1. Absorption, transport and metabolism of thiamin
Domina Petric, MD

2. Absorption of thiamin I.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3. Two means of uptake
Thiamin released by the action of phosphatase and pyrophosphatase in the upper small intestine is absorbed in two ways.
At low luminal concentrations (<2 µM) the process is carrier-mediated.
At higher concentrations (2.5 mg dose) passive diffusion also occurs.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4. Two means of uptake
The active transport mechanism is greatest in the proximal regions of the small intestine.
The cells of the intestinal mucosa have a thiamin pyrophosphokinase activity, with a Km about the same as that of the carrier-mediated absorption process.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Two means of uptake
Most of the thiamin present in the intestinal mucosa is in phosphorylated form.
Thiamin arriving on the serosal side of the intestine is largely in the free (nonphosphorylated) form.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6. Transport of thiamin II.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7. Thiamin bound to serum proteins
Most of the thiamin in serum is bound to proteins, mostly albumin.
About 90% of the total thiamin in blood (5-12 µg/dl) is in erythrocytes.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8. Cellular uptake
Thiamin is taken up by cells of the blood and other tissues by active transport.
Intracellular thiamin occurs predominantly (80%) in phosphorylated form, most of which is bound to proteins.
Thiamin uptake and secretion is mediated mostly by a soluble thiamin transporter that is dependent on Na+ and a transcellular proton gradient.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9. Cellular uptake
The transporter has been cloned and mapped to the human chromosome 1q24.
The greatest amounts of the transporter have been found in skeletal muscle, heart and placenta.
Low or non detectable amounts of transporter have been found in liver, kidney, brain and intestine.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10. Cellular uptake
Mutations in the transporter gene are associated with the condition called thiamin-responsive megaloblastic anemia (TRMA).
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Tissue distribution
The adult human stores 25 to 30 mg thiamin, most of which is in skeletal muscle, heart, brain, liver and kidneys.
Plasma, milk, and cerebrospinal fluid, and probably all extracellular fluids, contain free (unesterified) thiamin and thiamin monophosphate (TMP), which, unlike the more highly phosphorylated forms (thiamin diphosphate and thiamin triphosphate), appear capable of crossing cell membranes.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12. Tissue distribution
In infants, blood thiamin levels decline after birth, owing initially to a decrease in free thiamin, followed by a decrease in phosphorylated forms.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Metabolism of thiamin III.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

14. Thiamin is phosphorylated in the tissues by two enzymes:
Thiamin pyrophosphokinase catalyzes the formation of TPP using ATP.
TTP-ATP phosphoryltransferase catalyzes the formation of TTP from TPP and ATP.
Thiamin diPhosPhate (TPP) Thiamin TriphosPhate (TTP)
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

15. Phosphorylation
Each of these esters is catabolized by thiamin pyrophosphatase which yields the monophosphorylated product thiamin monophosphate (TMP).
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16. Thiamin in excess of that which binds in tissues is rapidly excreted.
Catabolism
The turnover of thiamin varies between tissues, but it is generally high.
Thiamin in excess of that which binds in tissues is rapidly excreted.
With an estimated half-life of 10 to 20 days in humans, thiamin deficiency states can deplete tissue stores within a couple of weeks.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

17. Catabolism
Declines in tissue thiamin levels are thought to involve enhanced degradation of TPP-dependent enzymes in the absence of the vitamin.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

18. Urinary excretion
Thiamin is excreted in the urine, chiefly as free thiamin and thiamin monophosphate, but also in small amounts as the diphosphate ester and other metabolites.
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

19. Thiamin metabolites thiochrome thiamin disulfide thiamin acetic acid
2-methyl-4-amino-5-pyrimidine carboxylic acid
4-methylthiazole-5-acetic acid
2-methyl-4-aminopyrimidine-5-carboxylic acid
2-methyl-4-amino-5-hydroxymethylpyrimidine
5-(2-hydroxyethyl)-4-methylthiazole
3-(2′-methyl-4-amino-5′-pyrimidinylmethyl)-4 methylthiazole-5-acetic acid
2-methyl-4-amino-5-formylaminomethylpyrimidine
February 25, 2019
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

20. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
February 25, 2019