14 December 2020

Levodopa from tomatoes

Tomato with beetroot gene – against Parkinson's disease

"First-hand science"

Using genetic engineering methods, it is possible to quickly create agricultural crops that will produce medicinal chemical compounds that are not characteristic of them. Such plants can be used directly for therapy, or as a source of the necessary substances. In this way, tomatoes have recently been created, in the fruits of which levodopa is synthesized – a drug used to combat Parkinson's disease.

L-DOPA.jpg

Figure from the press release of John Innes Centre Tomatoes offer affordable source of Parkinson's disease drug – VM.

There are many obstacles waiting for us on the way to a healthy old age, and one of them is Parkinson's disease. This slowly but steadily developing pathology of the central nervous system, accompanied by serious motor disorders (another name for this disease is "trembling paralysis"), threatens on average one out of every thousand people. Today, the disease is incurable, but there are means to slow down its course and improve the lives of patients.

One of these drugs is levodopa, a substance that is a precursor to the neurotransmitter dopamine. Dopamine, which ensures the functioning of the reward and reinforcement system, is better known as the "pleasure hormone". But it also regulates the work of the motor sphere: with a lack of dopamine, there is muscle stiffness, trembling, difficult movements, a characteristic stooping posture, shuffling gait.

Since the basis of Parkinson's disease is insufficient dopamine production in the brain as a result of the destruction and death of neurons involved in its synthesis, levodopa has been used since 1967 to compensate for the depletion of this neurotransmitter in such patients. Dopamine itself cannot be used for treatment directly, since it is "not allowed" into the brain by the blood-brain barrier that exists between the circulatory and central nervous systems. But its predecessor, levodopa, passes and serves as a raw material for the production of its own dopamine in the brain.

Usually levodopa is synthesized artificially, although it is quite expensive. In addition, sometimes patients suffer from the side effects of such a "chemical" drug. Meanwhile, there are also natural sources of levodopa, primarily the burning mucuna from the legume family, which is widely cultivated in the tropical zone as a forage and food plant. Mukuna seeds contain up to 10% levodopa! However, collecting them is difficult, since touching the plant causes irritation and allergic reactions, and the seeds themselves contain hallucinogens.

Levodopa is formed in nature from the amino acid tyrosine, and recently it turned out that this process is one of the intermediate stages of the synthesis of betalain pigments in ordinary red table beet (they, by the way, provide the red color of its root crops).

Scientists from the UK and Germany have introduced the beet gene encoding the enzyme responsible for the synthesis of levodopa from tyrosine into the genome of tomatoes, a widespread and well-genetically studied crop. As a result, the synthesis and accumulation of levopoda began in the fruits of the genetically engineered tomato, and the level of this substance turned out to be no lower than in other known plants-sources of the drug.

Article by Breitel et al. Metabolic engineering of tomato fruit enriched in L-DOPA is published in the journal Metabolic Engineering.

The daily dose, which is usually used for Parkinson's disease, is contained in about 2 kg of fresh modified fruits, but there are such tomatoes for the treatment of Parkinson's disease will not be required. The medicine will be extracted from them and, according to the researchers, it will be a cheap and simple method that does not require high technology. In addition, since levodopa itself has strong antioxidant properties, the fruits containing it are better stored and are more resistant to pathogenic fungi.

By the way, in low doses, extracts of burning mucuna are also used as an aphrodisiac and a remedy for male infertility. And for these purposes, the juice of transgenic tomatoes is quite suitable.

As for the use of "green genetic engineering" for medical purposes, such examples are multiplying every day. Thus, varieties of genetically modified rice have already been created, containing elevated levels of vitamin A and antioxidants, as well as substances that help lower blood pressure.

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