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
transport mechanisms 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/day for adult) of vitamin C is
high, 80-90%, and declines markedly at
vitamin C doses greater than about 1 g.
• The reduced and oxidized forms of the
vitamin are absorbed by different
mechanisms of active transport that occur
throughout the small intestine.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
4

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 unitransport of Na+, allowing that
ion to leak from cells.
• The SVCT is noncompetitively 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 acid and
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 predominantly in 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
mg or more.
• Plasma ascorbic acid levels in healthy adults are
typically 30-70 µmol/L and appear to be affected
by body fat distribution.
4/13/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
8

9. Cellular uptake
Cells accumulate in ascorbic acid to levels 5- to 100-
fold those of plasma.
Human cells become saturated at intakes of about
100 mg/day.
Mechanisms of cellular uptake of vitamin C are the
same as those responsible for its enteric 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
vitamin C transporters (SVCT1 and SVCT2)
•SVCT1 is expressed 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,
including some that lack ascorbic acid-
dependent enzymes.
Certain cell types (peripheral mononuclear
leukocytes) can accumulate concentrations as
great as several millimolar.
Tissue levels are 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 concentration in 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
successive losses of single electrons.
• The first monovalent oxidation results in the
formation of the ascorbyl free radical.
• The ascorbyl radical forms a reversible
electrochemical couple with ascorbic acid, but
can be further oxidized 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 CO2 and 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.
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19. Ascorbic acid regeneration goes by:
recycling of the ascorbic acid-
dehydroascorbic acid redox couple
glutathione (GSH) or dihydrolipoic acid
reduction of dehydroascorbic acid
enzymatic reduction of ascorbyl radical
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 through the glomeruli
and to be actively reabsorbed in the tubules by a saturable,
carrier-mediated process.
Little ascorbic acid is excreted in the urine of
humans consuming less than 100 mg/day.
Only one-fourth of the dose is excreted at
twice that intake.
At doses greater than about 500 mg/day, virtually all ascorbic
acid above that level is excreted unchanged in the urine, thus
producing no further increases 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
ascorbic acid to oxalic acid within 24 hours.
The excretion of oxalate is relevant to risk of
renal stone formation.
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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