Absorption, transport and metabolism of pantothenic acid

Absorption, transport and metabolism of pantothenic acid in the human body

1. Absorption, transport and
metabolism of pantothenic acid
Domina Petric, MD

2. Absorption of pantothenic acid
I.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2

3. Hydrolysis of coenzyme forms
Pantothenic acid occurs in most foods and
feedstuffs as CoA and the acyl-carrier protein(ACP).
The utilization of the vitamin in foods depends on
thehydrolytic digestion of these protein complexes
torelease the free vitamin.
Both CoA and ACP aredegraded in the
lumen of the intestine to release the
vitamin as 4´-phosphopantetheine.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. Hydrolysis of coenzyme forms
4´-phosphopantetheineis
dephosphorylated to yield
pantetheine, whichis rapidly
converted by the intestinal
pantetheinaseto pantothenic acid.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Carrier-mediated uptake
Pantothenic acid is absorbed by a saturable, Na
+
-
dependent, energy-requiring process that shows
highest rates in the jejunum.
At high levels, it is alsoabsorbed by simple diffusion
throughout the smallintestine.
The alcohol form, panthenol, which isoxidized to
pantothenic acid in vivo, appears to beabsorbed
somewhat faster than the acid form.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Transport of pantothenic acid
II.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. Free in plasma
Pantothenic acid is transported in both the
plasmaand erythrocytes.
Plasma contains the vitamin onlyin the
free acid form, which erythrocytes take up
by passive diffusion.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. Free in plasma
•While erythrocytes carry some ofthe
vitamin unchanged, they convert
some of thevitamin to
4'-phosphopantothenic acid and
pantetheine.
•Erythrocytes carry most of the
vitamin in theblood.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. Cellular uptake
•Pantothenic acid is transported into other cells
in itsfree acid form by a Na
+
co-transporter.
•The pantothenic acid transport also appears to
transport biotin and to be influenced by
hormonalstatus, and to be mediated by protein
kinase C andcalmodulin.
•Upon cellular uptake, most of the vitamin is
converted to CoA, the predominant tissue form.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Tissue distribution
•The greatest concentrations of CoA are
found inthe liver, adrenals, kidneys,
brain, heart and testes.
•Much of this (70% in liver and 95% in
heart) islocated in the mitochondria.
•Tissue CoA concentrations are not
affected by deprivation of the vitamin.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. Tissue distribution
•Pantothenicacid is reabsorbed by
active transport.
•At higher concentrations, tubular
secretion of pantothenic acidoccurs.
•Tubular reabsorption appearsto be
the only mechanism for conserving
free pantothenic acid in the plasma.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. Tissue distribution
•Pantothenic acid istaken up in the choroid plexus
by a specific transportprocess, which, at low
concentrations of the vitamin involvesthe partial
phosphorylation of the vitamin.
•The cerebrospinal fluid, because it is constantly
renewed in the central nervous system, requires a
constant supply of pantothenic acid.
•Pantothenic acid isas CoA,involved in the
synthesis of the neurotransmitteracetylcholine
in brain tissue.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Metabolism of pantothenic acid
III.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. Coenzyme A biosynthesis
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14

15. In the cytosol
First step
Pantothenate kinase catalyzes
the ATP-dependent
phosphorylation of
pantothenic acid to yield
4'-phosphopantothenic acid.
This isthe rate-limiting step
in CoA synthesis.Under
normal conditions, it
appears to function far
below its maximalcapacity.
Inhibition by CoAesters
appears to be reversed by
carnitine. Theethanol
metabolite acetaldehyde also
inhibits theconversion of
pantothenic acid to CoA.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15
It can be inducedand appears to
be feedback inhibited by
4'-phosphopantothenic acid, CoA
esters (acetylCoA, malonyl-CoA
andpropionyl-CoA) andmore
weakly by CoA and long-chain
acyl-CoAs.

16. In the cytosol
Phosphopantothenylcysteine
synthase catalyzes the ATP-
dependent condensation of
4'-phosphopantothenic acid with
cysteine to yield
4´-phosphopantothenylcysteine.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. In the cytosol
•Phosphopantothenylcysteine
decarboxylase catalyzes the
decarboxylation of
4'-phosphopantothenylcysteine to
yield 4'-phosphopantetheinein the
cytosol, whereupon it is transported
into the mitochondria.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17

18. In the mitochondrial inner membrane
Phosphopantetheine
adenyltransferase catalyzes the
ATP-dependent adenylation of
4‘-phosphopantetheine to CoA
to yield dephospho-CoA.
Because this reaction is
reversible, at low ATP
levels dephospho-CoA can
be degraded to yield ATP.
Dephospho-CoA
kinase catalyzes
the ATP
dependent
phosphorylation
of dephospho-
CoAto yield CoA.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
18

19. Acyl-Carrier Protein biosynthesis
•The acyl-carrier protein (ACP) is synthesized as
the apoproteinlacking the prosthetic group.
•Thatgroup, 4'-phosphopantetheine, is
transferred to ACPfrom CoA by the action of
4'-phosphopantetheineapoACP transferase.
•The prosthetic groupis bound to the apo-ACP
via a phosphoesterlinkageat a serinylresidue.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
19

20. Catabolism of Coenzyme Aand ACP
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
20

21. Excretion
•The vitamin is excreted mainly in the
urineas free pantothenic acid, as well as
some 4'-phosphopantethenate.
•The renal tubular secretion of
pantothenic acidresults in urinary
excretion of thevitamin correlating with
dietary intake.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
21

22. Excretion
•An appreciable amount (∼15% of daily
intake) is oxidizedcompletely and is
excreted across the lungs as CO
2.
•Humans typically excrete in the urine
0.8–8.4 mg ofpantothenic acid per day.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
22

23. Literature
•Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
April 17, 2018 23