Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Vitamins
Water-Soluble Vitamins
Vitamin B1

It is generally accepted that the hallmark of Water-Soluble Vitamins is the involvement of most of them in The formation of coenzyme molecules (see Table 7.1). These are low-molecular-weight non-protein Organic compounds, also known as prosthetic groups, which—together with the protein component (apoenzyme)—take a direct part in catalytic reactions. The coenzyme function has been conclusively proven for the following vitamins and Vitamin-like substances: B₁, B₂, B₆, B₁₂, PP, biotin, folic, para-aminobenzoic, pantothenic, and lipoic acids, as well as the fat-soluble coenzyme Q and pyrroloquinoline quinone (PQQ). Almost none of these are synthesized in the Human and Animal body; therefore, an insufficient intake or complete absence of these vitamins in the diet leads to significant Metabolic Disorders and The Development of the corresponding clinical syndrome characteristic of a given hypo- or avitaminosis.

Vitamin B₁ (thiamine; antineuritic), as noted earlier, was the first crystalline vitamin, isolated by C. Funk in 1912. Its chemical synthesis was achieved later. Alongside an amino group, vitamin B₁ contains sulfur atoms, which is why it was named thiamine. Its chemical Structure features two rings—pyrimidine and thiazole—connected by a methylene bridge. Both ring systems are synthesized separately as phosphorylated forms and then joined via a quaternary nitrogen atom.

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Thiamine is readily soluble in water. In acidic environments, aqueous thiamine solutions withstand heating to high temperatures without losing biological activity. Conversely, in neutral and especially alkaline environments, vitamin B₁ is rapidly destroyed upon heating. This explains the partial or even complete destruction of thiamine during food preparation, such as baking dough with The addition of sodium bicarbonate or ammonium carbonate. Upon oxidation, thiamine forms thiochrome, which exhibits blue fluorescence under UV irradiation. This property forms the basis for the Quantitative determination of thiamine.

Vitamin B₁ is easily absorbed in the intestine, but it does not accumulate in Tissues and exhibits no toxic properties. Excess dietary thiamine is rapidly excreted in the urine. The conversion of vitamin B₁ into its active form—thiamine pyrophosphate (TPP), also known as Thiamine diphosphate (TDP)—involves a specific ATP-dependent enzyme, thiamine pyrophosphokinase, found primarily in The Liver and Brain tissue. Experiments with ³²P-labeled ATP have proven the direct transfer of the pyrophosphate group to thiamine in the presence of this enzyme. TPP has the following structure:

If vitamin B₁ is ingested as TPP, the pyrophosphate group is cleaved from it by the action of intestinal pyrophosphatases.

A deficiency or lack of thiamine leads to a severe disease known as beriberi, which is widespread in several Asian and Indochinese countries where rice is the dietary staple. It should be noted that vitamin B₁ deficiency also occurs in European countries, where it is known as Wernicke's encephalopathy or Wernicke-Korsakoff syndrome, predominantly affecting The Cardiovascular system. Specific symptoms are associated with primary disorders in the functioning of both the cardiovascular and nervous systems, as well as the digestive tract. Currently, the view that human beriberi results exclusively from vitamin B₁ deficiency is being reconsidered. It is more likely that this condition represents a combined avitaminosis or polyavitaminosis, in which the body also suffers from a shortage of riboflavin, pyridoxine, vitamins PP, C, and others. Experimental B₁ avitaminosis has been induced in animals and human volunteers. Depending on the predominance of particular symptoms, several clinical types of deficiency are distinguished, notably the polyneuritic (dry) form of beriberi, in which Peripheral Nervous system disorders come to the forefront. The so-called wet (edematous) form of beriberi predominantly affects the cardiovascular system, although signs of polyneuritis are also observed. Finally, there is an acute cardiac form of the disease, termed pernicious, which leads to death As a result of acute Heart Failure. With the Introduction of crystalline thiamine preparations into medical practice, mortality has sharply declined, and rational approaches to the Treatment and Prevention of this disease have emerged.

The earliest symptoms of vitamin B₁ deficiency include impaired motor and secretory Functions of the digestive tract: loss of appetite, slowed intestinal peristalsis (atony), as well as psychiatric changes such as short-term memory loss and a tendency toward hallucinations. Cardiovascular manifestations include shortness of breath, palpitations, and precordial chest pain. As the avitaminosis progresses, symptoms of peripheral nervous system damage appear (degenerative changes in nerve endings and pathways), manifested by sensory disorders, tingling sensations, numbness, and pain along the nerve trunks. These lesions culminate in contractures, atrophy, and paralysis of the lower and subsequently the upper extremities. During this same period, signs of heart failure develop (tachycardia, piercing pain in The Heart region). Biochemical disturbances in vitamin B₁ deficiency manifest as a negative nitrogen balance, elevated urinary excretion of Amino Acids and creatine, and the accumulation of alpha-keto acids and pentose sugars in the Blood and tissues. The content of thiamine and TPP in the heart Muscle and liver of beriberi patients is 5–6 times lower than normal.

Biological role. It has been experimentally proven that vitamin B₁ in the form of TPP is an essential component of at least 5 Enzymes involved in Intermediary METABOLISM. TPP is part of two complex enzyme systems—the Pyruvate and alpha-ketoglutarate dehydrogenase complexes—which catalyze The oxidative decarboxylation of pyruvic and alpha-ketoglutaric acids. As a constituent of transketolase, TPP participates in The transfer of a glycoaldehyde moiety from ketoses to aldoses (see Chapter 10). TPP serves as a coenzyme for Yeast pyruvate decarboxylase (during Alcoholic Fermentation) and gamma-hydroxyketoglutarate dehydrogenase.

These Examples most likely do not exhaust the BIOLOGICAL FUNCTIONS OF thiamine. In particular, TPP participates in the Oxidative Decarboxylation of glyoxylate and alpha-keto acids formed during The breakdown of branched-chain amino acids; in plants, TPP acts as an essential cofactor in the synthesis of valine and leucine as part of the enzyme acetolactate synthase.

Occurrence in nature and daily requirement. Vitamin B₁ is widely distributed in nature. Humans obtain the bulk of it from plant-based foods. Vitamin B₁ is abundant in yeast, whole-wheat brown bread, cereal seed coats and germs, soybeans, beans, and peas, and is present in smaller amounts in potatoes, carrots, and cabbage. Among animal products, the liver, Kidneys, and brain are the richest in vitamin B₁. Certain Bacteria inhabiting the animal intestine are capable of synthesizing sufficient amounts of thiamine; for example, The amount of vitamin B₁ synthesized by the gut microflora of cows proves entirely adequate to meet the Organism's requirements. The recommended daily intake levels of thiamine for various population groups, established by the RAMN Institute of Nutrition, range from 1.2 to 2.2 mg.