Micronutrient Supplementation and Ergogenesis — Metabolic Intermediates
Luke Bucci in Nutrients as Ergogenic Aids for Sports and Exercise, 2020
A study of 30 males and 20 females (well-trained) at the Sports Polyclinic in Bucharest, Romania, given 3 g/d carnitine for 21 d found significant increases in VO2max (11%), less blood lactate levels after exercise (7.9 vs. 9.9 mM) and lower plasma triglyceride levels.926 Acute, intravenous administration of 1 g L-carnitine 60 min before exercise to 17 elite swimmers at the Sports Polyclinic in Bucharest in a double-blind, crossover trial was associated with significant changes compared to the placebo period in post-exercise values of plasma lactate, triglycerides, free fatty acids, and evoked muscular potential.927 A series of 6 double-blind, placebo-controlled, randomized crossover trials at the Sports Polyclinic in Bucharest was conducted with 110 elite athletes (swimmers, rowers, canoers, weight lifters, and long-distance runners) to study effects on physiological parameters of carnitine supplementation.928 Both acute, single doses of 1 g carnitine and daily doses of 1 to 3 g of carnitine for 3 weeks were administered. Significant changes after both acute and chronic carnitine administration, compared to placebo periods, were seen for post-exercise plasma lactate, triglycerides, free fatty acids, and evoked muscular potential. Changes in plasma and urine carnitine metabolites indicated increased free carnitine and post-exercise acetylcarnitine levels during supplemented periods. Results of this series of studies agree with the hypothesis that increased levels of free carnitine allow greater amounts of fatty acids to be utilized as an energy source during intense exercise.
Carnitine-acylcarnitine translocase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Dynamic acetylation and deacetylation of nuclear histones is essential for regulating the access of chromosomal DNA to transcriptional machinery. The source of acetylCoA for histone acetylation in mammalian cell nuclei is not clear. Acetylcarnitine formed in mitochondria is transported into cytosol by carnitine/acylcarnitine translocase, and then enters the nucleus, where it is converted to acetylCoA by a nuclear carnitine acetyltransferase and becomes a source of acetyl groups for histone acetylation. Genetic deficiency of the translocase markedly reduced the mitochondrial acetylcarnitine-dependent nuclear histone acetylation, indicating the significance of the carnitine-dependent mitochondrial acetyl group contribution to histone acetylation [39].
Hepatic Encephalopathy
Charles Theisler in Adjuvant Medical Care, 2023
Carnitine: Although the mechanisms by which carnitine provides neurological protection are unknown, a systematic review of the literature confirmed that L-acetylcarnitine is promising as a safe and effective treatment for HE.3,4 L-carnitine or a placebo was administered to 120 patients with hepatic encephalopathy for 60 days. Fasting serum ammonia levels were significantly lower at 30 and 60 days compared to baseline and placebo. Mental function was also significantly improved by L-carnitine in cirrhotic patients.5
Logistic role of carnitine shuttle system on radiation-induced L-carnitine and acylcarnitines alteration
Published in International Journal of Radiation Biology, 2022
CrAT is highly enriched in muscle and heart and localized to the mitochondrial matrix (Figure 2). This enzyme converts excess acetyl-CoAs to acetylcarnitine, facilitating the export of acetyl-CoA from mitochondrial to the cytosol and buffering the pools of intracellular acetyl-CoA (Muoio et al. 2012). Acetylcarnitine in blood and tissues has emerged as a biomarker of energy surplus (Seiler et al. 2015). The intermediates of the TCA cycle and the activity of the TCA cycle were decreased after irradiation (Tyburski et al. 2008; Akpolat et al. 2013; Pannkuk et al. 2019b). The elevation of acetyl-CoA might reflect the inhibition of TCA by radiation. CrAT deficiency leads to accumulating acetyl-CoA, which may further affect the activity of CACT, finally alters the L-carnitine and acylcarnitines profiles.
Precision medicine for the treatment of sepsis: recent advances and future prospects
Published in Expert Review of Precision Medicine and Drug Development, 2019
Omics is a growing field of research that encompasses the structural and functional study of genes, gene expression, metabolites, and proteins and their dynamics in the organism [12]. Study of the metabolome in patients with sepsis attempts to identify characteristic profiles of cellular function in response to disease. Short-chain acylcarnitines, metabolites involved in mitochondrial fatty acid β-oxidation, showed prognostic correlations in a prospective study of 210 patients with sepsis admitted to ICUs at two medical centers [24]. Patients with high plasma acetylcarnitine had significantly higher 28-day mortality than those with lower plasma levels (52.6% vs. 13.9%); furthermore, high acetylcarnitine levels were associated with blood culture positivity and showed a positive correlation with various cytokines, such as interleukin (IL)-6, IL-8, and IL-10 [24]. Early changes in molecules involved in the lipid, energy, and protein metabolisms have also demonstrated prognostic ability in patients with septic shock. Low levels of long-chain polyunsaturated fatty acids, which have suppressive effects in T-cell activation, were associated with 90-day mortality [25]; together with lysophosphatidylcholines, they were also significantly lower in patients which did not respond to treatment during the first 48 hours of ICU admission [26]. Kynurenine, a protein involved in tryptophan catabolism, correlated positively with 28-day and 90-day mortality [25]. Increased levels of alanine were associated with no-response to treatment, which may reflect the impairment in gluconeogenesis due to liver dysfunction in shock [26].
Metabolomics reveals the depletion of intracellular metabolites in HepG2 cells after treatment with gold nanoparticles
Published in Nanotoxicology, 2018
Jeremie Zander Lindeque, Alnari Matthyser, Shayne Mason, Roan Louw, Cornelius Johannes Francois Taute
Internal standard and stable isotope solution were added to each of the cell samples, to a final concentration of 50 μg/ml. The solution consisted of 3-phenylbutyric acid, norleucine, 2-acetamidophenol, and stable isotopes of arginine, citrulline, glycine, lysine, glutamic acid, phenylalanine, isoleucine, methionine, valine, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, tetradecanoylcarnitine, hexadecanoylcarnitine, and octadecanoylcarnitine. A pellet size amount of glass beads (Restch, 22.222.0002) were added to the mixture after which the tubes were shaken vigorously at 30 Hz for 5 min using a M400 vibration mill (Retsch). After homogenization of the cells, 660 µl chloroform was added and mixed sufficiently. The samples were allowed to stand on ice for 20 min after which they were centrifuged at 2930 × g for 20 min. The top aqueous phase and bottom organic layer were aspirated into a clean 2 ml GC-MS vial (Agilent) without disrupting the interphase consisting of cell debris and precipitated proteins. One third of each sample was then transferred to a separate vial for LC-MS/MS analysis of acylcarnitines and amino acids. The samples were dried under nitrogen at 37 °C.
Related Knowledge Centers
- Acetylation
- Acyl Group
- Coenzyme A
- Esterase
- Carnitine
- Citric Acid Cycle
- Blood Plasma
- Mitochondrion
- Nutrient
- Acetyl-Coa