Urine suberic acid

As a result of GC-MS analyses, 103 metabolites were determined, of which 66 were successfully identified and 18 were used to create a diagnostic model. Of these 18 metabolites, 5 (suberic acid, glycine, L-tyrosine, L-threonine, and succinic acid) had significantly higher levels in patients with HCC than in healthy volunteers (p < 0.05). Other metabolites (oxalic acid, xylitol, urea, phosphates, propanoic acid, threonine, pimelic acid, butyric acid, trihydroxypentanoic acid, hypoxanthine, arabinofuranose, dipeptide of hydroxyproline, and tetrahydroxypentanoic acid) showed higher levels in healthy volunteers (p < 0.05). In addition, Wu et al. determined the levels of AFP using an ELISA test in serum from the same patients and healthy volunteers as in the metabolomic study of urine samples. An AFP concentration above 20 ng/mL suggests a positive result and the presence of... 

In known metabolic states and disorders, the nature of metabolites excreted at abnormal levels has been identified by GC-MS. Examples of this are adipic and suberic acids found in urine from ketotic patients [347], 2-hydroxybutyric acid from patients with lactic acidosis [348], and methylcitric acid (2-hydroxybutan-l,2,3-tricarboxylic acid) [349] in a case of propionic acidemia [350,351]. In the latter instance, the methylcitric acid is thought to be due to the condensation of accumulated propionyl CoA with oxaloacetate [349]. Increased amounts of odd-numbered fatty acids present in the tissues of these patients due to the involvement of the propionyl CoA in fatty acid synthesis, have also been characterised [278]. A deficiency in a-methylacetoacetyl CoA thiolase enzyme in the isoleucine pathway prevents the conversion of a-methylacetoacetyl CoA to propionyl CoA and acetyl CoA [352,353]. The resultant urinary excretion of large amounts of 2-hydroxy-3-methylbutanoic acid (a-methyl-/3-hydroxybutyric acid) and an excess of a-methylacetoacetate and often tiglyl glycine are readily detected and identified by GC-MS. 

Lofata Burne was excreting dicarboxylic acids in her urine, particularly adipic acid (which has 6 carbons) and suberic acid (which has 8 carbons). 

This chapter describes the case reports of these enzyme deficiencies and the underlying biochemistry of the disorders and their associations. It is not the intention to discuss keto acidosis associated with other diseases, for example juvenile diabetes, or ketogenesis and its control which are reviewed elsewhere (Wildenhoff, 1975, 1977 McGarry and Foster, 1976 Halperin, 1977). In addition to the common occurrence of 3-hydroxybutyrate and acetoacetate in body fluids of patients with keto acidosis, secondary organic acids have been observed in urine, including adipic and suberic acids (Pettersen et aL, 1972), 3-hydroxyisovaleric acid (Landaas, 1974), 3-hydroxyisobutyric acid and 2-methyl-3-hydroxybutyric acid (Landaas, 1975). The dicarboxylic acids occur as a result of initial co-oxidation of accumulating long-chain fatty acids followed by )8-oxidation (Pettersen, 1972), and metabolites of the branched-chain amino acids occur because of inhibition of their metabolic pathways by 3-hydroxybutyrate and acetoacetate (Landaas and Jakobs, 1977). 

Pettersen, J.E., Jellum, E. and Eldjarn, L. (1972), The occurrence of adipic and suberic acid in urine from ketotic patients. Clin. Chim. Acta, 38,17. 

Fig. 14.5 Chromatogram of organic acids extracted using diethyl ether and ethyl acetate from the urine of a patient with suberylglycinuria and separated as their methyl derivatives (diazomethane) on 3 per cent SE-30 on Chromosorb W (DMCS, 80-100 mesh) using temperature programming from 80°C to 250°C at 6°C min Peak identifications are 1, 3-hydroxybutyrate 2, adipate 3, 3-methyladipate 4, pimelate (heptanedioate) 5, octenedioate 6, suberate (octanedioate) 7, hexanoylglycine plus 4-hydroxyphenylacetate 8, azeleate (nonanedioate) 9, decenedioate 10, sebacate (decanedioate) 11, hippurate 12, unknown, 13, suberylglycine. (Redrawn with modifications from Truscott et al., 1979)...

Fig. 14.7 Chromatogram of organic acids extracted using ethyl acetate and diethyl ether from the urine of a child with Jamaican vomiting sickness, separated as their methyl derivatives (diazomethane) on 5 per cent OV-1 using temperature programming from 70°C to 300°C at 4°C min with a 4 min initial isothermal delay. Peak identifications are 1, 3-hydroxybutyrate plus 3-hydroxyisovalerate (approx. 4 6) 2, ethylmalonate 3, methylsuccinate 4, octanoate 5, glutarate 6, adipate 7, isovalerylglycine 8, 4-octenedioate plus furandicarboxylate 9, suberate (octanedioate) 10, /i-hexanoyl-glycine 11, decenedioate 12, sebacate (decanedioate) 13, hippurate 14, n-pentadecanoate (internal standard) 15, palmitate 16, stearate. (Redrawn with modifications from Tanaka et al, 1976)...

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