Über die Wirkung des Histozyms auf die Homologen der Hippursäure.

Smorodinzew, I. A.

doi:10.1515/bchm2.1923.124.3-6.123

Cited by 12 publications

(1 citation statement)

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“…ACY1 activity was discovered as early as 1881, when Schmiedeberg coined the name "Histozym" (tissue en-zyme) for an intracellular enzymatic activity catalyzing the hydrolysis of N-benzoylglycine (hippuric acid) (Schmiedeberg 1881). In 1922, Smorodinzew reported on ACY1-catalyzed hydrolysis of various acylated amino acids (Smorodinzew 1922). Preferred substrates of ACY1 are aliphatic amino acids with a short-chain acyl moiety, especially N-acetyl-methionine (Birnbaum et al 1952).…”

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confidence: 99%

Mutations in ACY1, the Gene Encoding Aminoacylase 1, Cause a Novel Inborn Error of Metabolism

Sass

Mohr

Olbrich

et al. 2006

The American Journal of Human Genetics

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N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were identified through organic acid analyses using gas chromatography-mass spectrometry, revealing increased urinary excretion of several N-acetylated amino acids, including the derivatives of methionine, glutamic acid, alanine, leucine, glycine, valine, and isoleucine. Nuclear magnetic resonance spectroscopy analysis of urine samples detected a distinct pattern of N-acetylated metabolites, consistent with ACY1 dysfunction. Functional analyses of patients' lymphoblasts demonstrated ACY1 deficiency. Mutation analysis uncovered recessive loss-of-function or missense ACY1 mutations in all four individuals affected. We conclude that ACY1 mutations in these children led to functional ACY1 deficiency and excretion of N-acetylated amino acids. Questions remain, however, as to the clinical significance of ACY1 deficiency. The ACY1-deficient individuals were ascertained through urine metabolic screening because of unspecific psychomotor delay (one subject), psychomotor delay with atrophy of the vermis and syringomyelia (one subject), marked muscular hypotonia (one subject), and follow-up for early treated biotinidase deficiency and normal clinical findings (one subject). Because ACY1 is evolutionarily conserved in fish, frog, mouse, and human and is expressed in the central nervous system (CNS) in human, a role in CNS function or development is conceivable but has yet to be demonstrated. Thus, at this point, we cannot state whether ACY1 deficiency has pathogenic significance with pleiotropic clinical expression or is simply a biochemical variant. Awareness of this new genetic entity may help both in delineating its clinical significance and in avoiding erroneous diagnoses.

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confidence: 99%