Glycine homeostasis requires reverse SHMT flux

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(1), P. 103 - 115.e4

Published: Jan. 1, 2024

Language: Английский

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Gut microbiome signatures of vegan, vegetarian and omnivore diets and associated health outcomes across 21,561 individuals

Nature Microbiology, Journal Year: 2025, Volume and Issue: 10(1), P. 41 - 52

Published: Jan. 6, 2025

Abstract As plant-based diets gain traction, interest in their impacts on the gut microbiome is growing. However, little known about diet-pattern-specific metagenomic profiles across populations. Here we considered 21,561 individuals spanning 5 independent, multinational, human cohorts to map how differences diet pattern (omnivore, vegetarian and vegan) are reflected microbiomes. Microbial distinguished these common patterns well (mean AUC = 0.85). Red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes (for example, Ruminococcus torques , Bilophila wadsworthia Alistipes putredinis ) negatively correlated host cardiometabolic health. Conversely, vegan were favourable markers enriched omnivores consuming more foods. Diet-specific partially overlapped food especially dairy microbes, for Streptococcus thermophilus typical soil vegans. The signatures western can support future nutritional interventions epidemiology.

Language: Английский

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Don’t Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 650 - 650

Published: Jan. 14, 2025

Sphingolipidomic mass spectrometry has provided valuable information-and surprises-about sphingolipid structures, metabolism, and functions in normal biological processes disease. Nonetheless, many noteworthy compounds are not routinely determined, such as the following: most of sphingoid bases that mammals biosynthesize de novo other than sphingosine (and sometimes sphinganine) or acquire from exogenous sources; infrequently considered metabolites bases, N-(methyl)n-derivatives; "ceramides" common N-acylsphingosines; complex sphingolipids sphingomyelins simple glycosphingolipids, including glucosyl- galactosylceramides, which usually reported "monohexosylceramides". These subspecies discussed, well some circumstances when they likely to be seen (or present missed) due experimental conditions can influence uptake diet microbiome, artifacts produced during extraction analysis. If these factors kept mind design interpretation lipidomic studies, investigators surprised by how often appear thereby advance knowledge about them.

Language: Английский

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Blood D-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 192, P. 106413 - 106413

Published: Jan. 20, 2024

We recently described increased D- and l-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, post-mortem caudate-putamen human Parkinson's disease (PD) brains cerebrospinal fluid (CSF) de novo living PD patients. However, data regarding blood levels are scarce. Here, we investigated whether serum profile l-serine, as well other glutamate N-methyl-d-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between patients healthy controls (HC) (ii) correlates with clinical-demographic features levodopa equivalent daily dose (LEDD) PD. Eighty-three consecutive forty-one HC were enrolled. cohort underwent an extensive clinical characterization. Serum L-glutamate, l-glutamine, l-aspartate, L-asparagine glycine determined using High Performance Liquid Chromatography. In age- sex-adjusted analyses, no differences emerged d-serine, NMDAR-related acids HC. found that d-serine D−/Total serine ratio positively correlated age but not HC, also at onset. Moreover, higher LEDD lower excitatory acids. Following these results, addition covariate analyses disclosed a selective significant increase compared to (Δ ≈ 38%). Overall, findings suggest may represent valuable biochemical signature

Language: Английский

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Arginine: at the crossroads of nitrogen metabolism

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Abstract L-arginine is the most nitrogen-rich amino acid, acting as a key precursor for synthesis of nitrogen-containing metabolites and an essential intermediate in clearance excess nitrogen. Arginine’s side chain possesses guanidino group which has unique biochemical properties, plays primary role nitrogen excretion (urea), cellular signaling (nitric oxide) energy buffering (phosphocreatine). The post-translational modification protein-incorporated arginine by guanidino-group methylation also contributes to epigenetic gene control. Most human cells do not synthesize sufficient meet demand are dependent on exogenous arginine. Thus, dietary important maintaining health, particularly upon physiologic stress. How adapt changes extracellular availability unclear, mostly because nearly all tissue culture media supplemented with supraphysiologic levels Evidence emerging that arginine-deficiency can influence disease progression. Here, we review new insights into importance metabolite, emphasizing central mitochondria synthesis/catabolism recent discovery act molecule regulating expression organelle dynamics.

