Excessive excretion of β‐alanine and of 3‐hydroxypropionic,R‐ andS‐3‐aminoisobutyric,R‐ andS‐3‐hydroxyisobutyric andS‐2‐(hydroxymethyl)butyric acids probably due to a defect in the metabolism of the corresponding malonic semialdehydes

Abstract

A new metabolic disorder characterised by the excessive excretion of beta-alanine, 3-hydroxypropionic acid, R- and S-3-amino- and 3-hydroxyisobutyric acids and S-2-(hydroxymethyl)butyric acid is probably due to deficient activities of malonic, methylmalonic and ethylmalonic semialdehyde dehydrogenases. These dehydrogenation reactions could be mediated by one enzyme, or by enzymes with a common subunit, and both R- and S-methylmalonic semialdehydes seem to be equally affected. The patient is now aged 4 years and has developed normally. He has a persistent gross hypermethioninaemia which is probably unrelated to the other biochemical abnormalities.

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

“…The circled letters indicate confirmed (solid arrows) and putative (interrupted arrows) enzyme deficiencies: A ϭ dihydropyrimidine dehydrogenase deficiency; B ϭ dihydropyrimidinase deficiency; C ϭ ␤-alanine synthase deficiency; D ϭ hyper-␤-Aiburia; E ϭ a shared disorder of ␤-alanine and ␤-Aib catabolism. 27,28 that the meteorite contains all possible acyclic ␣-, ␤-, ␥-, and ␦-amino acids is consistent with a process of their formation involving a random combination of single C-precursors (e.g., radical species). ␤-Prolinebetaine 44,45 and trans-4-hydroxy-␤-prolinebetaine 46 could be considered cyclic ␤ 2 -amino acids and have been found in many species of marine algae.…”

“…29 3-Hydroxyisobutyric acid was about 75% (S)-and 25% (R)-configuration, and all of the 2-ethyl-3-hydroxypropionic acid (i.e., a metabolite of the minor pathway of the isoleucine catabolism) was the (S)-isomer. 27 A defective methylmalonate semialdehyde dehydrogenase was proposed by studying the metabolism of valine in intact fibroblasts from a patient. The oxidation of [1Ϫ 14 C]valine to 14 CO 2 was normal, but the oxidation of [2Ϫ 14 C]valine to 14 CO 2 was undetectable, indicating a severe block in valine metabolism below the level of isobutyryl-CoA.…”

Chiral compounds in metabolism: a look in the molecular mirror

“…A single report on the ®nding of increased R and S forms of aminoisobutyric, hydroxyisobutyric and hydroxymethylbutyric acids in a Pakistani patient suggested defects at the level of semialdehyde dehydrogenase [38]. No further cases have been described.…”

Inborn errors of pyrimidine degradation: Clinical, biochemical and molecular aspects

“…Hyper-β-alaninuria with hyper-β-amino isobutyric aciduria can also be caused by γ-vinyl-GABA, a drug that inhibits the relevant transaminase. Excessive urinary excretion of β-alanine and (RS)-β-aminoisobutyric acid in combination with β-hydroxypropionate, 3-hydroxyisobutyrate and (S)-2-(hydroxymethyl)butyrate has also been reported in a patient with reduced malonic semialdehyde dehydrogenase activity and deficient methylmalonic semialdehyde dehydrogenase (Pollitt et al 1985;Gray et al 1987). Bacterial metabolism can be the cause of N-carbamyl-β-amino aciduria instead of dihydropyrimidinuria in patients with DHP deficiency, thereby simulating UP deficiency (Van Gennip et al 1993).…”