Deuterium Oxide and Deuteration Effects on Biomolecules

Preparation of methanediamine (CH 2 (NH 2 ) 2 )—A precursor to nucleobases in the interstellar medium

“…This can only happen if the molecule being ionized contains six or more hydrogen atoms, which excludes the possibility that H 4 N 3 is being observed and confirms that the correct molecular formula is CH 6 N 2 . It was also noted that the peak of the temperature programmed desorption (TPD) profiles observed in this deuterated ice shifts from 152 K to 160 K. This is likely due to an increase of molecular weight by 6 amu resulting in an elevated sublimation temperature ( 35 ).…”

Reverse stable isotope labelling with Raman spectroscopy for microbial proteomics

“…Unlike carbon SIP, 100% DSIP is reported to be toxic as it affects the hydrogen bonding by increasing the distance resulting in affecting hydrogen bond molecular structure [31, 61, 62]. It is also reported that deuterium lowers the thermal denaturation of proteins and affects lipid bilayers and protein‐lipid interactions [63]. In Figure 3C, we can see that at 0 h, there is no peak in the Raman silent region indicating no deuterium incorporation in the cell.…”

Systemic deuteration of SCID mice using the water‐isotopologue deuterium oxide (D2O) inhibits tumor growth in an orthotopic bioluminescent model of human pancreatic ductal adenocarcinoma

“…18,19,21,22 As to the unknown origin of a D 2 O-induced proteotoxic stress response (observed by us for the first time in PDAC cells), it is tempting to speculate that alteration of protein confirmational stability might trigger ER stress, consistent with prior research that already has reported the paradoxical conformational rigidification and increased thermal stability of proteins due to the increased strength of deuterium-substituted hydrogen bonds and hydrophobic interactions. 8,12,13,[45][46][47][48] In this context, it is interesting that D 2 O exposure downregulated expression of HSPA1A and HSPA8 (encoding distinct Hsp70 family members) observable at both the mRNA and protein levels (Figures 2 and 3), and systemic deuteration caused an analogous modulation of tissue epitopes (upregulation of p-eIF2α and DDIT3/CHOP with downregulation of HSP70) detectable in orthotopic tumor tissue (Figure 6C). Likewise, the specific role of JNK signaling (shown before to occur as a consequence of ER stress downstream of IRE1-activation controlling proapoptotic processes) in the execution of the D 2 O-induced cellular stress response remains to be explored, and it is tempting to speculate that JNK might play a significant apoptogenic role since JNK inhibition using SP600125 rescued cells from D 2 O-induced cell death, an observation in contrast with p38 inhibition (using SB203580) that did not impact D 2 Oinduced loss of viability (data not shown).…”

“…Since its initial discovery as a natural heavy isotope variant (isotopologue) of dihydrogen oxide ( 1 H 2 O), extensive research has focused on the toxicological, biochemical, and pharmacological effects of 2 H 2 O (D 2 O, also referred to as 'heavy water'). [6][7][8] Deuterium stress is a specific isotopologue-induced form of cellular stress attributable mostly to isotope-( 2 H-vs. 1 H-) related changes in solvent effects and increased strength of deuterium-based hydrogen bonds after D/H exchange impacting (i) conformational stability of proteins and (ii) fidelity of nucleic acid base pairing (relevant to replication, transcription, and translation processes). [7][8][9][10][11][12][13] Strikingly, a significant body of evidence documents cancer cell-directed effects of D 2 O observable in vitro and in vivo based mostly on phenotypic observations; however, little information is available on D 2 Oresponsive molecular pathways and efficacy relevant to metastasis and tumor growth.…”

“…[6][7][8] Deuterium stress is a specific isotopologue-induced form of cellular stress attributable mostly to isotope-( 2 H-vs. 1 H-) related changes in solvent effects and increased strength of deuterium-based hydrogen bonds after D/H exchange impacting (i) conformational stability of proteins and (ii) fidelity of nucleic acid base pairing (relevant to replication, transcription, and translation processes). [7][8][9][10][11][12][13] Strikingly, a significant body of evidence documents cancer cell-directed effects of D 2 O observable in vitro and in vivo based mostly on phenotypic observations; however, little information is available on D 2 Oresponsive molecular pathways and efficacy relevant to metastasis and tumor growth. [13][14][15][16][17] The unfolded protein response (UPR), an intracellular stress response pathway elicited by proteotoxic insult that monitors, maintains, and restores homeostasis upon endoplasmic reticulum (ER) stress, is known to be dysregulated in cancer.…”