X-Message-Number: 32605
Date: Thu, 3 Jun 2010 22:23:27 -0700 (PDT)
Subject: carbon monoxide likely reduces glycerol toxicity

Biochem Pharmacol. 1990 Feb 15;39(4):697-705.

Oxidation of glycerol to formaldehyde by rat liver microsomes. Effects of 
cytochrome P-450 inducing agents.

Winters DK, Cederbaum AI. Department of Biochemistry, Mount Sinai School of 
Medicine, New York, NY 10029.

    Glycerol was shown recently to be metabolized to formaldehyde by microsomes 
    from chowfed control rats (Winters et al., Biochem Biophys Res Commun 153: 
    612-617, 1988). In the present study, experiments were carried out to 
    evaluate the oxidation of glycerol by microsomes isolated from rats treated 
    with inducers of different isozymes of cytochrome P-450. The oxidation of 
    glycerol to formaldehyde was increased in microsomes from rats treated with 
    pyrazole, ethanol or acetone relative to their respective controls, but not 
    after treatment with phenobarbital or 3-methylcholanthrene. This reaction 
    was sensitive to inhibition by carbon monoxide and was inhibited by 
    compounds known to be effective substrates for P-450j, e.g. aniline, 
    ethanol, pyrazole and 4-methylpyrazole. Treatment with pyrazole caused an 
    increase in Vmax for glycerol oxidation but did not affect affect the Km 
    (about 15 mM) for glycerol, as compared to saline controls. Evidence that 
    the product of glycerol metabolism is formaldehyde was provided by the 
    observation that this product served as a substrate for the 
    glutathione-dependent formaldehyde dehydrogenase, and the amount of 
    formaldehyde detected was identical to that detected by the Nash reaction. 
    By utilizing [14C]glycerol, and coupling the formaldehyde dehydrogenase 
    reaction to the formate dehydrogenase reaction, 14CO2 could be detected, 
    indicating that the formaldehyde produced was derived from the added 
    glycerol. These results suggest that that glycerol is not metabolically 
    inert when added to microsomes but serves as an effective substrate for the 
    cytochrome P-450j isozyme, extending the alcohol substrate specificity of 
    this enzyme to poly-ols. The production of formaldehyde from glycerol may 
    require caution since glycerol is often present in microsomal or 
    reconstituted systems.
PMID: 2306278

Biochem Biophys Res Commun. 1988 Jun 16;153(2):612-7.
Oxidation of glycerol to formaldehyde by rat liver microsomes.

Winters DK, Clejan LA, Cederbaum AI. Department of Biochemistry, Mount Sinai 
School of Medicine, (CUNY), N.Y. 10029.

    Rat liver microsomes catalyzed the oxidation of glycerol to a Nash-reactive 
    material in a time- and protein-dependent manner. Omission of the glycerol 
    or the microsomes or any of the components of the NADPH-generating system 
    resulted in almost a complete loss of product formation. Apparent Km and 
    Vmax values for glycerol oxidation were about 18 mM and 2.5 nmol 
    formaldehyde per min per mg microsomal protein. Carbon monoxide inhibited 
    glycerol oxidation indicating a requirement for cytochrome P-450. That the 
    Nash-reactive material was formaldehyde was validated by a 
    glutathione-dependent formaldehyde dehydrogenase positive reaction. These 
    studies indicate that glycerol is not inert when utilized with microsomes or
    reconstituted mixed function oxidase systems, and that the production of 
    formaldehyde from glycerol may interfere with assays of other substrates 
    which generate formaldehyde as product.
PMID: 3382392

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