Absorption, transport and metabolism of pyridoxine

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

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

3. Diffusion linked to phosphorylation
• The various forms of vitamin B6 are
absorbed via passive diffusion
primarily in the jejunum and ileum.
• The enteric absorption of pyridoxal
phosphate and pyridoxamine phosphate
involves their obligate
dephosphorylation catalyzed by a
membrane-bound alkaline
phosphatase.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. Diffusion linked to phosphorylation
• Those products and the
nonphosphorylated vitamers in the
digesta are absorbed by diffusion driven
by trapping of the vitamin as
5′-phosphates through the action of
phosphorylation by a pyridoxal kinase in
the jejunal mucosa.
• Pyridoxine and pyridoxamine that have
been trapped are then oxidized to
pyridoxal phosphate in that tissue.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Transport of pyridoxamine
II.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. Plasma vitamin B6
• Only a small portion (<0.1%) of total body
vitamin B6 is present in blood plasma.
• Pyridoxal phosphate comprises more than
90% of the vitamin in plasma bound to
albumin, which protects it from
hydrolysis.
• Most of the vitamer in plasma is derived
from the liver after metabolism by
hepatic flavoenzymes.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. Plasma vitamin B6
• The plasma pyridoxal phosphate
concentration typically is less than 1 mmol.
• Smaller amounts of other vitamers
are also found.
• The circulating vitamin is tightly bound
to proteins (primarily albumin in the
plasma and hemoglobin in
erythrocytes) via Schiff base linkages.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. Plasma vitamin B6
Plasma pyridoxal phosphate
concentrations decline during pregnancy.
Renal failure has been found to reduce
the plasma pyridoxal phosphate level.
Submaximal exercise has been shown to
increase it.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. Role of phosphorylation in tissue
uptake
• Pyridoxal crosses cell membranes more
readily than pyridoxal phosphate.
• After being taken into the cell, the
vitamin is again phosphorylated by
pyridoxal kinase to yield the predominant
tissue form, pyridoxal phosphate.
• Small quantities of vitamin B6 are stored
in the body, mainly as pyridoxal
phosphate but also as pyridoxamine
phosphate.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Role of phosphorylation in tissue
uptake
• The greatest levels are found in
the liver, brain, kidney, spleen
and muscle, where the vitamin
is bound to various proteins.
• In muscle, pyridoxal phosphate
is bound mostly to glycogen
phosphorylase.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. Tissue storage
• The total body pools of vitamin B6 in an
adult is estimated to be 40-150 mg,
constituting a supply sufficient to satisfy the
body’s needs for 20-75 days.
• This amount is composed of two pools: one
with a rapid (0.5 day) turnover and a
second with a longer (25-33 days)
turnover.
• Muscle contains most (70-80%) of the body’s
vitamin B6, in the form of pyridoxal 5′-
phosphate bound to glycogen
phosphorylase.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. Exercise
Moderate exercise has been found
to increase plasma pyridoxal
phosphate concentrations by 23%
within 20 min.
This appears to be related to the
increased need for
gluconeogenesis, which results in
the release of pyridoxal phosphate
from glycogen phosphorylase.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

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

14. Interconversion of vitamers
• The vitamers B6 are readily interconverted
metabolically by reactions involving
phosphorylation/dephosphorylation,
oxidation/reduction and
amination/deamination.
• The nonphosphorylated vitamers cross
membranes more readily than their
phosphorylated analogs.
• Phosphorylation is important for retaining
the vitamin intracellularly.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14

15. Interconversion of vitamers
Pyridoxal kinase
• This hepatic enzyme catalyzes the
phosphorylation of pyridoxine, pyridoxal and
pyridoxamine, yielding the corresponding
phosphates.
• It requires a zinc-ATP complex, the formation
of which is facilitated by zinc-
metallothioneine (MT), and is stimulated by
potassium ion.
• The role of MT in pyridoxal kinase activity
suggests that zinc status may be important in
the regulation of vitamin B6 metabolism.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15

16. Interconversion of vitamers
Alkaline phosphatases
Phosphorylated forms of the vitamin can
be dephosphorylated by membrane-
bound alkaline phosphatases in:
• Brain
• Intestine
• Liver
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. Interconversion of vitamers
Pyridoxamine phosphate oxidase
• This enzyme catalyzes the limiting step
in vitamin B6 metabolism.
• It requires flavin mononucleotide (FMN).
• Deprivation of riboflavin may reduce
the conversion of pyridoxine and
pyridoxamine to the active coenzyme
pyridoxal phosphate.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17

18. Interconversion of vitamers
Pyridoxal dehydrogenase
The reduced forms (pyridoxine or
pyridoxol phosphate) can be
oxidized by pyridoxal
dehydrogenase to yield pyridoxal or
pyridoxal phosphate, either of
which can be aminated by
transaminases.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
18

19. Interconversion of vitamers
The liver is the central organ for
vitamin B6 metabolism,
containing all of the enzymes
involved in its interconversions.
The major forms of the vitamin
in that organ are pyridoxal
phosphate and pyridoxamine
phosphate.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
19

20. Catabolism
Pyridoxal phosphate is dephosphorylated
and oxidized primarily in the liver by:
• FAD dependent aldehyde (pyridoxal)
oxidase
• NAD-dependent aldehyde
dehydrogenase
To yield 4-pyridoxic acid.
• Pyridoxic acid is excreted in the urine.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
20

21. Effects of alcohol
• Several drugs can antagonize vitamin B6.
• Alcohol´s degradation product,
acetaldehyde, displaces pyridoxal
phosphate from proteins, resulting in
enhanced catabolism of the coenzyme.
• Acetaldehyde also stimulates the activity of
alkaline phosphatase, enhancing the
dephosphorylation of pyridoxal
phosphate.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
21

22. Effects of INH
The antituberculotic drug
isonicotinic acid hydrazide (INH)
also antagonizes vitamin B6.
It does so by binding the
vitamin directly.
Vitamin B6 must be given to
patients treated with INH.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
22

23. Effects of benzodiazepine and
theophylline
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
23

24. Excretion
The products of vitamin
B6 metabolism are
excreted in the urine,
the major one being
4-pyridoxic acid.
It has been estimated
that humans oxidize
40-60% of ingested
vitamin B6 to
4-pyridoxic acid.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
24

25. Excretion
• Urinary levels of 4-pyridoxic acid are
inversely related to protein intake.
• This effect appears to be greater for
women than for men.
• 4-pyridoxic acid is not detectable in the
urine of vitamin B6-deficient subjects,
making it useful in the clinical
assessment of vitamin B6 status.
April 17, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
25

26. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 17, 2018 26