. We show not only that circadian locomotor activity behaviour is profoundly, rapidly and reversibly affected by methionine/choline deficiency, but also that the effects of methionine/choline deficiency on gene expression and 1-carbon metabolites are dependent on circadian time, illustrating the importance of considering circadian rhythms in metabolic studies. This study also highlights the impact of what we eat, or don't, on our behaviour and biological rhythms.

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“…Metabolite quantification by LC-MS/MS was performed by our BioMS technology platform as previously described 13 .…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dietary methionine/choline deficiency affects behavioural and molecular circadian rhythms

Saer,

Taylor,

Hayes

et al. 2024

Preprint

Self Cite

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“…Antidepressant non-responders (N = 46) showed improved self-report of cognitive function following 6 weeks of adjunct S-Adenosylmethionine treatment [200,201]. Recent metabolomic investigations highlighted the potential of exogenous S-Adenosylmethionine to upregulate toxic metabolite adenine, hindering the clinical practicality of this agent [202].…”

Section: Beyond Primary Neurotransmission -Novel Clinical Targetsmentioning

confidence: 99%

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research

et al. 2022

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Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition.

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“…Unfortunately direct SAMe supplementation has recently been shown to be counterproductive (20). Vitamins B3,9 (folate),12 require methylations (Mg 2+ as cofactor and ATP chelate) to attain active status.…”

Section: Antioxidantsmentioning

confidence: 99%

Antioxidants and Long Covid

Chambers¹

2022

Preprint

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Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these - Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health - is presented.

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Excess S-adenosylmethionine inhibits methylation via catabolism to adenine

Cited by 22 publications

References 83 publications

Dietary methionine/choline deficiency affects behavioural and molecular circadian rhythms

Dietary methionine/choline deficiency affects behavioural and molecular circadian rhythms

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research

Antioxidants and Long Covid

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