Tomatinase

Tomatine (sometimes called tomatin or lycopersicin) is a glycoalkaloid, found in the stems and leaves of tomato plants, and in the fruits at much lower concentrations. It has fungicidal, antimicrobial, and insecticidal properties. Chemically pure tomatine is a white crystalline solid at standard temperature and pressure. Tomatine, as well as the closely related aglycon (or aglycone) derivative tomatidine have been shown to have multiple health benefits. Tomatine (sometimes called tomatin or lycopersicin) is a glycoalkaloid, found in the stems and leaves of tomato plants, and in the fruits at much lower concentrations. It has fungicidal, antimicrobial, and insecticidal properties. Chemically pure tomatine is a white crystalline solid at standard temperature and pressure. Tomatine, as well as the closely related aglycon (or aglycone) derivative tomatidine have been shown to have multiple health benefits. Tomatine is sometimes confused with the glycoalkaloid solanine, which is found in potatoes. 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 as 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 pimpinelifolium and the cultured species Lycopersicon esculentum. Alpha-tomatine (α-tomatine) belongs to the compound group steroidal glycoalkaloids. These compounds consist of an aglycon, which is a cholesterol derivative, and a carbohydrate chain, which in the case of α-tomatine consists of two d-glucose units, a d-galactose unit, and a d-xylose unit. In α-tomatine, the tetrasaccharide called lycotetraose is attached to the O-3 of the steroidal aglycone. At first it was thought that the synthesis of steroidal alkaloids only involved multiple steps of hydroxylation, oxidation and amination of cholesterol with arginine 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. 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 for example the Colorado beetle and to snails. It is also a defense against fungi. 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 reversible 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. Also, the disrupted membrane has an influence on sodium transport, by altering the membrane potential and reducing active sodium transport. When tomatine is orally ingested, the brush border of the intestine is damaged by the membrane-disruptive properties of tomatine, so increased uptake of macromolecules occurs. This damage to the epithelial barriers is dose-dependent.