HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

The Missing Link in Vitamin C Biosynthesis

Vitamin C is an important antioxidant and enzyme cofactor in both animals and plants. Humans, unable to synthesize the vitamin themselves, compensate by dietary intake, primarily from plants. Plants synthesize the vitamin via the Smirnoff-Wheeler pathway which converts D-glucose to L-ascorbate in a 10-step process. The only step in the pathway that has not been linked to a gene product is the conversion of GDP-L-galactose to L-galactose 1-phosphate.

The Smirnoff-Wheeler pathway for vitamin C biosynthesis.

In this Paper of the Week, Carole L. Linster and colleagues show that the product of the Arabidopsis thaliana VTC2 gene is the missing enzyme that catalyzes this step. Previous work had shown that vtc2 mutants do not make vitamin C. In this manuscript, the authors cloned the VTC2 gene from A. thaliana and expressed the recombinant protein. They found that VTC2 is a member of the GalT/Apa1 branch of the histidine triad protein superfamily and showed that it catalyzes the conversion of GDP-L-galactose to L-galactose 1-phosphate in a reaction that consumes inorganic phosphate and produces GDP. The significance of this work rests on the fact that the enzymes catalyzing each of the 10 steps of the Smirnoff-Wheeler pathway from glucose to ascorbate have now been identified.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 18879-18885

How Antibodies May Fight Alzheimer Disease

Immunotherapy against -amyloid peptide (A) is a leading therapeutic direction for Alzheimer disease. Experimental studies in transgenic mouse models of the disease have demonstrated that A immunization reduces A plaque pathology and improves cognitive function. However, the biological mechanisms by which A antibodies reduce amyloid accumulation in the brain remain unclear.

Treatment with A antibody 6E10 reduces A42 immunofluorescence.

In this Paper of the Week, Davide Tampellini and colleagues show that A antibodies decrease levels of intracellular A in Alzheimer disease mouse mutant neurons in culture. This reduction in cellular A appears to require that the antibody bind to the extracellular A domain of the amyloid precursor protein (APP) and be internalized. The authors also found that treatment with A antibodies protects against synaptic alterations that occur in APP mutant neurons.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 18895-18906

[More Papers of the Week]