Absorption, transport and metabolism of vitamin C

Absorption, transport and metabolism of vitamin C

1. Domina Petric, MD
Absorption, transport and metabolism of vitamin C

2. Absorption of vitamin C
I.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
2

3. Absorption of vitamin C
Humans do not synthesize ascorbic
acid, but absorb the vitamin by:
•passive diffusion important at high doses
•saturable, carrier-mediated, active
transportmechanisms important at low
doses
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
3

4. Absorption of vitamin C
•The efficiency of absorption of physiological
doses (≤180 mg/dayforadult) of vitamin C is
high, 80-90%,and declines markedly at
vitamin C doses greaterthan about 1 g.
•The reduced and oxidized forms ofthe
vitamin are absorbed by different
mechanismsof active transport that occur
throughout the smallintestine.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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5. Ascorbic acid uptake by the sodium-
dependent vitamin C transporter (SVTC)
•This carrier moves L-ascorbic acid by an
electrogenic, Na
+
dependent process with a
stoichiometric ratio of two Na
+
ions per ascorbic
acid molecule.
•In the absence of ascorbic acid,the SVCT can
facilitate the unitransportof Na
+
,allowing that
ion to leak from cells.
•The SVCTisnoncompetitively inhibited by
flavonoids.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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6. Dehydroascorbic acid uptake by glucose
transporters
•The uptake of dehydroascorbic acid is 10-to
20-fold faster than that of ascorbic acidand
involves isoforms of the glucose transporter,
GLUT1, GLUT3 and perhaps GLUT4.
•Upon entry into the cell, dehydroascorbic acid
is quickly reduced to ascorbic acid, probably
by glutaredoxine reductase and/or reduced
glutathione (GSH).
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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7. Transport of vitamin C
II.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
7

8. Transport predominantlyin reduced form
•Vitamin C is transported in the plasma
predominantly (80-90%) in the reduced form,
ascorbic acid.
•Plasma ascorbic acid shows a sigmoid
relationship with the level of vitamin C intake,
saturation being achieved at daily doses of 1000
mgor more.
•Plasma ascorbic acid levels in healthyadultsare
typically 30-70 µmol/L and appear to beaffected
by body fat distribution.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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9. Cellular uptake
Cells accumulate inascorbic acid to levels 5-to 100-
fold those of plasma.
Human cells become saturated at intakes of about
100 mg/day.
Mechanismsof cellular uptake ofvitamin C are the
same as those responsible for itsenteric absorption.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
9

10. Cellular uptake mechanisms
Ascorbic acid uptake by sodium-dependent
vitaminC transporters (SVCT1 and SVCT2)
•SVCT1 isexpressed in epithelial tissues
including the intestine, liver and kidney.
•SVCT2 is expressed in brain,lung, heart,
eye, placenta, in neuroendocrine,
exocrine and in endothelial tissues.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
10

11. Cellular uptake mechanisms
Dehydroascorbic acid transport by glucose transporters
(GLUT1, GLUT3, GLUT4)
•By interacting at the level of these transporters, insulin
can promote the cellular uptake of dehydroascorbic acid.
•By competing for uptake by the transporter,
physiological levels of glucose can inhibit
dehydroascorbic acid uptake by several cell types:
adipocytes, erythrocytes, granulose cells, neutrophils,
osteoblasts and smooth muscle cells.
•Diabetic patients can have abnormally high
plasma levels of dehydroascorbic acid.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
11

12. Tissue distribution
Nearly all tissues accumulate vitamin C,
includingsome that lack ascorbic acid-
dependent enzymes.
Certain cell types (peripheralmononuclear
leukocytes) can accumulate concentrations as
great as several millimolar.
Tissue levelsare decreased by virtually all
forms of stress.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
12

13. Ascorbic acid concentrationin tissues
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
13
Tissue Ascorbic acid (mg/100 g)
Adrenals 30-40
Pituitary 40-50
Liver 10-16
Thymus 10-15
Lungs 7
Kidneys 5-15
Heart 5-15
Muscle 3-4
Brain 3-15
Pancreas 10-15
Lens 25-31
Plasma 0,4-1

14. Metabolism of vitamin C
III.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
14

15. Oxidation
•Ascorbic acid is oxidized in vivo by two
successivelosses of single electrons.
•The first monovalentoxidation results in the
formation of the ascorbylfreeradical.
•The ascorbylradical forms a reversible
electrochemical couple with ascorbic acid,but
can be furtheroxidized irreversibly to
dehydro-L-ascorbic acid.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
15

16. Oxidation
Subsequent irreversible hydrolysis of
dehydroascorbic acid yields 2,3-diketo-L-
gulonic acid, which undergoes either:
•decarboxylation to CO
2and carbon
fragments: xylose, xylonic acid, lyxonic
acid
•or oxidation to oxalic acid and 4-C
fragments: threonic acid
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
16

17. Oxidation
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
17

18. 4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
18

19. Ascorbic acid regeneration goes by:
recycling of the ascorbic acid-
dehydroascorbic acid redox couple
glutathione (GSH)or dihydrolipoicacid
reduction of dehydroascorbic acid
enzymatic reduction of ascorbylradical
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
19

20. Excretion
Ascorbate is thought to pass unchanged throughthe glomeruli
and to be actively reabsorbed in thetubules by a saturable,
carrier-mediated process.
Littleascorbic acid is excreted in the urineof
humans consuming less than 100 mg/day.
Onlyone-fourth of the dose is excreted at
twice thatintake.
At doses greater than about 500 mg/day, virtually all ascorbic
acid above that levelis excreted unchanged in the urine, thus
producing nofurtherincreases in body ascorbate stores.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
20

21. Excretion
The epithelial cells of the renal tubules reabsorb
dehydroascorbic acid after it has been filtered from
the plasma.
Humans convert only 1.5% of ingested
ascorbicacid to oxalic acid within 24 hours.
Theexcretion of oxalate is relevant to risk of
renal stoneformation.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
21

22. Excretion
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
22
Ascorbic acid is also excreted in the
gastric juice,which typically has
levels three times that of plasma.
Notable exceptions are in patients
with atrophic gastritis or
Helicobacter pylori infection: low
gastric juice ascorbic acid.

23. •Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Literature
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