Language: Английский

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Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycle

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 8, 2025

During mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses preserve cellular health. One such pathway integrated stress response (mtISR), which known be activated by DNA (mtDNA) damage. However, causal molecular signals responsible for activation of mtISR remain mostly unknown. A gene often associated with mtDNA mutations/deletions Polg1, encodes Polymerase γ (PolG). Here, we describe an inducible, tissue specific model PolG mutation, in muscle animals leads rapid development dysfunction muscular degeneration male from ~5 months age. Detailed profiling demonstrated robust muscles these animals. This was accompanied striking alterations enzymes folate cycle that likely driven a depletion metabolite 5,10 methenyl-THF, strongly implying imbalanced intermediates as previously unrecognised pathology linking disease. Bond et al. show inducible mutation causes damage wasting. (ISR) reduction intermediates, impaired metabolism ISR/disease induction.

Language: Английский

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Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 9, 2024

Frailty is a common age-related clinical syndrome characterized by decline in the function of multiple organ systems, increased vulnerability to stressors, and huge socio-economic burden. Despite recent research efforts, physiopathological mechanisms underlying frailty remain elusive biomarkers able predate its occurrence early stages are still lacking. Beyond physical component, cognitive represents critical domain associated with higher risk adverse health outcomes. We measured High-Performance Liquid Chromatography (HPLC) pool serum amino acids including L-glutamate, L-aspartate, glycine, D-serine, as well their precursors L-glutamine, L-asparagine, L-serine cohort elderly subjects encompassing entire continuum from fitness frailty. These known orchestrate excitatory inhibitory neurotransmission, turn, play key role intermediates energy homeostasis liver, kidney, muscle, immune system metabolism. To comprehensively assess frailty, we employed both Edmonton Frail Scale (EFS), practical tool capture multidimensionality phenotype, measure function. found that D-serine D-/Total serine ratio were independent predictors EFS but not Furthermore, levels glycine/L-serine worse cognition depressive symptoms frail group. findings suggest changes peripheral glycine enantiomers may represent novel biochemical correlate

Language: Английский

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Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(10), P. 1484 - 1500.e9

Published: Aug. 23, 2024

Language: Английский

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Urinary metabolomics signature of animal and plant protein intake and its association with 24-h blood pressure: the African-PREDICT study

Hypertension Research, Journal Year: 2024, Volume and Issue: 47(9), P. 2456 - 2470

Published: July 4, 2024

Abstract The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat fibre) amino acid (AA) compositions. This study determined whether were related metabolomic profiles associated BP. included 1008 adults from African-PREDICT (aged 20–30 years). Protein was using 24-h dietary recalls. Twenty-four-hour ambulatory BP measured. Amino acids acylcarnitines analysed in spot urine samples liquid chromatography-tandem mass spectrometry-based metabolomics. Participants a low plant, high had higher SBP (by 3 mmHg, p = 0.011) than those (low-risk group). We found that mediated by BMI intake, which independently SBP. therefore not multiple regression analysis after adjusting for confounders. In low-risk group, methionine (Std. β −0.217; 0.034), glutamic −0.220; 0.031), glycine −0.234; 0.025), proline −0.266; 0.010) inversely SBP, beta-alanine −0.277; 0.020) DBP. Ultimately diet contribute means increased intake. Conversely, levels urinary AAs observed consuming rich lower

Language: Английский

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Serine and glycine physiology reversibly modulate retinal and peripheral nerve function

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(10), P. 2315 - 2328.e6

Published: Aug. 26, 2024

Metabolic homeostasis is maintained by redundant pathways to ensure adequate nutrient supply during fasting and other stresses. These are regulated locally in tissues systemically via the liver, kidney, circulation. Here, we characterize how serine, glycine, one-carbon (SGOC) metabolism fluxes across eye, kidney sustain retinal amino acid levels function. Individuals with macular telangiectasia (MacTel), an age-related disease reduced circulating serine carrying deleterious alleles SGOC metabolic enzymes exhibit exaggerated reduction serine. A Phgdh

Language: Английский

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