Disease relevance of S-adenosylmethionine

• After 10 min of ischemia beta-hydroxypalmitoyl-CoA and beta-hydroxystearoyl-CoA constituted at least 16% of the incremental long-chain acyl-CoA, whereas beta-hydroxypalmitoylcarnitine and b-hydroxystearoylcarnitine constituted 8% of the incremental long-chain acylcarnitine [1].
• Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation [2].
• Biochemical studies revealed hyperlysinemia, hypocarnitinemia, normal organic acid profile, and an unusual acylcarnitine species in both urine and blood [3].
• This retrospective analysis examined the bile acylcarnitine profiles of 27 children with acute liver failure who underwent liver transplantation or died [4].
• Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration [5].

Psychiatry related information on S-adenosylmethionine

• We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls [6].

High impact information on S-adenosylmethionine

• Metabolic profiling of 36 acylcarnitine species by tandem mass spectrometry revealed a unique decrease in the concentration of one lipid-derived metabolite, beta-OH-butyrate, in muscle of MCD-overexpressing animals [7].
• Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state [8].
• Abnormalities are consistent with specific disruption of fatty-acid oxidation caused by impaired entry of long-chain acylcarnitine esters into the mitochondria and failure of the mitochondrial respiratory chain at complex 11 [9].
• Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevated C8-acylcarnitine concentration (> 0.3 microM), a ratio of C8/C10 acylcarnitines of > 5, and lack of elevated species of chain length > C10 [10].
• The incorporation of [14C] arachidonic acid into the phospholipids and acylcarnitine (acyl-Cn) of spur cells and normal RBCs was analyzed by a direct-phase high performance liquid chromatography column to separate both the phospholipids and acyl-Cn [11].

Chemical compound and disease context of S-adenosylmethionine

• This study was carried out to investigate whether administration of high doses of i.v. L-carnitine in patients with acute myocardial infarction could increase urinary excretion of acylcarnitine and reduce early ventricular arrhythmias [12].
• These correlations indicated that the development of fatty liver after partial hepatectomy is due to an increased partitioning of long-chain acyl-CoA towards acylglycerol synthesis and away from acylcarnitine formation [13].
• RESULTS: The elevated creatine kinase and lactate levels with abnormal urine organic acid and acylcarnitine profiles in this patient suggested a mitochondrial disorder [14].
• Using electrospray/tandem mass spectrometry, we analyzed for acylcarnitine postmortem bile specimens from two infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one infant with glutaryl-CoA dehydrogenase deficiency, and 17 uninformative SIDS cases as controls [15].
• Free and acylcarnitine in serum and urine samples were measured in five patients with hyperammonemia associated with anticonvulsant therapy including sodium valproate, of whom three had a Reye-like syndrome [16].

Biological context of S-adenosylmethionine

• The geometry of the SAM and the magnesium binding sites is similar to that found in cathechol O-methyltransferase [17].
• Carnitine supplementation has been hypothesized to improve exercise performance in healthy humans through various mechanisms, including enhanced muscle fatty acid oxidation, altered glucose homeostasis, enhanced acylcarnitine production, modification of training responses, and altered muscle fatigue resistance [18].
• Derivatization is rapid and complete with no evidence of acylcarnitine hydrolysis [19].
• This suggested that the lower degree of ketonaemia observed in meal-fed rats before a meal is not due to the inability of acylcarnitine formation to compete successfully with esterification of fatty acids to the glycerol moiety [20].
• Carnitine and acylcarnitine derivatives have been reported to inhibit cell aggregation (Fritz and Burdzy, 1989, J. Cell. Physiol., 140:18-28) [21].

Anatomical context of S-adenosylmethionine

• The extent of endogenous accumulation of long-chain acylcarnitines in junctional regions of the sarcolemma was assessed in isolated myocytes in which endogenous free, short-chain, and long-chain acylcarnitine pools had been equilibrated with [3H]carnitine [22].
• Conversion of the fatty acyl-CoA to fatty acylcarnitine renders the fatty acid more permeable to the various cellular membranes [23].
• Fibroblast acylcarnitine profiles revealed marked butyrylcarnitine elevation [24].
• Correlation between long-chain acylcarnitine in serum and myocardium after heart transplantation in humans [25].
• These intermediates were not observed when peroxisome-deficient cells from Zellweger patients were incubated with the same compounds, pointing to the involvement of peroxisomes in the formation of these acylcarnitine intermediates [26].

Associations of S-adenosylmethionine with other chemical compounds

• These data indicate that peroxisomal carnitine octanoyltransferase and carnitine acetyltransferase function in vivo in the direction of acylcarnitine formation, and suggest that the concentration of L-carnitine could influence the specificity for different acyl-CoA substrates [27].
• Mitochondria from patients with defects in electron transfer flavoprotein and electron transfer flavoprotein:ubiquinone oxido-reductase are associated with slow flux through beta-oxidation and accumulation of long chain acyl-CoA and acylcarnitine esters [28].
• Three enzymes responsible for the catabolism of LPC are inhibited by either long-chain acylcarnitine or acidic pH [29].
• The hypolipidemic drug clofibrate was an effective in vitro inhibitor of acylcarnitine hydrolase activity but not of acyl-CoA hydrolase activity [30].
• Moreover, the low free carnitine and short-chain and long-chain acylcarnitine plasma levels found in newborn infants after 7 days of total parenteral nutrition did not seem to impair the utilization of infused lipids [31].

Gene context of S-adenosylmethionine

• Import of acylcarnitine into mitochondrial matrix through carnitine/acylcarnitine-translocase (CACT) is fundamental for lipid catabolism [32].
• The introduction of mass spectrometry to analyze blood acylcarnitine profiles has revolutionized the diagnosis of fatty acid oxidation disorders including CPT II deficiency [33].
• Our results demonstrate different tissue-specific long-chain acylcarnitine profiles in response to various stressors, which may be of importance with respect to the heterogeneous clinical manifestations of VLCAD deficiency in humans [34].
• However, the results indicate that Wy-14,643 does not prevent methylation by decreasing either the availability of SAM or the activity of DNA MTase [35].
• Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS) [36].

Analytical, diagnostic and therapeutic context of S-adenosylmethionine

• The concentrations of free, short-chain, and long-chain acylcarnitine were determined in 19 right ventricular endomyocardial biopsies and in serum from 14 patients after orthotopic heart transplantation and 3 nontransplanted control patients with normal cardiac function [25].
• The aliphatic chain distribution of myocardial acylcarnitine molecular species identified by electrospray ionization mass spectroscopy was independently substantiated by sequential HPLC purification and capillary gas chromatography [37].
• Free, acetyl-, medium- and long-chain acylcarnitine and total plasma carnitine concentrations were measured in eight continuous ambulatory peritoneal dialysis (CAPD) patients and eight age- and sex-matched healthy controls [38].
• We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD [39].
• Our study adds a novel method to the diagnosis of PBD, which may also be of benefit for future neonatal mass screening programs based on acylcarnitine profiling [40].

References