Urine glutaric acid

S. Glutaric Acid. Glutaric acid has been found by paper chromatography to be a regular constituent of normal human urine (N20, 05). 

The urinary elimination of glutaric acid increases in rats after administration of L-lysine (T15), a fact which is in accordance with the known metabolic route leading from lysine to glutaric acid via pipecolic acid (R8) (Fig. 5). Another intermediate of that metabolic sequence, a-keto-adipic acid, is foimd in urine after administration of lysine to the rat, the amount representing about 2 % of that of the administered L-lysine... 

C4). Boulanger and Osteux (B28) found, however, that in steriUzed rats pipecolic acid is the only radioactive compound found in the urine after injection of labeled pipecolic acid, so that this acid does not appear to be transformed rapidly into glutaric acid. 

Another possible source of glutaric acid might be tryptophan, since Gholson et al. (GIO) have shown that administration of labeled tryptophan to rats is followed by excretion of labeled glutaric acid in urine. 

Adipic Acid. Adipic acid was first shown in normal urine during paper chromatographic studies (N13) the daily normal elimination lies between 1.3 and 2.5 mg (T18) but increases after administration of e-aminocaproic acid, a part of which would be transformed into adipic acid by oxidative deamination (T18). After administration of adipic acid, one finds a larger amount in the urine than when administering glutaric acid (W8). 

Methylsuccinic Acid. Methylsuccinic acid has been shown to be present in normal urine in about the same amount as glutaric acid (T15). It increases after administration of leucine. 

Table 18.1 Known causes of glutaric acid elevations in plasma or urine...

GA-1 results in the accumulation of 3-hydroxyglutaric acid and glutaric acid in the urine [1,2], the metabolites most likely associated with the risk of neurological damage (Box 19.1). 

Elevated blood, urine, and CSF glutaric acid and 3-OH-glutaric acid, metabolic acidosis... 

Elevated blood, urine, and CSF glutaric acid and 2-OH-glutaric acid, metabolic acidosis, hyperammonemia, hypoglycemia ( ketones), impaired fatty add oxidation Elevated blood, urine, and CSF isovaleric acid metabolic acidosis, hyperammonemia, hypoglycemia... 

Glutaric acid occurs in plant and animal tissues and is found in the blood and urine. Ketoglutaric acid, found as an intermediate in the Krebs cycle, is used in dietary supplements to improve protein synthesis. ... 

Rothstein and Miller (162) isolated radioactive glutaric acid from the urine of rats injected with L-lysine-6-C and unlabeled glutarate and established its chemical and radioactive purity. 

Biotinidase deficiency Folinic acid-responsive seizures Glutaric aciduria type 1 Homocystinuria HyperphenyManinemia due to disorders of biopterin Methylmalonic aciduria Maple syrup urine disease (MSUD) Multiple carboxylase deficiency OAT... 

Manipulation of amino acids in the diet to impact uptake across the blood-brain barrier has been used in patients with maple syrup urine disease [41, 42] and glutaric acidemia [42], A review of LNAA supplementation [43] points out that advances in diets for inherited metabolic diseases will include targeting the concentrations of amino acids in the brain. 

They are defects in the degradation pathways of leucine, isoleucine, and valine. These conditions are usually diagnosed by examining organic acids in urine with abnormal metabolites also notable on acylcamitine profile. Organic acidemias comprise a variety of disorders and include methylmalonic acidemia (MMA), propionic acidemia (PROP), isovaleric acidemia (IVA), glutaric acidemia type 1 (GA-1), 3-methylcrotonyl carboxylase deficiency (3-MCC), 3-methylglutaconic acidemia (3-MGA), and vitamin B12 uptake, transport, and synthesis defects. 

Fig. 7.2 Chromatogram of acidic metabolites extracted from the urine of a normal child using DEAE-Sephadex and re-extraction with solvents after ethoxime formation and freeze-drying by reconstitution in water, acidification with hydrochloric acid, saturation with sodium chloride, and solvent extraction with diethyl ether (three times) and ethyl acetate (three times), evaporation of the solvents from the combined extracts using dry nitrogen and trimethylsilylation using the minimum quantity of BSTFA. Separated on 10 per cent OV-101 on HP Chromosorb W (80-100 mesh) by temperature programming from 110°C to 285°C at 4°C min with an initial 5 min isothermal delay. Peak identifications are 1, phenol plus lactate 2, glycollate 3, cresol 4, 3-hydroxyisovalerate 5, benzoate 6, phosphate 7, succinate 8, 3-methyladipate 9, 3-hydroxy-3-methyl-glutarate 10, 4-hydroxyphenylacetate 11, homovanillate plus some aconitate 12, hippurate 13, citrate 14, vanilmandelate 15, n-tetracosane (standard) 16, n-hexacosane (standard).

Fig. 10.19 Chromatogram of organic acids extracted using ethyl acetate from the urine of a patient with 3-hydroxy-3-methylglutaric aciduria and separated as their trimethylsilyl derivatives on 5 per cent SE 52 on Chromosorb W (AW-DMCS, 100-120 mesh) using temperature programming from 75°C to 220°C at 2°C min with initial and final isothermal delays of 10 min. Peak identifications are 1, 3-hydroxyisovalerate 2, hydroxycaproate isomer 3, glutarate 4, 3-methylglutarate 5 and 6, 3-methyl-glutaconate peaks 7, adipate 8, 4-phenylbutyrate (internal standard) 9, 3-hydroxy-3-methylglutarate 10, ascorbate. (Redrawn with modifications from Duran ct. a/., 1978)...

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