X-Message-Number: 31722
Date: Fri, 5 Jun 2009 09:52:32 -0700 (PDT)
From: 
Subject: threitol looks to be an interesting cryoprotectant


[Threitol is not however, a well researched cryoprotectant. A combination search
on PUBMED of keywords "freeze" and "threitol" yielded only three cites, below.]

J Biol Chem. 2009 Apr 29. [Epub ahead of print]

Cryoprotectant biosynthesis and the selective accumulation of threitol in the 
freeze tolerant alaskan beetle, Upis ceramboides.

  Walters KR Jr, Pan Q, Serianni AS, Duman JG. University of Notre Dame, United 
  States;

  Adult Upis ceramboides do not survive freezing in the summer, but tolerate 
  freezing to -60 degrees C in midwinter. The accumulation of two cryoprotective
  polyols, sorbitol and threitol, is integral to the extraordinary 
  cold-hardiness of this beetle. U. ceramboides is the only animal known to 
  accumulate high concentrations of threitol; however, the biosynthetic pathway 
  has not been studied. A series of (13)C-labeled compounds was employed to 
  investigate this biosynthetic pathway using (13)C{(1)H} NMR spectroscopy. In 
  vivo metabolism of (13)C-labeled glucose isotopomers demonstrates that C3-C6 
  of glucose become C1-C4 of threitol. This labeling pattern is expected for 
  four-carbon saccharides arising from the pentose phosphate pathway (PPP). In 
  vitro experiments show that threitol is synthesized from erythrose 4-phosphate
  (E4P), a C4 intermediate in the PPP. E4P is epimerized and/or isomerized to 
  threose 4-phosphate (T4P), which is subsequently reduced by a NADPH-dependent 
  polyol dehydrogenase and dephosphorylated by a sugar phosphatase to form 
  threitol. Threitol 4-phosphate appears to be the preferred substrate of the 
  sugar phosphatase(s), promoting threitol synthesis over that of erythritol. In
  contrast, the NADPH-dependent polyol dehydrogenase exhibits broad substrate 
  specificity. Efficient erythritol catabolism under conditions that promote 
  threitol synthesis, coupled with preferential threitol biosynthesis, appear 
  responsible for the accumulation of high concentrations of threitol (250 mM) 
  without concomitant accumulation of erythritol.
PMID: 19403530

[Only one company has done a serious investigation of threitol.]

Cryobiology. 1999 Nov;39(3):215-27.

Effects of solute methoxylation on glass-forming ability and stability of 
vitrification solutions

  Wowk B, Darwin M, Harris SB, Russell SR, Rasch CM. 21st Century Medicine, 
  Inc., 10844 Edison Court, Rancho Cucamonga, California, 91730, USA.

  The effects of replacing hydroxyl groups with methoxyl (OCH(3)) groups in the 
  polyols ethylene glycol (EG), propylene glycol (PG), glycerol, and threitol 
  were studied by differential scanning calorimetry (DSC) during cooling of 
  aqueous solutions to -150 degrees C and subsequent rewarming. For 35% (w/w) 
  PG, 40% EG, and 45% glycerol, a single substitution of a terminal hydroxyl 
  group with a methoxyl group reduced the critical cooling rate necessary to 
  avoid ice on cooling (vitrify) from approximately 500 to 50 degrees C/min. 
  This reduction was approximately equivalent to increasing the parent polyol 
  concentration by 5% (w/w). The critical warming rate calculated to avoid 
  formation of ice on rewarming (devitrification) was also reduced by methoxyl 
  substitution, typically by a factor of 10(4) for dilute solutions. Double 
  methoxylation (replacement of both terminal hydroxyls) tended to result in 
  hydrate formation, making these compounds less interesting. An exception was 
  threitol, for which substituting both terminal hydroxyls by methoxyls reduced 
  the critical rewarming rate of a 50% solution by a factor of 10(7) without any
  hydrate formation. These glass-forming and stability properties of 
  methoxylated compounds, combined with their low viscosity, enhanced 
  permeability, and high glass transition temperatures, make them interesting 
  candidate cryoprotective agents for cryopreservation by vitrification or 
  freezing. Copyright 1999 Academic Press.
PMID: 10600255

Nature. 1975 Dec 11;258(5535):519-20.

Production of threitol and sorbitol by an adult insect: association with 
freezing tolerance.
Miller LK, Smith JS.
PMID: 1196382

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