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Maybe one day you can eat grapefruit again

Maybe one day you can eat grapefruit again

You may be one of the millions of people who have seen a surprisingly specific warning like this on the labels of the medications you take:

Avoid eating grapefruit or drinking grapefruit juice while taking this medication.

Such warnings are issued for dozens of substances, including docetaxel, a cancer drug; erythromycin, an antibiotic; and some statins, the cholesterol-lowering drugs prescribed to more than a third of American adults over 40.

The problem is a series of molecules, furanocoumarins. High amounts of furanocoumarins impair human liver enzymes, among other things. In their presence, medications can build up in the body at unhealthy levels. And grapefruits and some related citrus fruits are full of them.

However, there is no such warning for other types of citrus, such as tangerines and other oranges. Citrus researchers at the Volcani Center in Israel reported Wednesday in the journal The New Phytologist that by crossing tangerines and grapefruit, they discovered genes that produce furanocoumarins in some citrus fruits. This finding opens the possibility of producing grapefruits that do not require a warning label.

Scientists figured out the structures of the compounds years ago and put together a basic flowchart for making them, said Yoram Eyal, a professor at the Volcani Center. But the exact identity of the enzymes that catalyze the process—the proteins that cut a branch here or add a piece there—remained mysterious. He and his colleagues knew that one way to identify them was to cross citrus fruits high in furanocoumarin with those without furanocoumarin. If the offspring of such a cross had different amounts of these substances, it should be possible to determine the genes for the proteins by studying their genetics.

“We were afraid to approach this because it is very time-consuming and takes many years,” he said, noting how laborious it can be to grow new trees from seeds and assess their genetics. “But eventually we decided we needed to dive in.”

When they examined the offspring of a tangerine and a grapefruit, researchers saw something remarkable. Fifty percent of the young plants had a high proportion of furanocurmaines and 50 percent had none. This particular signature meant something very specific in terms of how the ability to produce these substances is inherited.

“We saw that there was only one gene that could have controlled it,” said Livnat Goldenberg, a researcher at the Volcani Center and lead author of the new study.

Researchers soon identified the gene that controls the production of furanocoumarins in leaves and fruits and produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD. It turns out that tangerines have a mutated form of this gene, which prevents the enzyme from working properly. This version appeared in all tangerine and orange varieties studied by the researchers and explains why they do not cause the same problems as grapefruit in people taking prescription medications. In these plants the production of furanocoumarin is interrupted.

With gene editing technology, it should be possible to change the gene in grapefruit as well, suggests Dr. Eyal in front. The Volcani Center team is currently studying this project.

Looking at how widespread this mutated version is in tangerines and some other citrus fruits, scientists speculate that a gene near the genome must play an important role in a highly valued trait. A citrus breeder who long ago chose an unknown quality must have inadvertently passed this furocoumarin-destroying version of the gene to an ancestor of modern mandarin and orange varieties.

All these years later, this person's work is coming to light under the eyes of geneticists who may one day put grapefruit back on the menu.

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