The absolute configuration of β-aminoisobutyric acid formed by degradation of thymine in man

Solem, Eivind

doi:10.1016/0009-8981(74)90097-7

Cited by 21 publications

(8 citation statements)

References 11 publications

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“…The concentration of β-AIB is normally low in urine as β-AIB is further catabolized by β-aminoisobutyrate aminotransferases to methylmalonic acid semialdehyde and propionyl-CoA. β-AIB occurs in two isomeric forms and both enantiomers of β-AIB can be detected in human urine and plasma [9][10][11][12]. In plasma, the S-enantiomer is the predominant type due to active renal reabsorption [11].…”

Section: Introductionmentioning

confidence: 99%

“…In plasma, the S-enantiomer is the predominant type due to active renal reabsorption [11]. In contrast, urine almost exclusively contains the R-enantiomer of β-AIB, which is eliminated both by filtration and tubular secretion [9][10][11][12]. Persistently increased levels of β-AIB have been observed in individuals with a deficiency of R(−)-β-aminoisobutyratepyruvate aminotransferase.…”

Section: Introductionmentioning

confidence: 99%

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New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

Kuilenburg

Stroomer

Lenthe

et al. 2004

Biochemical Journal

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DPD (dihydropyrimidine dehydrogenase) constitutes the first step of the pyrimidine degradation pathway, in which the pyrimidine bases uracil and thymine are catabolized to beta-alanine and the R-enantiomer of beta-AIB (beta-aminoisobutyric acid) respectively. The S-enantiomer of beta-AIB is predominantly derived from the catabolism of valine. It has been suggested that an altered homoeostasis of beta-alanine underlies some of the clinical abnormalities encountered in patients with a DPD deficiency. In the present study, we demonstrated that only a slightly decreased concentration of beta-alanine was present in the urine and plasma, whereas normal levels of beta-alanine were present in the cerebrospinal fluid of patients with a DPD deficiency. Therefore the metabolism of beta-alanine-containing peptides, such as carnosine, may be an important factor involved in the homoeostasis of beta-alanine in patients with DPD deficiency. The mean concentration of beta-AIB was approx. 2-3-fold lower in cerebrospinal fluid and urine of patients with a DPD deficiency, when compared with controls. In contrast, strongly decreased levels (10-fold) of beta-AIB were present in the plasma of DPD patients. Our results demonstrate that, under pathological conditions, the catabolism of valine can result in the production of significant amounts of beta-AIB. Furthermore, the observation that the R-enantiomer of beta-AIB is abundantly present in the urine of DPD patients suggests that significant cross-over exists between the thymine and valine catabolic pathways.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

Kuilenburg

Stroomer

Lenthe

et al. 2004

Biochemical Journal

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“…Consistently, PMS analysis indicated that disturbances to the mitochondrial enzymes 2-oxoisovalerate dehydrogenase (acylating; 3-methyl-2-oxobutanoate), 3-hydroxyisobutyrate dehydrogenase, 3-hydroxyisobutyryl-CoA hydrolase, L-3-aminoisobutyrate transaminase, and methylmalonate-semialdehyde dehydrogenase, together with location-dependent 3-amino-isobutyrate transport and its exchange ( Figure 6 and Table S1), were further significant contributors towards the profound metabolic differences observed between GM1T2 and healthy human blood plasma samples. Notwithstanding, 3-AIB is also a terminal end-product of thymine catabolism, although as the (R) rather than the (S) stereoisomer configuration, as it is with BCAA catabolism [40]. However, both CS-and Ile-normalized plasma 3-AIB levels were found not to be significantly higher than those of the HC participants following Bonferroni-corrected univariate testing regimens.…”

Section: Bcaa Degradationmentioning

confidence: 81%

Rapid Identification of New Biomarkers for the Classification of GM1 Type 2 Gangliosidosis Using an Unbiased 1H NMR-Linked Metabolomics Strategy

Percival

Latour

Tifft

et al. 2021

Cells

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Biomarkers currently available for the diagnosis, prognosis, and therapeutic monitoring of GM1 gangliosidosis type 2 (GM1T2) disease are mainly limited to those discovered in targeted proteomic-based studies. In order to identify and establish new, predominantly low-molecular-mass biomarkers for this disorder, we employed an untargeted, multi-analyte approach involving high-resolution 1H NMR analysis coupled to a range of multivariate analysis and computational intelligence technique (CIT) strategies to explore biomolecular distinctions between blood plasma samples collected from GM1T2 and healthy control (HC) participants (n = 10 and 28, respectively). The relationship of these differences to metabolic mechanisms underlying the pathogenesis of GM1T2 disorder was also investigated. 1H NMR-linked metabolomics analyses revealed significant GM1T2-mediated dysregulations in ≥13 blood plasma metabolites (corrected p < 0.04), and these included significant upregulations in 7 amino acids, and downregulations in lipoprotein-associated triacylglycerols and alanine. Indeed, results acquired demonstrated a profound distinctiveness between the GM1T2 and HC profiles. Additionally, employment of a genome-scale network model of human metabolism provided evidence that perturbations to propanoate, ethanol, amino-sugar, aspartate, seleno-amino acid, glutathione and alanine metabolism, fatty acid biosynthesis, and most especially branched-chain amino acid degradation (p = 10−12−10−5) were the most important topologically-highlighted dysregulated pathways contributing towards GM1T2 disease pathology. Quantitative metabolite set enrichment analysis revealed that pathological locations associated with these dysfunctions were in the order fibroblasts > Golgi apparatus > mitochondria > spleen ≈ skeletal muscle ≈ muscle in general. In conclusion, results acquired demonstrated marked metabolic imbalances and alterations to energy demand, which are consistent with GM1T2 disease pathogenesis mechanisms.

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“…Even though we have no data for thymine, we tested a racemic mixture of 3aminoisobutyric acid (3-AIBA) as the sole source of nitrogen. Its D-stereoisomer is the final product of thymine degradation (119). To date, no aminotransferases have been identified in P. putida that show either D-or L-3-AIBA activity.…”

Section: Purines and Pyrimidinesmentioning

confidence: 99%

Nitrogen metabolism in Pseudomonas putida: functional analysis using random barcode transposon sequencing

Schmidt

Pearson

Incha

et al. 2021

Preprint

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Pseudomonas putida KT2440 has long been studied for its diverse and robust metabolisms, yet many genes and proteins imparting these growth capacities remain uncharacterized. Using pooled mutant fitness assays, we identified genes and proteins involved in the assimilation of 52 different nitrogen containing compounds. To assay amino acid biosynthesis, 19 amino acid drop-out conditions were also tested. From these 71 conditions, significant fitness phenotypes were elicited in 672 different genes including 100 transcriptional regulators and 112 transport-related proteins. We divide these conditions into 6 classes, and propose assimilatory pathways for the compounds based on this wealth of genetic data. To complement these data, we characterize the substrate range of three promiscuous aminotransferases relevant to metabolic engineering efforts in vitro. Furthermore, we examine the specificity of five transcriptional regulators, explaining some fitness data results and exploring their potential to be developed into useful synthetic biology tools. In addition, we use manifold learning to create an interactive visualization tool for interpreting our BarSeq data, which will improve the accessibility and utility of this work to other researchers.

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The absolute configuration of β-aminoisobutyric acid formed by degradation of thymine in man

Cited by 21 publications

References 11 publications

New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

Rapid Identification of New Biomarkers for the Classification of GM1 Type 2 Gangliosidosis Using an Unbiased 1H NMR-Linked Metabolomics Strategy

Nitrogen metabolism in Pseudomonas putida: functional analysis using random barcode transposon sequencing

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