Tomatine

Tomatoes were brought to Europe in the early 1500s. The English botanist John Gerard was one of the first cultivators of the tomato plant. In his publication Grete Herball, he considered tomatoes poisonous due to their levels of what would later be called tomatine, plus high acid content. Consequently, tomatoes were generally not eaten in Britain until the mid-18th century. In 1837, the first medicinal tomato pills were advertised in the United States because of their positive effects upon the biliary organs. The product "Phelp's Compound Tomato Pills" was extracted from the tomato plant, and contained tomatine. The pills were made by the medic Guy R. Phelps, who stated that the alkaloid tomatine was one of the most useful discoveries ever made. Tomatine then was said to be an antidote to mercury. In the mid 20th century, scientists from the US Department of Agriculture were the first to isolate tomatine from the wild tomato species Lycopersicon pimpinellifolium and the cultured species Lycopersicon esculentum. == Structure and biosynthesis ==

as the source of the incorporated nitrogen. Later the glycoalkaloid metabolism genes were discovered. These genes produce the glycoalkaloid metabolism enzymes, which are responsible for the synthesis of steroidal alkaloid aglycones in potato and tomato plants. The reaction these enzymes perform are shown in the figure 1. == Mechanism of action ==

Tomatine may play a major role in resistance of the tomato plant against fungal, microbial, insect, and herbivoral attack. The effects of the glycoalkaloids (to which tomatine belongs), can be divided in two main parts: the disruption of cellular membranes and the inhibition of the enzyme acetylcholinesterase. Tomatine is responsible in tomato plants for resistance against animals such as snails and the Colorado beetle. It is also a defense against fungi. Membrane disruption The membrane disruptive properties of tomatine are caused by the ability to form 1:1 complexes with cholesterol. A possible mechanism of the membrane disruption by glycoalkaloids is displayed in figure 2. First, the aglycon part of tomatine binds reversibly to sterols in the membrane (figure 2, part 2). When this reaches a certain density, the glycosidic residues of the glycoalkaloids interact with each other by electrostatic interactions. This interaction catalyzes the development of an irreversible matrix of glycoalkaloid-sterol complexes (figure 2, part 4). In this way, the sterols from the external membrane are immobilized and membrane budding will arise. Tubular structures are formed, because of the structure of tomatine (figure 2, part 6). This membrane disruption causes cell death by cell leakage. Tomatine is effective against fungi at pH 8 but not at pH 4. A possible explanation for this is that the tomatine only in the deprotonated form binds to cholesterol to form the earlier mentioned complexes. == Metabolism ==

Even now, little is known about the bioavailability, pharmacokinetics and metabolism of the glycoalkaloids in humans. The metabolite tomatidine can be hydrolyzed further by membrane-bound CYP-450 oxygenases. == Uses ==

Tomatine has been used as a reagent in analytical chemistry for precipitating cholesterol from solution. Also, tomatine is known to be an immune adjuvant in connection with certain protein antigens. == Toxicity ==

The possible risks of tomatine for humans have not been formally studied, so no NOAEL can be deduced. The toxicity of tomatine has only been studied on laboratory animals. The symptoms of acute tomatine poisoning in animals are similar to the symptoms of poisoning by solanine, a potato glycoalkaloid. These symptoms include vomiting, diarrhea, abdominal pain, drowsiness, confusion, weakness, and depression. Generally, tomatine is regarded to cause less toxic effects to mammals than other alkaloids such as solanine. The human consumption of moderate amounts of tomatine seems to occur without notable toxic effects. This is reinforced by the widespread consumption of "pickled green" and "fried green tomatoes" and the consumption of high-tomatine tomatoes (a variant of L. esculentum var. cerasiforme, better known as the "cherry tomato", indigenous to Peru) with very high tomatine content (in the range of 500–5000 μg/kg of dry weight). New York Times food science writer Harold McGee found scant evidence for tomato toxicity in the medical and veterinary literature, and observed that dried tomato leaves (which contain higher concentrations of alkaloids than the fruits) are occasionally used as a food flavoring or garnish, without problems. He also reported that an adult human would probably have to eat over half a kilogram of tomato leaves to ingest a toxic (not necessarily lethal) dose. == See also ==