Universität zu Köln

Johannes, Lena, Fu, Chun-Yu and Schwarz, Guenter (2022). Molybdenum Cofactor Deficiency in Humans. Molecules, 27 (20). BASEL: MDPI. ISSN 1420-3049

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Abstract

Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic-ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1, MOCS2, MOCS3, and GPHN. Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Johannes, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Fu, Chun-Yu UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-658108
DOI:	10.3390/molecules27206896
Journal or Publication Title:	Molecules
Volume:	27
Number:	20
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1420-3049
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYCLIC PYRANOPTERIN MONOPHOSPHATE; MOLYBDOPTERIN SYNTHASE GENE; SULFITE OXIDASE DEFICIENCY; BICISTRONIC MOCS1 GENE; GLYCINE RECEPTOR; ESCHERICHIA-COLI; STRUCTURAL-CHARACTERIZATION; GENOMIC STRUCTURE; DIETARY THERAPY; HUMAN GEPHYRIN Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/65810