Increased guanidino species in murine and human succinate semialdehyde dehydrogenase (SSADH) deficiency

Biochimica Et Biophysica Acta
Erwin E W JansenK M Gibson

Abstract

Mice with targeted deletion of the GABA-degradative enzyme succinate semialdehyde dehydrogenase (SSADH; Aldh5a1; OMIM 271,980) manifest globally elevated GABA and regionally decreased arginine in brain extracts. We examined the hypothesis that arginine-glycine amidinotransferase catalyzed the formation of guanidinobutyrate (GB) from increased GABA by quantifying guanidinoacetate (GA), guanidinopropionate (GP) and GB in brain extracts employing stable isotope dilution gas chromatographic-mass spectrometry. GA and GB were up to 4- and 22-fold elevated, respectively, in total and regional (cerebellum, hippocampus, cortex) brain extracts derived from SSADH(-/-) mice. Corresponding analyses of urine and cerebrospinal fluid derived from SSADH-deficient patients revealed significant (P<0.05) elevations of GA and GB in urine, as well as GB levels in CSF. These data suggest that GB may be an additional marker of SSADH deficiency, implicate additional pathways of pathophysiology, and identify the second instance of elevated GB in a human inborn error of metabolism.

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Citations

Sep 22, 2007·Journal of Inherited Metabolic Disease·A LatiniM Wajner
Dec 14, 2012·Orphanet Journal of Rare Diseases·David CheillanJoseph Vamecq
Nov 9, 2010·Molecular Genetics and Metabolism·Joseph VamecqGilbert Briand
Nov 7, 2015·Biochimie·Marie Joncquel-Chevalier CurtJoseph Vamecq
Jan 2, 2007·Neurochemistry International·Angela M SgaravattiCarlos Severo Dutra-Filho

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