scholarly journals A gatekeeper helix determines the substrate specificity of Sjögren–Larsson Syndrome enzyme fatty aldehyde dehydrogenase

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Markus A. Keller ◽  
Ulrich Zander ◽  
Julian E. Fuchs ◽  
Christoph Kreutz ◽  
Katrin Watschinger ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Aldehyde Dehydrogenase ◽  
Fatty Aldehyde ◽  
Larsson Syndrome

Juvenile macular dystrophy associated with deficient activity of fatty aldehyde dehydrogenase in Sjögren-Larsson syndrome

2000 ◽  
Vol 130 (6) ◽  
pp. 782-789 ◽  
Author(s):  
Michèl A.A.P Willemsen ◽  
Johannes R.M Cruysberg ◽  
Jan J Rotteveel ◽  
Albert L Aandekerk ◽  
Peter H.M.F Van Domburg ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Macular Dystrophy ◽  
Fatty Aldehyde ◽  
Larsson Syndrome ◽  
Deficient Activity

A novel homozygous missense mutation in the fatty aldehyde dehydrogenase gene causes Sjögren-Larsson syndrome

2008 ◽  
Vol 52 (2) ◽  
pp. 136-138 ◽  
Author(s):  
Hajime Nakano ◽  
Eijiro Akasaka ◽  
Daiki Rokunohe ◽  
Shohei Yokoyama ◽  
Yuka Toyomaki ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Aldehyde Dehydrogenase ◽  
Fatty Aldehyde ◽  
Homozygous Missense Mutation ◽  
Dehydrogenase Gene ◽  
Larsson Syndrome

scholarly journals Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans

2020 ◽  
Author(s):  
Lidan Zeng ◽  
Xuesong Li ◽  
Christopher B. Preusch ◽  
Gary J. He ◽  
Ningyi Xu ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Therapeutic Strategy ◽  
Fatty Aldehyde ◽  
Peroxisome Proliferation ◽  
Neurologic Disorder ◽  
C Elegans ◽  
Catabolic Enzymes ◽  
Cellular Components ◽  
Fatty Aldehydes ◽  
Larsson Syndrome

AbstractThe intracellular level of fatty aldehydes is tightly regulated to minimize the formation of toxic aldehyde adducts of cellular components. Accordingly, deficiency of a fatty aldehyde dehydrogenase FALDH causes the neurologic disorder Sjögren-Larsson syndrome (SLS) in humans. However, cellular responses to unresolved, elevated fatty aldehyde levels are poorly understood. Based on lipidomic and imaging analysis, we report that the loss of endoplasmic reticulum-, mitochondria- and peroxisomes-associated ALH-4, the C. elegans FALDH ortholog, increases fatty aldehyde levels and reduces fat storage. ALH-4 deficiency in the intestine, cell-nonautonomously induces NHR-49/NHR-79-dependent hypodermal peroxisome proliferation. This is accompanied by the upregulation of catalases and fatty acid catabolic enzymes, as indicated by RNA sequencing. Such a response is required to counteract ALH-4 deficiency since alh-4; nhr-49 double mutant animals are not viable. Our work reveals unexpected inter-tissue communication of fatty aldehyde levels, and suggests pharmacological modulation of peroxisome proliferation as a therapeutic strategy for SLS.

Fatty aldehyde dehydrogenase, the enzyme downstream of tetrahydrobiopterin-dependent alkylglycerol monooxygenase

Pteridines ◽  
2013 ◽  
Vol 24 (1) ◽  
pp. 105-109 ◽  
Author(s):  
Markus A. Keller ◽  
Katrin Watschinger ◽  
Georg Golderer ◽  
Gabriele Werner-Felmayer ◽  
Ernst R. Werner
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Treatment Options ◽  
Ether Lipid ◽  
Signalling Pathways ◽  
Fatty Aldehyde ◽  
Ether Lipids ◽  
Lipid Degradation ◽  
Physiological Importance ◽  
Fatty Aldehydes ◽  
Larsson Syndrome

AbstractThe tetrahydrobiopterin-dependent degradation of ether lipids by alkylglycerol monooxygenase (AGMO) produces fatty aldehydes, which are toxic to cells. Therefore, it is of great physiological importance that these harmful compounds are converted into their corresponding, less toxic fatty acids by fatty aldehyde dehydrogenase (FALDH). Dysfunction of this enzyme causes Sjögren-Larsson syndrome. This severe inherited disorder is accompanied by symptoms such as ichthyosis, mental retardation and spasticity. Surprisingly, fatty alcohols and not fatty aldehydes were found to accumulate in fibroblasts of Sjögren-Larsson syndrome patients, suggesting that there can be wide-ranging alterations in the lipid composition of patient cells. In particular, this has to be considered when searching for possible treatment options for patients suffering from Sjögren-Larsson syndrome. For example, inhibition of fatty aldehyde producing ether lipid degradation would have multiple implications on ether lipid- and fatty alcohol-mediated signalling pathways.

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