Tiglicaciduria in propionicacidaemia

Nyhan, William L.; Ando, Toshiyuki; Rasmussen, Karsten; Wadlington, William B.; Kilroy, Anthony W.; Cottom, Dennis; Hull, D

doi:10.1042/bj1261035

Cited by 34 publications

(9 citation statements)

References 9 publications

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“…All three of these defects have been associated with increased excretion of products in the isoleucine degxadative pathway prior to propionyl-CoA. Tiglic acid was identified with propionyl-CoA carboxylase deficiency [7] and /3-ketothiolase deficiency [3]. Butanone or a-methylacetoacetate, or both together, have been found in association with propionyl-CoA carboxylase deficiency [6], methylmalonyl-CoA mutase deficiency [8], and /?-ketothiolase deficiency [3].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine

1973

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ExtractCultured fibroblasts were shown to oxidize glycine to CO 2 -Isoleucine (10 HIM) inhibited glycine oxidation to CO 2 by about 60% in a concentration range of from 0.025 to 10 mM glycine in fibroblasts grown from a patient with ^-ketothiolase deficienty. Glycine oxidation by control cell lines was not inhibited by isoleucine. These studies demonstrate an interrelation between isoleucine catabolism and glycine oxidation in fibroblasts cultured from a patient with the ketotic hyperglycinemia syndrome. SpeculationHyperglycinemia and hyperglycinuria seen in the "ketotic hyperglycinemia" syndrome would appear to be secondary to accumulation of products of isoleucine catabolism. Thus, the varying levels of glycine reported in the serum and urine of these patients probably reflect differences in protein and isoleucine intake than rather primary blocks in glycine metabolism.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine

1973

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“…Results represent the mean and SE of [8][9][10][11][12] separate measurements, done in two separate experiments using cells grown for the same length of time in culture. Cells from the same culture bottle were used for incubation with and without isoleucine. '…”

Section: Resultsmentioning

confidence: 99%

“…Results represent the different between absorption at zero time and at 3 hr. Numbers represent the mean and SE of [8][9][10][11][12] measurements. Substrate only values differed somewhat from experiment to experiment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Glycine-Serine Interconversion in Cultured Human Fibroblasts by Products of Isoleucine Catabolism

Hillman

Otto

1974

Pediatr Res

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“…We assume that formation of Af-tiglylglycine is a detoxifying mechanism to rid the organism of this highly toxic organic acid. It is interesting to note that iV-tiglylglycine is also present in abnormal amounts in /?-methylcrotonylglycinuria of the biotin-responsive type [4,5], and the nonconjugated tiglate derivative is also present in abnormal amounts in some patients with propionicacidemia [13]. The mechanism (or mechanisms) for accumulation of this potent metabolite in such diverse metabolic disorders encourages us to believe that several different metabolites may inhibit tiglic acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

An Inherited Disorder of Isoleucine Catabolism Causing Accumulation of α-Methylacetoacetate and α-Methyl-β-hydroxybutyrate, and Intermittent Metabolic Acidosis

et al. 1973

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ExtractAt least 15 apparently inherited disorders of branched chain amino acid catabolism are now known; the 12th in chronological order of discovery is described in this report. It is a partial defect of the pathway of isoleucine oxidation beyond the level of oxidative decarboxylation and prior to the oxidation of propionate. The impairment of isoleucine catabolism appears to be situated at the "thiolase" reaction which converts a-methylacetoacetyl coenzyme A (CoA) to propionyl-CoA and acetyl-CoA. Two pedigrees (B and M) were investigated in detail. A third (S pedigree) has been brought to our attention for analysis of metabolites in urine but we have not performed additional studies in the latter. Each propositus was ascertained because of intermittent, odorless metabolic acidosis usually precipitated by intercurrent infection. Lethargy and coma occurred frequently during the periods of acidosis. One M sib, also presumably affected, died abroad in such an episode. Symptoms can be ameliorated by a low protein diet and careful attention to the management of intercurrent illness.A large excess of a-methyl-|8-hydroxybutyrate and a seemingly smaller excess of a-methylacetoacetate is present at all times in the urine of the three propositions. The M and S propositi also excrete i\f-tiglylglycine. The amounts of these unusual metabolites increase severalfold during acidosis and after a dietary load of L-isoleucine (75 mg/kg, 3 times daily for 2 days). The urine also contains butanone, particularly during acidosis. The amount of propionate and of glycine and other amino acids in blood and urine is always normal in our patients. Oxidation of L-isoleucine-U-14 G to GO 2 by cultured skin fibroblasts is about 45% of normal in the B propositus. The precise nature and location of the enzyme defect awaits clarification.Studies of family members reveal that presumed obligate heterozygotes excrete a small excess of a-methyl-8-hydroxybutyrate at all times; the amount can be increased by L-isoleucine feeding. The condition is apparently inherited in autosomal recessive fashion. It is likely that more than one form of mutant allele is responsible for the condition, as it is found in the three different pedigrees described here. Speculation

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Tiglicaciduria in propionicacidaemia

Cited by 34 publications

References 9 publications

Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine

Inhibition of Glycine Oxidation in Cultured Fibroblasts by Isoleucine

Inhibition of Glycine-Serine Interconversion in Cultured Human Fibroblasts by Products of Isoleucine Catabolism

An Inherited Disorder of Isoleucine Catabolism Causing Accumulation of α-Methylacetoacetate and α-Methyl-β-hydroxybutyrate, and Intermittent Metabolic Acidosis

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