X-Message-Number: 9552
Date: Mon, 27 Apr 1998 03:17:54 -0700 (PDT)
From: Doug Skrecky <>
Subject: cryoprotectants metabolized to formaldehyde

"Structural Determinants for Alcohol Substrates to be Oxidized to
Formaldehyde by Rat Liver Microsomes"
Archives of Biochemistry and Biophysics 298(1): 105-113 1992

Abstract:

    Glycerol can be oxidized to formaldehyde by rat liver microsomes and by
cytochrome P450. The ability of other alcohols to be oxidized to
formaldehyde was determined to evaluate the structural determinants of the
alcohol which eventually lead to this production of formaldehyde.
Monohydroxylated alcohols such as 1- or 2-propanol did not produce
formaldehyde when incubated with NADPH and microsomes. Geminal diols such
as 1,3-propanol, 1,3-butanediol, or 1,4-butanediol also did not yield
formaldehyde. However vicinal diols such as 1,2-propanediol or
1,2-butanediol produced formaldehyde. With 1,2-propanediol, the residual
two-carbon fragment was found to be acetaldehyde, while with
1,2-butanediol, the residual three-carbon fragment was propionaldehyde.
Oxidation of 1,2-propanediol to formaldehyde plus acetaldehyde involved
interaction with an oxident derived from H2O2 plus nonheme iron, since
production of the two aldehydic products was completely prevented by
catalase or glutathione plus glutathione peroxidase and by chelators such
as desferrioxamine or EDTA. The oxidant was not superoxide or hydroxyl
radical. Product formation was fivefold lower when NADH replaced NADPH, and
was inhibited by substrates, ligands, and inhibitors of cytochrome P450. A
charged glycol such as alpha-glycerophosphate (but not the geminal
beta-glycerophosphate) was readily oxidized to formaldehyde, suggesting
that interaction of the glycol with the oxident was occurring in solution
and not in a hydrophobic environment. These results indicate that the
carbon-carbon bond between 1,2-glycols can be cleaved by an oxident derived
from microsomal generated H2O2 and reduction of nonheme iron, with the
subsequent production of formaldehyde plus an aldehyde with one less carbon
than the initial glycol substrate.
end abstract:

Additional quote from text:

    "Preliminary experiments showed that the spin-trapping agent POBN
(alpha-[4-pyridyl-l-oxide]N-tert-butynitrone) inhibited formaldehyde
production from glycerol, suggesting that spin-trapping agent can interact
with the oxidant responsible for oxidizing glycols to formaldehyde."

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