Antithiamines

Some kinds of fish and Crustacea contain thiaminases. These enzymes cleave thiamin and thus inactivate the vitamin. Some plant phenols, e.g., chlorogenic acid, may possess antithiaminic properties, too, though their mechanism of action is so far not well understood. 

Thiamine status is influenced by the diet and by a variety of other factors, including its bioavailability in food products, ethanol consumption, the presence of antithiamine factors in the diet as well as folate and protein status. Ingested thiamine is fairly well absorbed, rapidly converted to phosphorylated forms, stored poorly, and excreted in the urine in a variety of hydrolyzed and oxidized products (TanPhaichitr et al., 1999). 

Vitamin Bj Vitamin Bj was discovered in 1926 by Jansen and Do-NATH, who synthesized it in its crystalline form from rice bran. It was initially called aneurine due to its antipolyneuropathic effect. Because it contains sulphur, Windaus correctly renamed it thiamine in 1932, a term by which it is still known today. The stixicture of this vitamin was described by Williams and Grewe in 1936. It is made up of pyrimidine and thiazole. Thiamine occurs in nature as free thiamine and in the form of thiamine monophosphate, diphosphate and triphosphate. A maximum amount of 8 — 15 mg is absorbed daily in the proximal portion of the small intestine. In the case of oversupply, thiamine is neither stored nor intestinally absorbed. A regular intake, with a daily requirement of about 1 mg, is necessary. The major coenzyme is thiamine pyrophosphate (TPP). Thiamine deficiency may be caused by malnutrition, impaired absorption, alcoholism, antithiamines or a lack of magnesium. Magnesium is an important cofactor for the coenzyme thiamine pyrophosphate. 

Thiamin-related diseases are the result of either insulficient thiamin intake (thiamin deficiency), poisoning by antithiamins, or of mutations in thiamin transporters or thiamin diphosphate-dependent enzymes. 

It is possible to introduce some changes in the vitamin molecule and still retain vitamin activity. For instance, when the methyl group in position 2 on the pyrimidine ring is replaced by ethyl, the product stiU exhibits activity, albeit much reduced. The corresponding propyl derivative is inactive the butyl derivative has antithiamine properties, and so have 2-alkylthio derivatives. 

The antithiamines studied best are pyrithiamine (XXIV) and oxythiamine (XXV). Pyrithiamine is the most potent antagonist of the two. 

Somogyi, j. C., and R. Bonicke Connection between chemical structure and antithiamine activity of various phenol derivatives. Intern. Z. Vitaminforsch. 39, 65—73 (1969). 

Yang PF, Pratt DE 1984 Antithiamin activity of polyphenolic antioxidants. J Food Sci 49 489-492... 

Human requirements for thiamine depend upon the body weight or size, the total metabolism or calories utilized, the maximal weight of the species, the amount of fat in the diet, the amount of thiamine being synthesized by bacterial action, the presence of antithiamine, the presence in food of enzymes destroying the vitamin, and various stress conditions. 

ANTITHIAMIN FACTORS IN FOOD. Certain raw fish and seafood—particularly carp, herring, clams, and shrimp— contain the enzyme thiaminase, which inactivates the thiamin molecule by splitting it into two parts. This effect has been seen in mink and fox fed 10 to 25% levels of certain raw fish, giving rise to a thiamin deficiency disease known as Chastek paralysis. This action can be prevented by cooking the fish prior to feeding, thereby destroying the thiaminase. Of course, humans seldom eat sufficient thiaminase-contain-ing raw fish or seafood to produce a thiamin deficiency. 

Canada requires manufacturers to prove E. arvense products are free of thiaminase-like activity (though the compound responsible for antithiamine action has not been identified). The action is based on the concern that irreversible brain damage may occur in thiamine-deficient individuals. ... 

Fukuoka, M. Chemical and Toxicological Studies on Bracken Fern, Pteridium aqui-linum var. latiusculum. VI. Isolation of 5-0-Caffeoylshikimic Acid as an Antithiamine Factor. Chem. Pharm. Bull. (Japan) 30, 3219 (1982). 

---