Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function

Biomolecules, Год журнала: 2025, Номер 15(2), С. 216 - 216

Опубликована: Фев. 2, 2025

Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups between acetyl-CoA and carnitine. This enzymatic activity ensures optimal functioning carbon flux preventing accumulation, buffering flexibility, regulating balance fatty acid glucose oxidation. CRAT’s interplay with carnitine shuttle, involving palmitoyltransferases (CPT1 CPT2) carrier (SLC25A20), underscores its critical role energy metabolism. Emerging evidence highlights structural functional diversity CRAT structurally related acetyltransferases across cellular compartments, illustrating their coordinated lipid metabolism, amino catabolism, bioenergetics. Moreover, insights into have paved way for understanding regulation identifying potential modulators therapeutic applications diseases such as diabetes, disorders, cancer. review examines aspects, relationships shuttle members other acyltransferases, broader health disease. The targeting associated pathways offers promising avenues interventions aimed at restoring equilibrium addressing dysfunction disease states.

Язык: Английский

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The Lower Concentration of Plasma Acetyl-Carnitine in Epicardial Artery Disease—A Preliminary Report

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1318 - 1318

Опубликована: Фев. 4, 2025

Coronary artery disease remains an epidemiological challenge as global morbidity is not declining despite the fact that risk factors are well known. Metabolomic derivatives of atherosclerosis formation have recently gained attention a possible non-traditional factor. The aim this study was to find potential differences in acetyl-carnitine chain serum concentrations between epicardial patients and control group. There were 41 (25 men 16 women), with median (Q1–Q3) age 69 (63–73) years, enrolled prospective metabolomic analysis. They divided into two groups based on cine angiography results confirming (group 1, n = 25 (61%)) or showing characteristics corresponding normal angiograms 2, (39%)). quantitation metabolites performed coronary angiograms. Significant related plasma concentration L-Acetyl-carnitine (7.49 (4.79–9.23) µM vs. 9.36 (8.57–10.23) (p 0.009)), Decanoyl-carnitine (0.00 (0.00–0.37) 0.36 (0.19–0.44) 0.040)), C12:1-carnitine (0.17 (0.14–0.20) 0.22 (0.18–0.24) 0.008)), trans-2-Dodecenoyl-carnitine (0.10 (0.07–0.13) 0.13 (0.10–0.15) 0.002)), cis-5-Tetradecenoyl-carnitine (0.03 (0.02–0.04) 0.04 (0.03–0.05) 0.043)), 3,5-Tetradecadien-carnitine (0.16 (0.14–0.18) 0.18 (0.17–0.27) 0.007)) group 1 2 noted. Increased levels may be characteristic

Язык: Английский

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Acylcarnitine Profiling in Meningiomas with Different NF2 Mutation Statuses

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1570 - 1570

Опубликована: Фев. 13, 2025

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it related to loss of a suppressing protein called merlin. At same time, alterations energy production are visible cancer cells, where increased demands for observed. Fatty acid oxidation could be one ways cells obtain energy. This metabolic pathway uses acylcarnitine shuttle system, which responsible acylation fatty acids their transport through mitochondria. Therefore, this study aimed profile acylcarnitines short, medium, long acyl chain lengths meningiomas assess changes tumors different statuses. For analysis, solid-phase microextraction (SPME) coupled liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was used. presented sampling method enabled less invasive easy collection analytes from studied lesions, can crucial future analysis potential biomarkers surgery room. It observed that higher levels these characterized mutations. Moreover, consumption elevated show considered markers mutated cells.

Язык: Английский

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Temporal and Inter-animal Variation in Bloodspot Acylcarnitine and Amino Acid Profiles in Relation to Conventional Metabolites and Hormones in Holstein Dairy Cows

Journal of Dairy Science, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The transition from late gestation to early lactation in dairy cows involves dynamic metabolic adaptations orchestrated by homeorhetic mechanisms, including hepatic fatty acid and amino metabolism. To gain deeper understanding of these we evaluated changes bloodspot acylcarnitines (AC) free (AA) profiles, conventional blood biomarkers energy balance [β-hydroxybutyrate (BHB), nonesterified acids (NEFA), glucose, insulin, insulin-like growth factor-1 (IGF-1), fructosamine) along with weekly milk composition dry matter intake 2 sequential observational trials. Data were analyzed using correlation cluster analysis, linear-mixed effects models without repeated measures. Study 1, which involved 28 multiparous Holstein-Friesian sampled 7 d before calving at 3, 6, 9 21 after calving, revealed strong positive correlations between glycine-to-alanine ratio BHB (r = 0.58) NEFA 0.59), though weakened study 2. Four trajectory patterns AC, AA, metabolite ratios identified. Group 1 (e.g., C5, C16, C18) showed transient postpartum increase peaking 3 or returning prepartum levels 21. tyrosine, C0:(C16 + exhibited decrease, normalizing C4DC:C3, t[AC]:C0, valine-to-phenylalanine ratio) displayed variable responses, while group 4 persistent differences 21, elevated valine-to-leucine but reduced methionine ornithine-to-citrulline compared levels. 2, examined inter-cow variations comprised 74 (83 lactations) milk, distinct clusters clinically healthy based on longitudinal time serum profiles: "Normal" "High yield -hyperketonemia (HMY-HYK)." HMY-HYK had higher (41.6 ± 1.05 vs. 39.4 0.767 kg/d), average (0.996 0.086 0.754 0.062 mmol/L 0.498 0.051 0.534 0.071 mmol/L, respectively) lower insulin (0.343 0.030 0.368 0.041ng/mL) the 'Normal' cluster. yield, increased urea concentrations, citrulline suggest enhanced AA catabolism for gluconeogenesis activity ornithine-citrulline cycle. Elevated malonylcarnitine (C3DC), long-chain AC (LCAC) C16 C18 carbon chains, acetylcarnitine-to-free carnitine (C2:C0) (C0) indicate efficient mitochondrial potentially exporting acyl-CoA as C2 LCAC mitigate stress associated NEFA. In conclusion, highlight time-dependent inter-animal shifts adipose muscle mobilization well adaptive metabolism support thus synthesis lactation.

Язык: Английский

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KRAS G12V mutation-selective requirement for ACSS2 in colorectal adenoma formation

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115444 - 115444

Опубликована: Март 24, 2025

Язык: Английский

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