Endogenous production of lipoic acid is essential for mouse development.
Authors Yi X, Maeda N
Submitted By Nobuyo Maeda on 2/23/2009
Status Published
Journal Molecular and cellular biology
Year 2005
Date Published 9/1/2005
Volume : Pages 25(18) : 8387 - 8392
PubMed Reference 16135825
Abstract alpha-Lipoic acid (LA) is a cofactor for mitochondrial alpha-ketoacid
dehydrogenase complexes and is one of the most potent, natural antioxidants.
Reduction of oxidative stress by LA supplementation has been demonstrated in
patients with diabetic neuropathy and in animal models. To determine how normal
development or pathological conditions are affected by genetic alterations in
the ability of mammalian cells to synthesize LA and whether dietary LA can
circumvent its endogenous absence, we have generated mice deficient in lipoic
acid synthase (Lias). Mice heterozygous for disruption of the Lias gene develop
normally, and their plasma levels of thiobarbituric acid-reactive substances do
not differ from those of wild-type mice. However, the heterozygotes have
significantly reduced erythrocyte glutathione levels, indicating that their
endogenous antioxidant capacity is lower than those of wild-type mice.
Homozygous embryos lacking Lias appear healthy at the blastocyst stage, but
their development is retarded globally by 7.5 days postcoitum (dpc), and all the
null embryos die before 9.5 dpc. Supplementing the diet of heterozygous mothers
with LA (1.65 g/kg of body weight) during pregnancy fails to prevent the
prenatal deaths of homozygous embryos. Thus, endogenous LA synthesis is
essential for developmental survival and cannot be replaced by LA in maternal
tissues and blood.

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina


Liaslipoic acid synthetase