Group of Purine Metabolism Disorders


Marie Zikánová



Veronika Barešová



Václava Škopová



Matyáš Krijt

Ph.D. student


Olga Součková

Ph.D. student



The group studies the pathology and physiology of purine metabolism, especially de novo purine synthesis (DNPS).

Currently, the group’s research focuses on the preparation and determination of DNPS metabolites and capturing new, as yet undescribed disorders in a population of patients with neurological impairments that have not yet been diagnosed. We prepared and characterized CRISPR-Cas9 genome-edited HeLa cells deficient for particular steps of DNPS to model the possible genetically determined defects of the DNPS enzymes.

We also specialize in the study of the purinosome, the multi-protein complex DNPS enzymes. Our goal is to prepare a model system for in vivo study of the dynamic formation of purinosome and the molecular changes in physiological and pathological conditions.

Previously, the group focused on the adenylosuccinate (ADSL) lyase deficiency, a rare inherited metabolic disease of DNPS and purine nucleotide cycle.
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Zikanova M., Krijt J., Skopova V., Krijt M., Baresova V., Kmoch S. 2015. Screening for adenylosuccinate lyase deficiency using tandem mass spectrometry analysis of succinylpurines in neonatal dried blood. Clin Biochem, 48: 2-7

Jurecka A., Zikanova M., Kmoch S., Tylki-Szymanska A. 2015. Adenylosuccinate lyase deficiency. J Inherit Metab Dis, 38: 231-42

Jurecka A, Zikanova M, Jurkiewicz E, Tylki-Szymanska A. 2014. Attenuated adenylosuccinate lyase deficiency: a report of one case and a review of the literature. Neuropediatrics 45:50-55.

Krijt J, Skopova V, Adamkova V, Cermakova R, Jurecka A, Kmoch S, Zikanova M. 2013. The need for vigilance: false-negative screening for adenylosuccinate lyase deficiency caused by deribosylation of urinary biomarkers. Clin Biochem 46:1899-1901.

Duval N, Luhrs K, Wilkinson TG, 2nd, Baresova V, Skopova V, Kmoch S, Vacano GN, Zikanova M, Patterson D. 2013. Genetic and metabolomic analysis of AdeD and AdeI mutants of de novo purine biosynthesis: cellular models of de novo purine biosynthesis deficiency disorders. Mol Genet Metab 108(3):178-89.

Baresova V, Skopova V, Sikora J, Patterson D, Sovova J, Zikanova M, Kmoch S. 2012. Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency. Hum Mol Genet 21(7):1534-43.

Vliet LK, Wilkinson TG, 2nd, Duval N, Vacano G, Graham C, Zikanova M, Skopova V, Baresova V, Hnizda A, Kmoch S and others. 2011. Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency. Mol Genet Metab 102(1):61-8.

Zikanova M, Skopova V, Hnizda A, Krijt J, Kmoch S. 2010. Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency. Hum Mutat 31(4):445-55.

Zidkova L, Krijt J, Sladkova J, Hlobilkova A, Magner M, Zikanova M, Kmoch S, Friedecky D, Zeman J, Elleder M and others. 2010. Oligodendroglia from ADSL-deficient patient produce SAICAribotide and SAMP. Mol Genet Metab 101(2-3):286-8.

Jurecka A, Tylki-Szymanska A, Zikanova M, Krijt J, Kmoch S. 2008a. D: -Ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: Absence of positive effect. J Inherit Metab Dis 31 Suppl 2:329-32.

Jurecka A, Zikanova M, Tylki-Szymanska A, Krijt J, Bogdanska A, Gradowska W, Mullerova K, Sykut-Cegielska J, Kmoch S, Pronicka E. 2008b. Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency. Mol Genet Metab 94(4):435-42.

Mouchegh K, Zikanova M, Hoffmann GF, Kretzschmar B, Kuhn T, Mildenberger E, Stoltenburg-Didinger G, Krijt J, Dvorakova L, Honzik T and others. 2007. Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families. J Pediatr 150(1):57-61 e2.

Zikanova M, Krijt J, Hartmannova H, Kmoch S. 2005. Preparation of 5-amino-4-imidazole-N-succinocarboxamide ribotide, 5-amino-4-imidazole-N-succinocarboxamide riboside and succinyladenosine, compounds usable in diagnosis and research of adenylosuccinate lyase deficiency. J Inherit Metab Dis 28(4):493-9.

Kmoch S, Hartmannova H, Stiburkova B, Krijt J, Zikanova M, Sebesta I. 2000. Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients. Hum Mol Genet 9(10):1501-13.