A strong developmental isotope effect in Caenorhabditis elegans induced by 5,5-deuterated lysine.

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.

journal_name

Amino Acids

journal_title

Amino acids

authors

Korneenko TV,Pestov NB,Hurski AL,Fedarkevich AM,Shmanai VV,Brenna JT,Shchepinov MS

doi

10.1007/s00726-017-2386-5

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

887-894

issue

5

eissn

0939-4451

issn

1438-2199

pii

10.1007/s00726-017-2386-5

journal_volume

49

pub_type

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