Vitamin C is possibly the most important small molecule whose biosynthetic pathway remained a mystery. That is until now.
A group of Dartmouth and UCLA researchers, who normally work on genes involved in aging and cancer in animals, discovered the last piece of the puzzle, they report in a study published online April 26 in the Journal of Biological Chemistry.
Dr. Steven Clarke of the UCLA Molecular Biology Institute and the Department of Chemistry and Biochemistry explains, "We were working on an interesting gene in worms." One insight led to another until, "We uncovered the last unknown enzyme in the synthesis of vitamin C in plants," said Dr. Charles Brenner of Dartmouth Medical School's Norris Cotton Cancer Center and Department of Genetics.
An essential vitamin for people, vitamin C is well known as an antioxidant and enzyme cofactor. Humans lost the ability to make vitamin C and need to take it up from dietary sources, particularly from plants.
Only in 1998 was a biosynthetic pathway proposed to explain how plants make vitamin C. Research since then has confirmed much of the pathway, although the gene responsible for the seventh step of the proposed 10-step pathway from glucose to vitamin C remained unknown.
The work began in an effort to understand the role of a gene in C. elegans, a tiny worm used as a model for aging studies by researcher Tara Gomez in Clarke's UCLA laboratory. The sequence of the gene suggested that it is related to a family of genes altered in cancer, termed HIT genes, that Brenner studies at Dartmouth.
Collaboration between the two laboratories revealed similarity of the worm gene to the product of the VTC2 gene of Arabidopis thaliana, a small roadside plant whose genetics have been well studied. Mutations in this plant gene had been previously linked to low levels of vitamin C. So the hunt was on to determine how its product would contribute to vitamin C synthesis.