Absorption, transport and metabolism of thiamin

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

2. Absorption of thiamin
I.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Transport of thiamin
II.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Cellular uptake
Mutations in the transporter
gene are associated with the
condition called thiamin-
responsive megaloblastic
anemia (TRMA).
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Metabolism of thiamin
III.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. Thiamin is phosphorylated in the tissues
by two enzymes:
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14
Thiamin diPhosPhate (TPP)
Thiamin TriphosPhate (TTP)

15. Phosphorylation
Each of these esters
is catabolized by
thiamin
pyrophosphatase
which yields the
monophosphorylated
product thiamin
monophosphate
(TMP).
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15

16. 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.
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. Catabolism
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17

18. Urinary excretion
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
18

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
April 15, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
19

20. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 15, 2018 20