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

2. Absorption of pyridoxine
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Transport of pyridoxamine
II.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Tissue storage
The total body pools of vitamin B6 in an adult is estimated to be mg, constituting a supply sufficient to satisfy the body’s needs for 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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Metabolism of pyridoxine
III.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16. Interconversion of vitamers
Alkaline phosphatases
Phosphorylated forms of the vitamin can be dephosphorylated by membrane-bound alkaline phosphatases in:
Brain
Intestine
Liver
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

20. Catabolism FAD dependent aldehyde (pyridoxal) oxidase
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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

22. Effects of INH It does so by binding the vitamin directly.
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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

23. Effects of benzodiazepine and theophylline
Pyridoxal kinase binds the antianxiety drug benzodiazepine and can be inhibited by the antiasthmatic drug theophylline.
Short-term theophylline therapy induces biochemical signs of vitamin B6 deficiency due to this effect.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

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

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.
November 24, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

26. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
November 24, 2018