Companion Animals: Thiamin

Functions

A principal function of thiamin in all cells is as the coenzyme cocarboxylase or TPP. The tricarboxylic acid cycle (TCA; citric acid cycle; Krebs cycle) is responsible for production of energy in the body. In this cycle, breakdown products of carbohydrates, fats and proteins are brought together for further breakdown and for synthesis. The vitamins riboflavin, pantothenic acid and niacin, as well as thiamin, play roles in the cycle. Thiamin is the coenzyme for all enzymatic decarboxylations of alpha-keto acids. Thus, it functions in the oxidative decarboxylation of pyruvate to acetate, which in turn is combined with coenzyme A (CoA) for entrance into the TCA cycle.

Thiamin is essential in two oxidative decarboxylation reactions in the TCA cycle that take place in cell mitochondria and one reaction in the cytoplasm of the cells (Figure 1). These reactions are essential for utilization of carbohydrates to provide energy. Decarboxylation in the TCA cycle removes carbon dioxide, and the substrate is converted into the compound having the next lower number of carbon atoms:

Pyruvate ---> acetyl-CoA + CO2

alpha-Ketoglutaric acid ---> succinyl-CoA + CO2

Thiamin plays a very important role in glucose metabolism. Thiamin pyrophosphate is a coenzyme in the transketolase reaction that is part of the direct oxidative pathway (pentose phosphate cycle) of glucose metabolism occurring in the cell cytoplasm of liver, brain, adrenal cortex and kidney, but not skeletal muscle. The pentose phosphate cycle is the only mechanism known for synthesis of ribose, which is needed for nucleotide formation. This cycle also results in the reduction of nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for reducing intermediates from carbohydrate metabolism during fatty acid synthesis.

Little is known of thiamin functions in nervous tissue. However, evidence has accumulated for a specific role of thiamin in neurophysiology that is independent of its coenzyme function. The possible mechanism of action of thiamin in nervous tissue includes the following (Muralt, 1962; Cooper et al., 1963): (a) thiamin is involved in the synthesis of acetylcholine, which transmits neural impulses; (b) thiamin participates in the passive transport of sodium (Na+) to excitable membranes, which is important for the transmission of impulses at the membrane of ganglionic cells; and (c) thiamin's role in glucose metabolism, via pentose phosphate pathways and pyruvate dehydrogenase complex, influences the efficiency of energy metabolism and synthesis of fatty acids in the nervous system.

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