UCLA and Dartmouthscientists have identified a crucial enzymein plant vitamin C synthesis, which could lead to enhanced crops. The discovery now makes clear the entire 10-step process by which plantsconvert glucose into vitamin C, an important antioxidant in nature.

"If we can find ways to enhance the activity of this enzyme, it maybe possible to engineer plants to make more vitamin C and produce better crops," said Steven Clarke,UCLA professor of chemistry and biochemistry, director of UCLA's MolecularBiology Institute and co-author of the research study, to be published as a'Paper of the Week' in the Journal of Biological Chemistry and currentlyavailable online.

"We hit on gold," Clarkesaid, "because we now have a chance to improve human nutrition and to increasethe resistance of plants to oxidative stress. Plants may grow better with morevitamin C, especially with more ozone in the atmosphere due to pollution."

Carole Linster, a UCLA postdoctoral fellow inchemistry and biochemistry and lead author of the study, discovered thecontrolling enzyme, GDP-L-galactose phosphorylase,which serves as the biosynthetic pathway by which plants manufacture vitamin C.

"Ourfinding leads to attractive approaches for increasing the vitamin C content inplants," Linster said. "We now have twostrategies to provide enhanced protection against oxidative damage: Stimulatethe endogenous activity of the identified enzyme or engineer transgenic plantswhich overexpress the gene that encodes the enzyme."

Whenlife on Earth began, there was almost no oxygen, Clarke noted.

"Twobillion years ago, plants devised an efficient way to get sunlight to makesugar from carbon dioxide that produced oxygen as a waste product; that wasteproduct probably killed off most of all living species at that time," Clarkesaid. "The only organisms that survived developed defenses against it, and oneof the best defenses is vitamin C. Plants learned how to make vitamin C toprotect themselves."

Priorto the new research, vitamin C may have been the most important small moleculewhose biosynthetic pathway remained a mystery.

Anessential vitamin for humans, vitamin C is also an important antioxidant foranimals and plants. Humans do not have the ability to make vitamin C and get itfrom dietary sources, especially from plants. It was not until 1998 that abiosynthetic pathway was proposed to explain how plants make this compound.Research confirmed much of the pathway, although one crucial missing linkcontinued to baffle scientists and remained unknown until this new research.

Clarke,who studies the biochemistry of aging, said the finding is an example ofserendipity in science.

Theresearch started as an effort to understand the role of a gene in Caenorhabditis elegans, a tiny worm usedas a model for aging studies by Tara Gomez, a former UCLA undergraduate in Clarke's laboratory and now a graduatestudent at the California Institute of Technology. The gene's sequencesuggested that it was related to a family of genes altered in cancer, known asHIT genes; these genes are studied in the laboratory of Charles Brenner at the Norris CottonCancer Centerat Dartmouth Medical School.

Collaborationbetween Clarke's and Brenner's laboratories revealed a similarity between theworm gene and the product of the VTC2 gene of Arabidopsis thaliana, a small roadside plant. Mutations in thisgene had been previously linked to low levels of vitamin C. Linster and Gomezwere able to express and to purify the plant VTC2 enzyme from bacteria. Theresearch team, led by Linster, produced the GDP-L-galactose substrate andreconstituted in test tubes the mysterious seventh step in vitamin C synthesis.

Clarke and Brenner liken thefirst six steps in vitamin C synthesis to a roadmap in which there are multiplepossible routes from glucose to a variety of cellular compounds. Once theGDP-L-galactose compound takes the exit marked "VTC2," however, the atoms arereconfigured to make vitamin C. The remaining three steps, like a curvingdriveway, "require some turns but no real choices and no backing up," Brennersaid.

The researchers are stillstudying what VTC2-related genes do in animals and how these genes may relateto aging and cancer.

The research was federallyfunded by the National Institute on Aging, the National Institute of GeneralMedical Sciences, the National Science Foundation, and the National CancerInstitute, and by a fellowship Linster received from the government of Luxembourg.

The scientific team includedUCLA researcher Lital Adler; Princeton undergraduate and former UCLA researchassistant Brian D. Young; and Dartmouthresearcher Kathryn Christensen.

About UCLA

UCLA is California's largest university, with anenrollment of nearly 37,000 undergraduate and graduate students. The UCLACollege of Letters and Science and the university's 11 professional schoolsfeature renowned faculty and offer more than 300 degree programs and majors.UCLA is a national and international leader in the breadth and quality of itsacademic, research, health care, cultural, continuing education and athleticprograms. Four alumni and five faculty have been awarded the Nobel Prize.