A strong developmental isotope effect in Caenorhabditis elegans induced by 5,5-deuterated lysine.
Amino Acids
; 49(5): 887-894, 2017 05.
Article
en En
| MEDLINE
| ID: mdl-28161800
ABSTRACT
Effects exerted by heavy isotope substitution in biopolymers on the functioning of whole organisms have not been investigated. We report on the decrease of permissive temperature of nematodes fed with bacteria containing 5,5-D2-lysine. We synthesized 5,5-dideuterolysine and, taking advantage of lysine being an essential amino acid, showed that C. elegans with modified lysine poorly develop from larvae into fertile adult hermaphrodites. This effect occurs only at high temperature within the permissible range for C. elegans (25 °C) and completely vanishes at 15 °C. The only known metabolic involvement of C5 in lysine is in post-translational modification through lysyl hydoxylases. Indeed, siRNA experiments showed that deficiency of let-268/plod lysyl-hydroxylase/glycosydase further amplifies the isotope effect making it apparent even at 20 °C, whereas control siRNAs as well as another lysyl-hydroxylase (psr-1/jmjdD) siRNA do not. We report for the first time that a site-specific deuteration may strongly affect the development of the whole animal organism especially under the conditions of deficiency of the corresponding enzyme. These findings provide the basis for our ongoing efforts to employ isotope effects for fine tuning of metabolic pathways to mitigate pathological processes.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Deuterio
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Escherichia coli
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Lisina
Límite:
Animals
Idioma:
En
Revista:
Amino Acids
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Rusia