10.3: Thiamin

Thiamin (Vitamin \(B_1\)) structurally consists of 2 rings that are bridged together as shown below.

Figure \(\PageIndex{1}\): Structure of thiamin1

Since it was one of the original vitamins, (remember it was the primary part of Factor B), it was originally named thiamine (consistent with vitamine). The -e has since been dropped in its spelling. Thiamin is sensitive to heat, so prolonged heating causes the cleavage of thiamin between the 2 rings destroying its activity2.

Like most of the B vitamins, thiamin's primary function is as a cofactor for enzymes. It is not thiamin alone that serves as a cofactor but instead thiamin diphosphate (thiamin + 2 phosphates), which is more commonly referred to as thiamin pyrophosphate (TPP). The structure of thiamin pyrophosphate is shown below.

Figure \(\PageIndex{2}\): Structure of thiamin pyrophosphate (aka thiamin diphosphate)3

In plants, thiamin is found in its free form, but in animals it is mostly thiamin pyrophosphate. These phosphates must be cleaved before thiamin is taken up into the enterocyte4.

Thiamin uptake and absorption is believed to be an efficient process that is passive when thiamin intake is high and active when thiamin intakes are low4. There are two thiamin transporters (THTR), THTR1 and THTR2, that are involved in thiamin uptake and absorption. THTR1 is found on the brush border and basolateral membrane, while THTR2 is only found on the brush border membrane as shown below5.

Figure \(\PageIndex{3}\): Thiamin uptake and absorption

Like most water-soluble vitamins there is little storage of thiamin.

Query \(\PageIndex{1}\)

Thiamin Functions

There are three functions of thiamin4:

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 (\(\ce{CO2}\)) from the molecule as shown below.

Figure \(\PageIndex{4}\): Decarboxylation reaction6

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 \(\PageIndex{5}\): The transition reaction and citric acid cycle7

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

Figure \(\PageIndex{6}\): The transition reaction requires TPP as a cofactor7

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

Figure \(\PageIndex{7}\): Alpha-ketoglutarate dehydrogenase requires TPP as a cofactor7

TPP also functions as a cofactor for the decarboxylation of valine, leucine, and isoleucine (branched-chain amino acids)4.

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 gluconeogenesis8. Transketolase catalyzes multiple reactions in the pathway as shown below.

Figure \(\PageIndex{8}\): Transketolase in the pentose phosphate pathway uses TPP as a cofactor9

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 function6.

Query \(\PageIndex{2}\)

Thiamin Deficiency & Toxicity

Thiamin deficiency is rare in developed countries, but still occurs in poorer countries where white (aka polished) rice is a staple food. During the polishing process, thiamin, and many other nutrients, are removed. Some people also have a mutation in THTR1 that causes them to become thiamin deficient10. Thiamin deficiency is known as beriberi, which, when translated, means "I can't, I can't." The symptoms of beriberi are illustrated in the link below.

There are two major forms of beriberi: dry and wet. Dry beriberi affects the nervous system, with symptoms such as loss of muscle function, numbness, and/or tingling. Wet beriberi affects the cardiovascular system resulting in pitting edema, along with enlargement of the heart10. A picture of a person with beriberi is shown below.

Figure \(\PageIndex{9}\): A person suffering from beriberi11

Query \(\PageIndex{3}\)

Another group that is at risk for thiamin deficiency is alcoholics. There are three reasons why alcoholics are prone to becoming deficient12:

1. Alcohol displaces foods that are better sources of thiamin
2. Liver damage decreases TPP formation
3. Increased thiamin excretion

The thiamin deficiency found in alcoholics is known as Wernicke-Korsakoff Syndrome. Symptoms of this condition include paralysis or involuntary eye movement, impaired muscle coordination, memory loss and confusion3. The following video shows some of the symptoms of this condition.

Video \(\PageIndex{1}\): Wernicke-Korsakoff Syndrome (First 1:50). https://www.youtube.com/watch?v=wDcyBXJAZNM

Thiamin toxicity has never been reported as a result of oral intake. Thus, there is little worry about thiamin toxicity13.

Query \(\PageIndex{4}\)

References

1. en.Wikipedia.org/wiki/File:Thiamin.svg
2. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw's perspectives in nutrition. New York, NY: McGraw-Hill.
3. en.Wikipedia.org/wiki/File:Th...iphosphate.png
4. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
5. Said H, Mohammed Z. (2006) Intestinal absorption of water-soluble vitamins: An update. Curr Opin Gastroenterol 22(2): 140-146.
6. https://en.Wikipedia.org/wiki/Decarboxylation#/media/File:Decarboxylation_reaction.png
7. https://en.Wikipedia.org/wiki/Citric_acid_cycle#/media/File:Citric_acid_cycle_with_aconitate_2.svg
8. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.
9. commons.wikimedia.org/wiki/File:PPP_(en).svg
10. http://www.nlm.nih.gov/medlineplus/e...cle/000339.htm
11. en.Wikipedia.org/wiki/File:Beriberi_USNLM.jpg
12. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
13. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.