Disease relevance of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• Four had concomitant hypoglycemia, and all had hypoketonemia, with excessive urinary excretion of medium-chain dicarboxylic acids, medium-chain (omega-1)-hydroxyacids, suberylglycine, hexanoylglycine, and octanoylcarnitine [1].

High impact information on (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• Distribution of radiolabel from free [14C]carnitine into acetylcarnitine, isobutyrylcarnitine, and octanoylcarnitine during the incubations was examined by thin layer chromatography and was negligible [2].
• Addition of carnitine was found to increase the export from the mitochondria of acylcarnitines derived from 4-methyl-2-oxopentanoate in the presence of absence of 4-pentenoate but not in the presence of octanoylcarnitine [3].
• The hydrolysis is monitored and calibrated with standard solutions containing octanoylcarnitine [4].
• The reconstituted system catalyzed exchange diffusion of carnitine, exhibited the expected inhibitor and temperature sensitivity, and discriminated between stereoisomers of octanoylcarnitine [5].
• Liver mitochondria from foetal and newborn animals were unable to synthesize ketone bodies from octanoate, but octanoylcarnitine and palmitoylcarnitine were readily ketogenic [6].

Biological context of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• Medium-chain acyl-CoA dehydrogenase deficiency is the most common of the additional diseases being detected and it seems that octanoylcarnitine in blood is a particularly sensitive indicator: some of the cases detected by screening have genotypes suggesting a relatively low risk of serious metabolic decompensation [7].

Anatomical context of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• The diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was suggested by abnormal acylcarnitine profile with increased octanoylcarnitine in the blood, and confirmed by fatty acid oxidation studies and mutation analysis in skin fibroblast cultures [8].
• The analysis of the cord blood sample showed a high concentration of octanoylcarnitine of 2.3 micromol/L (reference <0.1), suggesting a possible fatty acid oxidation disorder [9].

Associations of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium with other chemical compounds

• These acylcarnitines have been examined using fast atom bombardment mass spectrometry in some of these diseases and have been shown to be propionylcarnitine in methylmalonic aciduria and propionic acidemia, isovalerylcarnitine in isovaleric acidemia, and hexanoylcarnitine and octanoylcarnitine in medium-chain acyl-CoA dehydrogenase deficiency [10].
• Acylcarnitine analysis by fast atom bombardment mass spectrometry (FAB-MS) was inconclusive, but FAB-MS/MS (tandem mass spectrometry) revealed diagnostic amounts of octanoylcarnitine and hexanoylcarnitine [11].
• Patients belonging to the first group accumulate octanoate, decanoate and cis-4-decenoate in their plasma; they excrete hexanoylglycine, octanoylcarnitine and suberylglycine in addition to the usual C6-C10 dicarboxylic acids [12].
• The octanoylcarnitine (C8)-to-decanoylcarnitine (C10) and C8-to-acetylcarnitine (C2) ratios were the most specific markers to differentiate mild and classical forms of MCAD deficiency in fibroblasts [13].

Gene context of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine [14].
• The ratios of octanoylcarnitine to decanoyl- or decenoylcarnitine appear specific for MCAD deficiency [15].

Analytical, diagnostic and therapeutic context of (3-carboxy-2-octanoyloxy-propyl)-trimethyl-ammonium

• To obtain data on these issues, we did a retrospective study in which we analysed the concentrations of acylcarnitines in stored neonatal blood spots, and reviewed patients with high octanoylcarnitine concentrations at age 7-9 years [16].

References