3-Methyladipic acid

Organic acids or urine in multiple sclerosis

The urinary excretion of organic acids was examined in 509 cases with multiple sclerosis and in 50 age- and sex-matched controls. The concentrations of the acids were related to creatinine. No differences were found for compounds such as glycolic acid, 2-methyl-3-hydroxybutyric acid, 2-ethylhydracrylic acid, 4-hydroxyphenylacetic acid, suberic acid and many other acids. However, the mean excretion of 2-hydroxy-2-methyl-3-butenoic acid was increased two-fold in the MS group. 2 MS cases had a very high excretion of 3-methylglutaconic acid, and another 6 cases had moderate elevations, which were fairly constant over a time period of several months. Moderate elevations were also noted in 2 healthy controls. 1 MS case had a very high excretion of 3-hydroxyisovaleric acid. 7 MS cases, and none in the control group, had elevated excretion of adipic acid. Differences were also noted for lactic acid, succinic acid, aconitic acid and 3-methyladipic acid. An oral dose of deuterium-labelled acetate was given to one of the patients with high excretion of 3-methylglutaconic acid. Deuterium was incorporated into this metabolite. 3-methylglutaconic acid, 2-hydroxy-2-methyl-3-butenoic acid, 3-hydroxy-isovaleric acid and 3-methyladipic acid are all potential isoprenoid metabolites. A possible defect in the pathway of isoprenoid biosynthesis is discussed.

Ammonium fluoride as a mobile phase additive in aqueous normal phase chromatography

The use of ammonium fluoride as a mobile phase additive in aqueous normal phase chromatography with silica hydride-based stationary phases and mass spectrometry detection is evaluated. Retention times, peak shape, efficiency and peak intensity are compared to the more standard additives formic acid and ammonium formate. The test solutes were NAD, 3-hydroxyglutaric acid, α-ketoglutaric acid, p-aminohippuric acid, AMP, ATP, aconitic acid, threonine, N-acetyl carnitine, and 3-methyladipic acid. The column parameters are assessed in both the positive and negative ion detection modes. Ammonium fluoride is potentially an aggressive mobile phase additive that could have detrimental effects on column lifetime. Column reproducibility is measured and the effects of switching between different additives are also tested.

Supramolecular helical mesomorphic polymers. Chiral induction through H-bonding

The work described here concerns a challenge of general interest in supramolecular chemistry: the achievement of chiral helical organizations with controlled structures. This work provides a strategy to obtain supramolecular polymers in which a chiral helical conformation has been induced by a noncovalent association, that is, through hydrogen bonding. Polycatenar 2,4,6-triarylamino-1,3,5-triazines, which organize into columnar mesophases and are susceptible to H-bonding interactions, were chosen as a starting point to build up the chiral supramolecular structure. The stacking of these mesogens has been forced to wind in a helical way by means of H-bond association with (R)-3-methyladipic acid, within the mesophase. The optically active columnar organization has been studied in depth by optical microscopy, differential scanning calorimetry (DSC), X-ray diffraction, and circular dichroism. Formation of stable complexes between the triazine units and (R)-3-methyladipic acid has also been investigated by means of NMR diffusion-ordered spectroscopy (DOSY) experiments in chloroform.

Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease

Adult Refsum disease (ARD) is associated with defective alpha-oxidation of phytanic acid (PA). omega-Oxidation of PA to 3-methyl-adipic acid (3-MAA) occurs although its clinical significance is unclear. In a 40 day study of a new ARD patient, where the plasma half-life of PA was 22.4 days, omega-oxidation accounted for 30% initially and later all PA excretion. Plasma and adipose tissue PA and 3-MAA excretion were measured in a cross-sectional study of 11 patients. The capacity of the omega-oxidation pathway was 6.9 (2.8-19.4) mg [20.4 (8.3-57.4) micromol] PA/day. 3-MAA excretion correlated with plasma PA levels (r = 0.61; P = 0.03) but not adipose tissue PA content. omega-Oxidation during a 56 h fast was studied in five patients. 3-MAA excretion increased by 208 +/- 58% in parallel with the 158 (125-603)% rise in plasma PA. Plasma PA doubled every 29 h, while 3-MAA excretion followed second-order kinetics. Acute sequelae of ARD were noted in three patients (60%) after fasting. The omega-oxidation pathway can metabolise PA ingested by patients with ARD, but this activity is dependent on plasma PA concentration. omega-Oxidation forms a functional reserve capacity that enables patients with ARD undergoing acute stress to cope with limited increases in plasma PA levels.

Pattern of aliphatic dicarboxylic acids in uremic serum including a new organic acid, 2,4-dimethyladipic acid

(1) 2,4-Dimethyladipic acid was first identified in normal human urine using gas chromatography-mass spectrometry. Urinary excretion of 2,4-dimethyladipic acid in 7 healthy adults ranged from 4.9 mumol to 14 mumol per 24 h. (2) Succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were identified in the ultrafiltrate of the blood obtained from a chronic uremic patient using a hemodialyzer. (3) Levels of succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid in uremic serum were determined using a mass fragmentographic technique. Concentration of succinic acid in uremic serum was comparable to that in normal serum, whereas concentrations of adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were highly elevated in uremic serum.