Autism Studies and Related Medical Conditions, January 2009 - TACA

Center for Hemostasis and Thrombosis Research, Tufts University School of
Medicine, Boston, MA 02111, USA.
The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the
posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in
precursor proteins containing the gamma-carboxylation recognition site (gamma-
CRS). During this reaction, glutamic acid is converted to gamma-carboxyglutamic
acid while vitamin KH2 is converted to vitamin K 2,3-epoxide. Recombinant
bovine carboxylase was purified free of gamma-CRS-containing propeptide and
endogenous substrate in a single-step immunoaffinity procedure. We show that
in the absence of gamma-CRS-containing propeptide and/or glutamatecontaining
substrate, carboxylase has little or no epoxidase activity. Epoxidase
activity is induced by Phe-Leu-Glu-Glu-Leu (FLEEL) (9.2 pmol per min per pmol
of enzyme), propeptide, residues -18 to -1 of proFactor IX (3.4 pmol per min per
pmol of enzyme), FLEEL and propeptide (100 pmol per min per pmol of enzyme),
and proPT28 (HVFLAPQQARSLLQRVRRANTFLEEVRK, residues -18 to +10 of
human acarboxy-proprothrombin), (5.3 pmol per min per pmol of enzyme).
These results indicate that in the absence of propeptide or glutamate-containing
substrate, oxygenation of vitamin K by the carboxylase does not occur. Upon
addition of propeptide or glutamate-containing substrate, the enzyme is
converted to an active epoxidase. This regulatory mechanism prevents the
generation of a highly reactive vitamin K intermediate in the absence of a
substrate for carboxylation.
PMID: 9256436 [PubMed - indexed for MEDLINE
Tchantchou F, Graves M, Shea TB. Expression and activity of methionine cycle genes
are altered following folate and vitamin E deficiency under oxidative challenge:
modulation by apolipoprotein E-deficiency. Nutr Neurosci. 2006 Feb-Apr;9(1-2):17-24.
Department of Biological Sciences, Center for Cellular Neurobiology and
Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA
01854, USA.
Folate deficiency increases neuronal oxidative damage and potentiates the
deleterious effects of apolipoprotein E (ApoE) deficiency. Mice lacking ApoE
(ApoE -/- mice) upregulate the expression and activity of another enzyme,
glutathione synthase (GS), when deprived of folate, in an apparent attempt to
compensate for increased oxidative damage. Herein, we examined the influence
of ApoE and folate deficiency on expression and activity of several enzymes of
the methionine cycle. Expression and activity of methylene tetrahydrofolate
reductase was increased in the order ApoE +/+ < ApoE +/- < ApoE -/- in
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