10.31 Thiamin Functions

There are three functions of thiamin¹:

1. Cofactor for decarboxylation reactions (TPP)

2. Cofactor for the synthesis of pentoses (5-carbon sugars) and NADPH (TPP)

3. Membrane and nerve conduction (Not as a cofactor)

Decarboxylation Reactions

A decarboxylation reaction is one that results in the loss of carbon dioxide (CO2) from the molecule as shown below.

Figure 10.311 Decarboxylation reaction²

The transition reaction and one reaction in the citric acid cycle are decarboxylation reactions that use TPP as a cofactor. The figure below shows the transition reaction and citric acid cycle.

Figure 10.312 The transition reaction and citric acid cycle³

As shown below the conversion of pyruvate to acetyl CoA in the transition reaction is a decarboxylation reaction that requires TPP as a cofactor. CO2 (circled) is produced as a result of this reaction.

Figure 10.313 The transition reaction requires TPP as a cofactor

A similar TPP decarboxylation reaction occurs in the citric acid cycle converting alpha-ketoglutarate to succinyl-CoA. CO2 (circled) is given off as a result of this reaction.

Figure 10.314 Alpha-ketoglutarate dehydrogenase requires TPP as a cofactor

TPP also functions as a cofactor for the decarboxylation of valine, leucine, and isoleucine (branched-chain amino acids)¹.

Synthesis of Pentoses and NADPH

TPP is a cofactor for the enzyme transketolase. Transketolase is a key enzyme in the pentose phosphate (aka hexose monophosphate shunt) pathway. This pathway is important for converting 6-carbon sugars into 5-carbon sugars (pentose) that are needed for synthesis of DNA, RNA, and NADPH. In addition, pentoses such as fructose are converted to forms that can be used for glycolysis and gluconeogenesis⁴. Transketolase catalyzes multiple reactions in the pathway as shown below.

Figure 10.315 Transketolase in the pentose phosphate pathway uses TPP as a cofactor⁵

Membrane and Nerve Conduction

In addition to its cofactor roles, thiamin, in the form of thiamin triphosphate (TTP, 3 phosphates), is believed to contribute in some unresolved way to nervous system function1.

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

2. https://commons.wikimedia.org/wiki/File:Decarboxylation_reaction.png

3. http://en.wikipedia.org/wiki/File:Citric_acid_cycle_with_aconitate_2.svg

4. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.

5. https://commons.wikimedia.org/wiki/File:PPP_(en).svg