A liver urocanase deficiency

Kalafatić, Z; Lipovac, K; Jezerinac, Z; Juretić, Dubravka; Dumić, M; Zurga, B; Res, Ladislav

doi:10.1016/0026-0495(80)90209-7

Cited by 12 publications

(8 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9,10 Urocanase deficiency in the liver seems to be a cause of mental retardation. 11,12 Here, we are concerned with the urocanase from Pseudomonas putida. Under physiological conditions, it is a dimer with a molecular peptide mass of 2!60,781 Da.…”

Section: Introductionmentioning

confidence: 99%

Structure and Action of Urocanase

Kessler

Rétey

Schulz

2004

Journal of Molecular Biology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Structure and Action of Urocanase

Kessler

Rétey

Schulz

2004

Journal of Molecular Biology

View full text Add to dashboard Cite

“…These discoveries expand knowledge of other biosynthetic GLU pathway in neurons beyond the quintessential pathways, such as the tricarboxylic acid cycle originating with glucose and the GLU-glutamine cycle between neurons and astrocytes (Bé langer et al, 2011). The presence of HIS-UCA-GLU pathway in the CNS is supported by the clinical findings showing that histidinemia and urocanic aciduria, which are autosomal recessive metabolic disorders due to histidase and urocanase deficiency respectively, are both associated with multiple central developmental symptoms, including learning difficulties, speech or language disturbances, subnormal intelligence, and mental retardation (Davies and Robinson, 1963;Espinó s et al, 2009;Kalafatic et al, 1980;Lott et al, 1970;Raisová and Hyá nek, 1986), presumably because of lower GLU synthesis in neurons during brain development, based upon our findings. This study indicates that the single-cell MS technology is a valuable tool to study novel metabolic pathways in the brain at the single-cell level.…”

Section: Discussionmentioning

confidence: 97%

Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain

Zhu

Wang

Yao

et al. 2018

Cell

134

View full text Add to dashboard Cite

Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes.

show abstract

“…This finding would indicate that the urocanase deficiency is a hereditary disease. To date, four symptomatic children with urocanic aciduria have been reported: two isolated cases3 16 and two affected sisters 4. In the sisters’ family, previous generations were also possibly affected, which would suggest autosomal dominant inheritance.…”

Section: Discussionmentioning

confidence: 99%

“…The latter two neurological signs have not previously been associated with urocanase deficiency 1 3 4. Histidine catabolism comprises several metabolic steps leading to the synthesis of 5–10-methenyltetrahydrofolate (MTHF), a precursor of the purine ring and other folate metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…Urocanase deficiency was first reported in 1971,3 and mental retardation was described as the main neurological sign in a single case. Later on, two sisters were reported presenting mental retardation plus ataxia and dysarthria 4. In these cases, the defect could be found by indirect analysis of some metabolites of the histidine pathway in blood and urine and by the quantification of deficient urocanase activity in liver biopsies.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

Espinós

Pineda

Martínez‐Rubio

et al. 2009

Journal of Medical Genetics

View full text Add to dashboard Cite

Urocanase is an enzyme in the histidine pathway encoded by the UROC1 gene. This report describes the first putative mutations, p.L70P and p.R450C, in the coding region of the UROC1 gene in a girl with urocanic aciduria presenting with mental retardation and intermittent ataxia. Computed (in silico) predictions, protein expression studies and enzyme activity assays suggest that none of the mutations can produce a fully functional enzyme. The p.L70P substitution, which probably implies the disruption of an alpha-helix in the N-terminus, would alter its properties and therefore, its function. The p.R450C change would render impossible any interaction between urocanase and its substrate and would loss its enzyme activity. Consequently, these studies suggest that both mutations could alter the correct activity of urocanase, which would explain the clinical and biochemical findings described in this patient.

show abstract

A liver urocanase deficiency

Cited by 12 publications

References 15 publications

Structure and Action of Urocanase

Structure and Action of Urocanase

Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain

Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

Contact Info

Product

Resources

About